Mohamed Haidara - Academia.edu (original) (raw)

Papers by Mohamed Haidara

Archives of Physiology and Biochemistry, 2021

BACKGROUND The link between oxidative stress (ROS), apoptosis (p53) and fibrosis (collagen) in ty... more BACKGROUND The link between oxidative stress (ROS), apoptosis (p53) and fibrosis (collagen) in type 2 diabetes mellitus (T2DM)-induced cardiac injury in the presence and absence of the antidiabetic drug, metformin has not been investigated before. MATERIAL AND METHODS T2DM was induced in rats by a combination of high carbohydrate and fat diets (HCFD) and streptozotocin (50 mg/kg) injection. The protection group started metformin (200 mg/kg) treatment 14 days prior to the induction of diabetes and continued on metformin and HCFD until being sacrificed at week 12. RESULTS Diabetes significantly induced blood levels of ROS and left ventricular p53 and collagen expression that was inhibited by metformin. Metformin also significantly reduced glycated haemoglobin and dyslipidemia induced by diabetes. In addition, a significant correlation between ROS-p53-collagen axis and glycaemia and hyperlipidaemia was observed. CONCLUSIONS These findings show that metformin provides substantial protection against diabetic cardiomyopathy-induced ROS-p53 mediated fibrosis and dyslipidemia.

Mini-Reviews in Medicinal Chemistry, 2015

Neuroscience & Biobehavioral Reviews, 2015

Neurons are postmitotic cells that are in permanent cell cycle arrest. However, components of the... more Neurons are postmitotic cells that are in permanent cell cycle arrest. However, components of the cell cycle machinery that are expressed in Alzheimer's disease (AD) neurons are showing features of a cycling cell and those attributed to a postmitotic cell as well. Furthermore, the unique physiological operations taking place in neurons, ascribed to "core cell cycle regulators" are also key regulators in cell division. Functions of these cell cycle regulators include neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. In this review, we focus on cohesion and cohesion related proteins in reference to their neuronal functions and how impaired centromere/cohesion dynamics may connect cell cycle dysfunction to aneuploidy in AD.

Angiology, 2011

The role of inflammation is well established in the pathogenesis of atherosclerosis and an increa... more The role of inflammation is well established in the pathogenesis of atherosclerosis and an increased level of circulating inflammatory markers may predict the future risk of atherosclerosis progression and plaque rupture. C-reactive protein (CRP) identification by hypersensitive methods (high-sensitivity CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid endarterectomy (CEA) is a well-established procedure for carotid stenosis treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis reduction may be prevented by the anti-inflammatory effect of statins. This review considers the recent findings on the presence of hsCRP and C3 complement concentration and inflammatory plaque composition as well as their effects on ICA restenosis rate, following eversion CEA with emphasis on human studies.

Archives of Physiology and Biochemistry, 2019

Insulin protects against type 1 diabetes mellitus-induced aortopathy associated with the inhibiti... more Insulin protects against type 1 diabetes mellitus-induced aortopathy associated with the inhibition of biomarkers of vascular injury in rats', Archives of Physiology and Biochemistry.

Archives of Physiology and Biochemistry, 2019

Background: The potential inhibitory effects of captopril, the angiotensin-converting enzyme inhi... more Background: The potential inhibitory effects of captopril, the angiotensin-converting enzyme inhibitor, on thioacetamide (TAA)-induced hepatic mammalian target of rapamycin (mTOR), liver injury enzymes, blood pressure, and biomarkers of inflammation and oxidative stress have not been investigated before. Materials and methods: Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (model group) or were pretreated with captopril (150 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment (protective group). Results: Captopril significantly (p < .05) inhibited TAA-induced hypertension, liver tissue levels of mTOR, TIMP-1, TNF-a, IL-6, MDA; and blood levels of lipids, ALT, and AST. We further demonstrated a significant (p < .01) positive correlation between mTOR scoring and the levels of inflammatory, oxidative and liver injury biomarkers. Conclusions: Captopril protects against TAA-induced mTOR, liver injury enzymes, dyslipidemia, hypertension, inflammation, and oxidative stress.

International Journal of Morphology

Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead t... more Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis-mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

Archives of Physiology and Biochemistry, 2020

Background: We investigated whether the anti-inflammatory and antioxidant agent, resveratrol can ... more Background: We investigated whether the anti-inflammatory and antioxidant agent, resveratrol can inhibit type 2 diabetes mellitus (T2DM)-induced osteoarthritis (OA) in rats and whether it is associated with the suppression of glycaemia, dyslipidemia and inflammatory and oxidative stress biomarkers. Materials and methods: T2DM was induced by streptozotocin (50 mg/kg body weight) and high carbohydrate and fat diet (HCFD). The protective group was put on resveratrol (30 mg/kg) 14 days prior to the induction of diabetes and continued on resveratrol and HCFD until being sacrificed at week 12. Results: Diabetic rats showed a substantial damage to the knee joints and loss of proteoglycans from the articular cartilage, which were effectively but not completly protected by resveratrol. Resveratrol also significantly (p .0029) reduced diabetic up-regulation of HbA1c, hyperlipidaemia, inflammation and oxidative stress. Conclusions: Resveratrol protects against T2DM-induced OA associated with the inhibition of glycated haemoglobin, dyslipidemia, and biomarkers of oxidative stress and inflammation.

Naunyn-Schmiedeberg's Archives of Pharmacology

Ultrastructural Pathology, 2021

ABSTRACT Diabetes-induced osteoarthritis (OA) is a chronic inflammatory disease that damages the ... more ABSTRACT Diabetes-induced osteoarthritis (OA) is a chronic inflammatory disease that damages the cartilage in the joints and could lead to disability. The protective effect of the antioxidant and anti-inflammatory agent, resveratrol, against alterations to the knee articular cartilage ultrastructure induced by type 2 diabetes mellitus (T2DM) associated with the inhibition of dyslipidemia, oxidative stress, and inflammation has not been investigated before. Therefore, we modeled OA in rats 10 weeks post diabetic induction using a high carbohydrate and fat diet and a single injection of streptozotocin (50 mg/kg body weight), and the protective group of rats started resveratrol (30 mg/kg; orally) treatment 2 weeks before diabetic induction and continued on resveratrol until the end of the experiment at week 12. Blood chemistry analysis confirmed hyperglycemia (elevated glucose and glycated hemoglobin, HbA1c), dyslipidemia (elevated triglyceride, cholesterol, and low-density lipoprotein-cholesterol), and upregulation of oxidative stress (malondialdehyde) and inflammatory (C-reactive protein and tumor necrosis factor-α) biomarkers in the model group. In addition, using light and electron microscopy examinations, we also observed in the model group substantial damage to the articular cartilage and profound chondrocyte and territorial matrix ultrastructural alterations such as chondrocytes with degenerated nucleus and mitochondria, scarce cytoplasmic processes, and absence of the fine fibrillar appearance of territorial matrix. Resveratrol pretreatment significantly (p ≤ 0.0029) but not completely protected from T2DM-induced OA. We conclude that resveratrol protects against alterations to the articular cartilage ultrastructure induced secondary to T2DM in rats, which is associated with the inhibition of glycemia, hyperlipidemia, and biomarkers of oxidative stress and inflammation.

Current Pharmacology Reports, 2017

Purpose of Review Numerous studies have shown a positive correlation between serum Hcy level and ... more Purpose of Review Numerous studies have shown a positive correlation between serum Hcy level and various pathological conditions such as coronary, carotid, and peripheral vascular disease. Increased plasma Hcy levels are associated not only with an increased risk of arteriosclerosis but also with atherosclerosis and thrombosis. The aim of this review is to review biochemical mechanisms responsible for development and progression of cardiovascular diseases (CVD). Recent Findings A recent finding shows that cardiac tissue function improves in hyperhomocysteinemic (HHcy) patients after consumption of folic acid and cobalamin. Furthermore, in patients with HHcy plasma levels of nitric oxide (NO) and tetrahydrobiopterin were remarkably decreased compared with the normal individuals. Cardiac endothelial function and coronary flow velocity reserve were significantly disrupted in chronic HHcy patients compared with the control subjects. Summary Lowering elevated level of Hcy by supplementation with folic acid and B12 vitamin reduces plasma level of Hcy and substantially reduces the risk of CVD. The combination of consuming supplements of B12, B6, and folate on a daily basis reduces the progression of atherosclerosis, measured by the area of the carotid artery plaques and their administration, improve CVD and may slightly prevent the incidence of atherosclerotic vascular events. A correlation between Hcy and hypertension indicates that Hcy levels could be used as a potential marker for atherosclerosis progression.

Ultrastructural Pathology, 2019

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chond... more We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 μL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA +STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly (p < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.

Hypertension, 1999

The genes encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2, also known... more The genes encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2, also known as prostaglandin-endoperoxide synthase-2) are induced in many types of cells in response to proinflammatory cytokines. We have previously shown that interleukin-1␤ (IL) stimulates iNOS and COX-2 mRNA in cardiac myocytes. Because IL has been shown to activate mitogen-activated protein kinase (MAPK) signaling pathways in many different cells, we tested whether the p42/44 and p38 MAPK pathways were involved in IL stimulation of iNOS and COX-2, using a specific inhibitor of p42/44 activation, PD98059 (PD), and the p38 inhibitor SB205380 (SB). Nitrites were measured using the Griess reagent, prostaglandin PGE 2 by an enzyme immunoassay, iNOS and COX-2 protein by Western blot analysis, and iNOS mRNA by Northern blot analysis. Tested separately, the p38 kinase and MAPK inhibitors partially reduced IL stimulation of nitrite, iNOS protein, and iNOS mRNA; used together, they completely abolished the effect of IL. SB and PD inhibited IL-stimulated COX-2 protein by 60% and 80%, respectively, and IL-stimulated COX-2 protein was totally prevented by the combination of inhibitors. PGE 2 production was inhibited more than 99% by either drug alone, suggesting a posttranslational effect on enzyme activity. To test whether this posttranslational effect involved the cytosolic phospholipase A 2 (cPLA 2) isoform, Western blots were probed for cPLA 2 protein. Results indicated that IL stimulated cPLA 2 activity and synthesis, which was inhibited by SB but not PD. These data indicate that (1) IL induction of iNOS synthesis depends on both the p42/44 and p38 signaling pathways, acting primarily at the level of transcriptional regulation; and (2) IL regulation of COX-2 synthesis involves the p42/44 and p38 signaling pathways, with an additional level of regulation occurring posttranslationally, perhaps at the level of activation of the cPLA 2 isoform, which may be involved in intracellular signaling, as well as regulation of arachidonic acid release for COX-2 activity. (Hypertension. 1999;33[part II]:276-282.

Collection of Czechoslovak Chemical Communications, 2006

Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with ... more Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with almost a total loss of estrogenic activity, we studied the effects of some of these compounds on estrogen receptors (ER), the translocation of the estrogen-ER complexes formed in presence of competing substances into the nucleus, as well as the binding of these complexes to DNA. The results of uterotrophic effects of analysed derivatives are in agreement with the influence of these compounds on activity and binding parameters of estrogen receptors. Namely, compounds that show relatively high antiestrogenic activity predominantly increaseKdand inhibit translocation to nuclei of radioactive complexes formed in their presence. On the other hand, compounds that do not significantly change binding parameters of estrogen receptors do not show antiestrogenic effect inin vivoexperiments.

International Journal of Morphology, 2017

Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver f... more Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver failure are among the common public health problems. We sought to investigate the damage to the hepatocyte ultrastructure induced by high fat diets (HFD) and compared the therapeutic effects at the cellular level of two antioxidant and lipid lowering agents; Crataegus aronia extracts and simvastatin on hepatic steatosis. Rats were either fed with HFD (model group) or low fat diets (LFD) (control group) for 15 weeks before being sacrificed and therapeutic groups started the treatment with these agents after week 11 until the sacrifice day. Harvested liver tissues were examined using transmission electron microscopy (TEM) and liver homogenates were assayed for markers of antioxidative stress that are known to be modulated in liver injury. TEM examinations of the model group showed a profound damage to the hepatocytes compared to the control group as demonstrated by steatosis, damaged mitochondria and vaculated cytoplasm, disrupted rough and smooth endoplasmic reticulum and nuclear membrane, dilated intercellular space between hepatocytes, and alterations in lysosomes. In addition, HFD ameliorated the anti-oxidant glutathione (GSH) and augmented the oxidative stress TBARS biomarkers. Both Crataegus aronia and simvastatin significantly reduced lipids and TBARS, and treated damage to hepatic cells, but hepatocyte structures were differentially responded to these agents. However, only Crataegus aronia induced GSH (p=0.001). We conclude that HFD-induced hepatic steatosis caused a substantial damage to the hepatocyte's ultrastructures, and Crataegus aronia and simvastatin treatments differentially reversed hepatic injuries.

International Journal of Morphology, 2018

Metformin pretreatment ameliorates diabetic nephropathy induced by a combination of high fat diet... more Metformin pretreatment ameliorates diabetic nephropathy induced by a combination of high fat diet and streptozotocin in rats.

International Journal of Morphology, 2020

The potential inhibitory effect of the insulin mimicking agent, vanadium on type 2 diabetes melli... more The potential inhibitory effect of the insulin mimicking agent, vanadium on type 2 diabetes mellitus (T2DM)induced alterations to the aorta ultrastructure associated with the suppression of dyslipedima and biomarkers of inflammation has not been investigated before. Therefore, we tested whether vanadium can protect against aortic injury induced secondary to T2DM possibly via the inhibition of blood lipid and inflammatory biomarkers. T2DM was induced in rats by a high-fat diet and streptozotocin (50 mg/ kg), and the treatment group started vanadium treatment five days post diabetic induction and continued until being sacrificed at week 10. Using light and electron microscopy examinations, we observed in the model group substantial damage to the aorta tissue such as damaged endothelium, degenerative cellular changes with vacuolated cytoplasm and thickened internal elastic lamina that were substantially ameliorated by vanadium. Administration of vanadium to diabetic rats also significantly (p<0.05) reduced blood levels of glucose, hyperlipidemia and biomarkers of inflammation (TNF-a, IL-6). We conclude that vanadium protects against T2DM-induced aortic ultrastructural damage in rats, which is associated with the inhibition of blood sugar and lipid and inflammatory biomarkers.

International Journal of Morphology, 2020

Menopause complications such as cardiovascular and bone diseases represent a major public health ... more Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.

Diagnostics

Liver fibrosis is a hallmark of thioacetamide (TAA) intoxications. MicroRNAs (miRs), such as miR-... more Liver fibrosis is a hallmark of thioacetamide (TAA) intoxications. MicroRNAs (miRs), such as miR-155, have been implied in the pathogenesis of liver disease, and regulated by the antioxidant and anti-inflammatory compound resveratrol (RES). The link between reactive oxygen species (ROS), tumour suppressor p53 (p53), and liver fibrosis-during the pathogenesis of TAA-induced liver injury-associated with miR-155 dysregulation with and without RES incorporation has not been previously studied. Therefore, one group of rats received TAA injections of 200 mg/kg; twice a week at the beginning of week 3 for 8 weeks (TAA group; or model group), whereas the protective group was pretreated daily with RES suspension (20 mg/kg; orally) for the first two weeks and subsequently sustained on receiving both RES and TAA until being sacrificed at the 10th week. Liver injuries developed in the model group were confirmed by a significant (p < 0.0001) elevation of hepatic tissue levels of miR-155, ROS,...

Biomedicines

Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The lin... more Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A signific...

Archives of Physiology and Biochemistry, 2021

BACKGROUND The link between oxidative stress (ROS), apoptosis (p53) and fibrosis (collagen) in ty... more BACKGROUND The link between oxidative stress (ROS), apoptosis (p53) and fibrosis (collagen) in type 2 diabetes mellitus (T2DM)-induced cardiac injury in the presence and absence of the antidiabetic drug, metformin has not been investigated before. MATERIAL AND METHODS T2DM was induced in rats by a combination of high carbohydrate and fat diets (HCFD) and streptozotocin (50 mg/kg) injection. The protection group started metformin (200 mg/kg) treatment 14 days prior to the induction of diabetes and continued on metformin and HCFD until being sacrificed at week 12. RESULTS Diabetes significantly induced blood levels of ROS and left ventricular p53 and collagen expression that was inhibited by metformin. Metformin also significantly reduced glycated haemoglobin and dyslipidemia induced by diabetes. In addition, a significant correlation between ROS-p53-collagen axis and glycaemia and hyperlipidaemia was observed. CONCLUSIONS These findings show that metformin provides substantial protection against diabetic cardiomyopathy-induced ROS-p53 mediated fibrosis and dyslipidemia.

Mini-Reviews in Medicinal Chemistry, 2015

Neuroscience & Biobehavioral Reviews, 2015

Neurons are postmitotic cells that are in permanent cell cycle arrest. However, components of the... more Neurons are postmitotic cells that are in permanent cell cycle arrest. However, components of the cell cycle machinery that are expressed in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) neurons are showing features of a cycling cell and those attributed to a postmitotic cell as well. Furthermore, the unique physiological operations taking place in neurons, ascribed to &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;core cell cycle regulators&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; are also key regulators in cell division. Functions of these cell cycle regulators include neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. In this review, we focus on cohesion and cohesion related proteins in reference to their neuronal functions and how impaired centromere/cohesion dynamics may connect cell cycle dysfunction to aneuploidy in AD.

Angiology, 2011

The role of inflammation is well established in the pathogenesis of atherosclerosis and an increa... more The role of inflammation is well established in the pathogenesis of atherosclerosis and an increased level of circulating inflammatory markers may predict the future risk of atherosclerosis progression and plaque rupture. C-reactive protein (CRP) identification by hypersensitive methods (high-sensitivity CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid endarterectomy (CEA) is a well-established procedure for carotid stenosis treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis reduction may be prevented by the anti-inflammatory effect of statins. This review considers the recent findings on the presence of hsCRP and C3 complement concentration and inflammatory plaque composition as well as their effects on ICA restenosis rate, following eversion CEA with emphasis on human studies.

Archives of Physiology and Biochemistry, 2019

Insulin protects against type 1 diabetes mellitus-induced aortopathy associated with the inhibiti... more Insulin protects against type 1 diabetes mellitus-induced aortopathy associated with the inhibition of biomarkers of vascular injury in rats', Archives of Physiology and Biochemistry.

Archives of Physiology and Biochemistry, 2019

Background: The potential inhibitory effects of captopril, the angiotensin-converting enzyme inhi... more Background: The potential inhibitory effects of captopril, the angiotensin-converting enzyme inhibitor, on thioacetamide (TAA)-induced hepatic mammalian target of rapamycin (mTOR), liver injury enzymes, blood pressure, and biomarkers of inflammation and oxidative stress have not been investigated before. Materials and methods: Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (model group) or were pretreated with captopril (150 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment (protective group). Results: Captopril significantly (p < .05) inhibited TAA-induced hypertension, liver tissue levels of mTOR, TIMP-1, TNF-a, IL-6, MDA; and blood levels of lipids, ALT, and AST. We further demonstrated a significant (p < .01) positive correlation between mTOR scoring and the levels of inflammatory, oxidative and liver injury biomarkers. Conclusions: Captopril protects against TAA-induced mTOR, liver injury enzymes, dyslipidemia, hypertension, inflammation, and oxidative stress.

International Journal of Morphology

Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead t... more Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis-mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

Archives of Physiology and Biochemistry, 2020

Background: We investigated whether the anti-inflammatory and antioxidant agent, resveratrol can ... more Background: We investigated whether the anti-inflammatory and antioxidant agent, resveratrol can inhibit type 2 diabetes mellitus (T2DM)-induced osteoarthritis (OA) in rats and whether it is associated with the suppression of glycaemia, dyslipidemia and inflammatory and oxidative stress biomarkers. Materials and methods: T2DM was induced by streptozotocin (50 mg/kg body weight) and high carbohydrate and fat diet (HCFD). The protective group was put on resveratrol (30 mg/kg) 14 days prior to the induction of diabetes and continued on resveratrol and HCFD until being sacrificed at week 12. Results: Diabetic rats showed a substantial damage to the knee joints and loss of proteoglycans from the articular cartilage, which were effectively but not completly protected by resveratrol. Resveratrol also significantly (p .0029) reduced diabetic up-regulation of HbA1c, hyperlipidaemia, inflammation and oxidative stress. Conclusions: Resveratrol protects against T2DM-induced OA associated with the inhibition of glycated haemoglobin, dyslipidemia, and biomarkers of oxidative stress and inflammation.

Naunyn-Schmiedeberg's Archives of Pharmacology

Ultrastructural Pathology, 2021

ABSTRACT Diabetes-induced osteoarthritis (OA) is a chronic inflammatory disease that damages the ... more ABSTRACT Diabetes-induced osteoarthritis (OA) is a chronic inflammatory disease that damages the cartilage in the joints and could lead to disability. The protective effect of the antioxidant and anti-inflammatory agent, resveratrol, against alterations to the knee articular cartilage ultrastructure induced by type 2 diabetes mellitus (T2DM) associated with the inhibition of dyslipidemia, oxidative stress, and inflammation has not been investigated before. Therefore, we modeled OA in rats 10 weeks post diabetic induction using a high carbohydrate and fat diet and a single injection of streptozotocin (50 mg/kg body weight), and the protective group of rats started resveratrol (30 mg/kg; orally) treatment 2 weeks before diabetic induction and continued on resveratrol until the end of the experiment at week 12. Blood chemistry analysis confirmed hyperglycemia (elevated glucose and glycated hemoglobin, HbA1c), dyslipidemia (elevated triglyceride, cholesterol, and low-density lipoprotein-cholesterol), and upregulation of oxidative stress (malondialdehyde) and inflammatory (C-reactive protein and tumor necrosis factor-α) biomarkers in the model group. In addition, using light and electron microscopy examinations, we also observed in the model group substantial damage to the articular cartilage and profound chondrocyte and territorial matrix ultrastructural alterations such as chondrocytes with degenerated nucleus and mitochondria, scarce cytoplasmic processes, and absence of the fine fibrillar appearance of territorial matrix. Resveratrol pretreatment significantly (p ≤ 0.0029) but not completely protected from T2DM-induced OA. We conclude that resveratrol protects against alterations to the articular cartilage ultrastructure induced secondary to T2DM in rats, which is associated with the inhibition of glycemia, hyperlipidemia, and biomarkers of oxidative stress and inflammation.

Current Pharmacology Reports, 2017

Purpose of Review Numerous studies have shown a positive correlation between serum Hcy level and ... more Purpose of Review Numerous studies have shown a positive correlation between serum Hcy level and various pathological conditions such as coronary, carotid, and peripheral vascular disease. Increased plasma Hcy levels are associated not only with an increased risk of arteriosclerosis but also with atherosclerosis and thrombosis. The aim of this review is to review biochemical mechanisms responsible for development and progression of cardiovascular diseases (CVD). Recent Findings A recent finding shows that cardiac tissue function improves in hyperhomocysteinemic (HHcy) patients after consumption of folic acid and cobalamin. Furthermore, in patients with HHcy plasma levels of nitric oxide (NO) and tetrahydrobiopterin were remarkably decreased compared with the normal individuals. Cardiac endothelial function and coronary flow velocity reserve were significantly disrupted in chronic HHcy patients compared with the control subjects. Summary Lowering elevated level of Hcy by supplementation with folic acid and B12 vitamin reduces plasma level of Hcy and substantially reduces the risk of CVD. The combination of consuming supplements of B12, B6, and folate on a daily basis reduces the progression of atherosclerosis, measured by the area of the carotid artery plaques and their administration, improve CVD and may slightly prevent the incidence of atherosclerotic vascular events. A correlation between Hcy and hypertension indicates that Hcy levels could be used as a potential marker for atherosclerosis progression.

Ultrastructural Pathology, 2019

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chond... more We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 μL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA +STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly (p < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.

Hypertension, 1999

The genes encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2, also known... more The genes encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2, also known as prostaglandin-endoperoxide synthase-2) are induced in many types of cells in response to proinflammatory cytokines. We have previously shown that interleukin-1␤ (IL) stimulates iNOS and COX-2 mRNA in cardiac myocytes. Because IL has been shown to activate mitogen-activated protein kinase (MAPK) signaling pathways in many different cells, we tested whether the p42/44 and p38 MAPK pathways were involved in IL stimulation of iNOS and COX-2, using a specific inhibitor of p42/44 activation, PD98059 (PD), and the p38 inhibitor SB205380 (SB). Nitrites were measured using the Griess reagent, prostaglandin PGE 2 by an enzyme immunoassay, iNOS and COX-2 protein by Western blot analysis, and iNOS mRNA by Northern blot analysis. Tested separately, the p38 kinase and MAPK inhibitors partially reduced IL stimulation of nitrite, iNOS protein, and iNOS mRNA; used together, they completely abolished the effect of IL. SB and PD inhibited IL-stimulated COX-2 protein by 60% and 80%, respectively, and IL-stimulated COX-2 protein was totally prevented by the combination of inhibitors. PGE 2 production was inhibited more than 99% by either drug alone, suggesting a posttranslational effect on enzyme activity. To test whether this posttranslational effect involved the cytosolic phospholipase A 2 (cPLA 2) isoform, Western blots were probed for cPLA 2 protein. Results indicated that IL stimulated cPLA 2 activity and synthesis, which was inhibited by SB but not PD. These data indicate that (1) IL induction of iNOS synthesis depends on both the p42/44 and p38 signaling pathways, acting primarily at the level of transcriptional regulation; and (2) IL regulation of COX-2 synthesis involves the p42/44 and p38 signaling pathways, with an additional level of regulation occurring posttranslationally, perhaps at the level of activation of the cPLA 2 isoform, which may be involved in intracellular signaling, as well as regulation of arachidonic acid release for COX-2 activity. (Hypertension. 1999;33[part II]:276-282.

Collection of Czechoslovak Chemical Communications, 2006

Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with ... more Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with almost a total loss of estrogenic activity, we studied the effects of some of these compounds on estrogen receptors (ER), the translocation of the estrogen-ER complexes formed in presence of competing substances into the nucleus, as well as the binding of these complexes to DNA. The results of uterotrophic effects of analysed derivatives are in agreement with the influence of these compounds on activity and binding parameters of estrogen receptors. Namely, compounds that show relatively high antiestrogenic activity predominantly increaseKdand inhibit translocation to nuclei of radioactive complexes formed in their presence. On the other hand, compounds that do not significantly change binding parameters of estrogen receptors do not show antiestrogenic effect inin vivoexperiments.

International Journal of Morphology, 2017

Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver f... more Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver failure are among the common public health problems. We sought to investigate the damage to the hepatocyte ultrastructure induced by high fat diets (HFD) and compared the therapeutic effects at the cellular level of two antioxidant and lipid lowering agents; Crataegus aronia extracts and simvastatin on hepatic steatosis. Rats were either fed with HFD (model group) or low fat diets (LFD) (control group) for 15 weeks before being sacrificed and therapeutic groups started the treatment with these agents after week 11 until the sacrifice day. Harvested liver tissues were examined using transmission electron microscopy (TEM) and liver homogenates were assayed for markers of antioxidative stress that are known to be modulated in liver injury. TEM examinations of the model group showed a profound damage to the hepatocytes compared to the control group as demonstrated by steatosis, damaged mitochondria and vaculated cytoplasm, disrupted rough and smooth endoplasmic reticulum and nuclear membrane, dilated intercellular space between hepatocytes, and alterations in lysosomes. In addition, HFD ameliorated the anti-oxidant glutathione (GSH) and augmented the oxidative stress TBARS biomarkers. Both Crataegus aronia and simvastatin significantly reduced lipids and TBARS, and treated damage to hepatic cells, but hepatocyte structures were differentially responded to these agents. However, only Crataegus aronia induced GSH (p=0.001). We conclude that HFD-induced hepatic steatosis caused a substantial damage to the hepatocyte's ultrastructures, and Crataegus aronia and simvastatin treatments differentially reversed hepatic injuries.

International Journal of Morphology, 2018

Metformin pretreatment ameliorates diabetic nephropathy induced by a combination of high fat diet... more Metformin pretreatment ameliorates diabetic nephropathy induced by a combination of high fat diet and streptozotocin in rats.

International Journal of Morphology, 2020

The potential inhibitory effect of the insulin mimicking agent, vanadium on type 2 diabetes melli... more The potential inhibitory effect of the insulin mimicking agent, vanadium on type 2 diabetes mellitus (T2DM)induced alterations to the aorta ultrastructure associated with the suppression of dyslipedima and biomarkers of inflammation has not been investigated before. Therefore, we tested whether vanadium can protect against aortic injury induced secondary to T2DM possibly via the inhibition of blood lipid and inflammatory biomarkers. T2DM was induced in rats by a high-fat diet and streptozotocin (50 mg/ kg), and the treatment group started vanadium treatment five days post diabetic induction and continued until being sacrificed at week 10. Using light and electron microscopy examinations, we observed in the model group substantial damage to the aorta tissue such as damaged endothelium, degenerative cellular changes with vacuolated cytoplasm and thickened internal elastic lamina that were substantially ameliorated by vanadium. Administration of vanadium to diabetic rats also significantly (p<0.05) reduced blood levels of glucose, hyperlipidemia and biomarkers of inflammation (TNF-a, IL-6). We conclude that vanadium protects against T2DM-induced aortic ultrastructural damage in rats, which is associated with the inhibition of blood sugar and lipid and inflammatory biomarkers.

International Journal of Morphology, 2020

Menopause complications such as cardiovascular and bone diseases represent a major public health ... more Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.

Diagnostics

Liver fibrosis is a hallmark of thioacetamide (TAA) intoxications. MicroRNAs (miRs), such as miR-... more Liver fibrosis is a hallmark of thioacetamide (TAA) intoxications. MicroRNAs (miRs), such as miR-155, have been implied in the pathogenesis of liver disease, and regulated by the antioxidant and anti-inflammatory compound resveratrol (RES). The link between reactive oxygen species (ROS), tumour suppressor p53 (p53), and liver fibrosis-during the pathogenesis of TAA-induced liver injury-associated with miR-155 dysregulation with and without RES incorporation has not been previously studied. Therefore, one group of rats received TAA injections of 200 mg/kg; twice a week at the beginning of week 3 for 8 weeks (TAA group; or model group), whereas the protective group was pretreated daily with RES suspension (20 mg/kg; orally) for the first two weeks and subsequently sustained on receiving both RES and TAA until being sacrificed at the 10th week. Liver injuries developed in the model group were confirmed by a significant (p < 0.0001) elevation of hepatic tissue levels of miR-155, ROS,...

Biomedicines

Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The lin... more Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A signific...