Amir Ghorbanihaghjo - Academia.edu (original) (raw)

Papers by Amir Ghorbanihaghjo

Cancer Research, 2004

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis fa... more Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of structurally related cytokines. TWEAK acts on responsive cells via binding to a cell surface receptor named Fn14. Recent studies have demonstrated that TWEAK can stimulate numerous cellular responses including cell proliferation, migration, and proinflammatory molecule production. It has also been reported that TWEAK can stimulate blood vessel formation in the rat cornea angiogenesis assay, but it is presently unknown whether this cytokine could play a role in the pathological angiogenesis associated with human diseases such as cancer, rheumatoid arthritis, and diabetic retinopathy. In the present study we investigated whether TWEAK was expressed in human tumors and whether it could promote tumor growth and angiogenesis in vivo. TWEAK mRNA expression was detected in many tumor types by cDNA array hybridization analysis, and TWEAK protein expression was confirmed in hu...

Objective(s): Hypercholesterolemia is a common metabolic disorder in developing and developed cou... more Objective(s): Hypercholesterolemia is a common metabolic disorder in developing and developed countries and is associated with the increased rates of chronic kidney disease (CKD). Statin therapy could reduce cholesterol synthesis as well as progression of CKD. Diversity between statins causes variety in pharmacokinetics and pharmacodynamics and also their pleiotropic effects. In the present investigation we aimed to evaluate the protective potentials of both atorvastatin (Ator) (as lipid-soluble statin) and rosuvastatin (Ros) (as water-soluble statin) against renal histopathological damages in the high cholesterol diet induced hypercholesterolemic rats (HCDIHR). Materials and Methods: Serum lipid profile, oxidized low density lipoprotein (OX-LDL), malondialdehyde (MDA), urea and creatinine levels, as well as renal histopathology were evaluated. Results: While Ros acted better than Ator to reduce serum low density lipoprotein cholesterol (LDL-C) (P<0.01), atherogenic index (AI) (P...

European Journal of Pharmacology, 2019

Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic n... more Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

International journal of rheumatic diseases, 2018

This study aimed to follow up patients with polymyositis (PM) and/or dermatomyositis (DM) to dete... more This study aimed to follow up patients with polymyositis (PM) and/or dermatomyositis (DM) to determine survival rate, pattern of disease, response to treatment, malignancy incidence and poor prognostic factors (PPFs). A total of 76 patients with PM (n = 47) and/or DM (n = 29) based on Bohan and Peter diagnostic criteria referred to the Imam-Reza Hospital were followed up from 2004 to 2016. The follow-up period was considered from diagnosis to patient's death or last visit. All patients underwent physical examinations and data including age, sex, disease duration, disease subtype, pattern of disease, PPFs and malignancy incidence were collected. Mean age at diagnosis was 45.49 ± 10.88 years and women were predominant (84.2%). Course of disease in the majority of patients (52.6%) was polyphasic, followed by monophasic (31.6%) and chronic-progressive (5.3%). The 1-, 5- and 10-year survival rates were 96%, 93% and 92%, respectively. Delay in treatment and dysphagia were common PPFs ...

Journal of physiology and biochemistry, Jan 14, 2018

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progres... more Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin express...

Chemico-biological interactions, 2017

Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic pa... more Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients. Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or pleotropic effects. Depending on their penetrance into the extra-hepatic cells, statins have different effects on mevalonate/isoprenoid pathway. Lipophilic statins diffuse into all cells and hydrophilic ones use a variety of membrane transporters to gain access to cells other than hepatocytes. It has been suggested that the lower accessibility of statins for extra-hepatic tissues may result in the compensatory induction of mevalonate/isoprenoid pathway and so cancer developi...

Journal of cardiovascular and thoracic research, 2017

Hydroxy-Methyl-Glutaryl-CoA reductase (HMGCR) - the main enzyme of the cholesterol biosynthesis p... more Hydroxy-Methyl-Glutaryl-CoA reductase (HMGCR) - the main enzyme of the cholesterol biosynthesis pathway - is mostly inhibited by statins in hepatocytes. In spite of the other tissues, liver utilizes cholesterol in different ways such as the synthesis of bile acids, excretion in to the intestine and synthesis of lipoproteins. Therefore, statins theoretically alter these pathways; although, there have not been such effects. In this review, we aim to show the roles of extra-hepatic tissues, in particular intestine, adipose and cutaneous tissues in providing the cholesterol after reduction of the whole body cholesterol content by statins.

Sao Paulo Medical Journal, 2016

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanid... more ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of T...

Saudi Medical Journal, Nov 1, 2007

The purpose of the study was to determine whether DNA polymorphisms at the renin-angiotensinaldos... more The purpose of the study was to determine whether DNA polymorphisms at the renin-angiotensinaldosterone (RAS) genes were associated with evolution to renal scar formation and, consequently, with reflux nephropathy (RN) in patients with vesicoureteral reflux (VUR). Some authors have suggested that the DD genotype of the angiotensin-converting enzyme (ACE) gene would be an adverse renal prognosis factor. We recruited 246 patients (aged 3 months to 22 years) from four Spanish hospitals. These included 69 patients with VUR, 110 with RN (determined by absence/presence of renal scarring on dimercaptosuccinc acid scan), 27 with chronic renal failure due to RN, and 40 patients (control group) with urinary tract infection and normal findings on renal ultrasonography and voiding cystoureterogram. The ACE I/D, angiotensin II type 1 receptor AT1 A1166C, angiotensin II type 2 receptor A3123C AT2, and angiotensinogen AGT M235T polymorphisms were determined on the basis of polymerase chain reaction amplification. ACE serum levels were determined by spectrophotometric methods. We found no statistical differences in the distribution of RAS polymorphisms between the different groups. The ACE D allele was linked to higher ACE serum levels. We found no association between ACE I/D polymorphism and presence of hypertension, proteinuria, grade of VUR, or unilateral/bilateral VUR. Patients with the DD genotype had a lower incidence of febrile urinary tract infection as a first symptom of VUR/RN (P<0.05). We conclude that genetic polymorphisms of RAS components are not independent prognostic indicators of renal scarring in patients with VUR.

Iranian journal of kidney diseases, 2015

Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla protein (MGP) are crucial mediators... more Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla protein (MGP) are crucial mediators of vascular calcification and are involved in the development of vascular complications in chronic kidney diseases. This study was set out to investigate the relationship between plasma GAS6 levels and MGP in patients with end-stage renal disease on maintenance hemodialysis. Forty-six hemodialysis and 46 healthy individuals with normal kidneys were recruited. Plasma GAS6 and MGP concentrations and related biochemical factors were quantified as well as collection of data on clinical characteristics. Plasma GAS6 levels were significantly higher in the hemodialysis patients as compared with the control group (763.52 ± 187.91 pg/mL versus 421.63 ± 189.91 pg/mL, P < .001). Plasma MGP concentration was significantly lower in the hemodialysis patients than the control group (52.35 ± 12.35 ng/mL versus 6.60 ± 19.54 ng/mL, P < .001). The levels of GAS6 were inversely associated with MGP (r...

Iranian Red Crescent Medical Journal, 2014

Background: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral metabolism; espe... more Background: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral metabolism; especially vascular calcification in uremic patients. Objectives: The aim of the present study was to evaluate of ET-1, high-sensitivity C-reactive protein (hs-CRP) and mineral metabolites as the main factors for vascular calcification and inflammation in hemodialysis (HD) patients. Patients and Methods: In this cross-sectional study, 46 chronic stable HD patients were selected from nephrology departments of Tabriz University of Medical Sciences affiliated hospitals and classified based on phosphorus (P), CaP product (Ca × P) and intact Parathyroid Hormone (iPTH) levels. We evaluated fasting serum ET-1and hs-CRP levels by the standard methods and compared with 46 healthy control subjects. Results: The levels of serum hs-CRP and ET-1 were significantly higher in the patient's group compared with controls (4.40 ± 1.26 vs. 1.38 ± 1.61, P < 0.0001, and 2.31 ± 0.87 vs. 0.75 ± 0.48, P < 0.0001, respectively) and with regard to Ca × P product cutoff point (3.99 ± 0.78 vs.

Journal of Renal Nutrition, 2009

We examined the effects of zinc supplementation on serum zinc and C-reactive protein concentratio... more We examined the effects of zinc supplementation on serum zinc and C-reactive protein concentrations in hemodialysis patients. This was a randomized, double-blinded, placebo-controlled clinical trial. This study was conducted at the Shahid Faghihi and Namazi Dialysis Centers in Shiraz, Iran. Fifty-five hemodialysis patients (32 men and 23 women) participated after meeting the following criteria: zinc deficiency, treated for a minimum of 6 months; no record of hospitalizations in the preceding 3 months; and hemodialysis treatment 2 to 3 times per week. Patients were randomly divided into two groups. The zinc supplementation group (n=28) received a 220-mg zinc sulfate capsule, and the control group (n=27) received a placebo capsule (220 mg corn starch), for 42 days. Fasting, predialysis serum samples were collected on days 0 and 42 to determine serum zinc and C-reactive protein levels. After supplementation, subjects in the zinc-supplemented group showed significant increases in serum zinc concentrations, from 57.4+/-2.4 microg/dL SEM on day 0 to 88.4+/-4.8 microg/dL SEM on day 42. Serum C-reactive protein concentrations were initially high among subjects in the control (15.1+/-3.9 mg/L SEM) and zinc-supplemented (13.5+/-3.8 mg/L SEM) groups. Serum C-reactive protein concentrations in the control group increased throughout the study period, but did not reach statistical significance. A progressive decrease in serum C-reactive protein concentrations was observed in the zinc-supplemented group from the beginning (13.5+/-3.8mg/L SEM) to the end (10.5+/-3.5mg/L SEM) of the study, but this event was not significant. Zinc supplementation intake may cause an increase in serum zinc concentrations, leading to a decrease of inflammation in hemodialysis patients.

Indian Journal of Ophthalmology, 2009

To evaluate the eff ects of onion juice on sodium-selenite induced cataract formation. Materials ... more To evaluate the eff ects of onion juice on sodium-selenite induced cataract formation. Materials and Methods: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only diff erence being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: Both eyes of all rats in Group 1 did not exhibit cataract formation. In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The diff erence in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were signiÞ cant (P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were signiÞ cantly lower than the values in lenses of all rats in Group 1 (P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 (P = 0.001, 0.020, 0.001). Conclusion: Instillation of onion juice into the rat eyes can eff ectively prevent selenite-induced cataract formation. This eff ect was associated with increased TA level, SOD and GPX activities in the lens.

Clinical Biochemistry, 2012

The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factor... more The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients. Serum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods. In the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09-20.36) ng/mL vs. 1.65(0.24-7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75-81.48) ng/mL vs. 38.76(22.26-89.07) ng/mL, p=0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1-8.50) mg/L vs. 1.1(0.1-7.9) mg/L, p=0.003]. Although our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.

Clinical Biochemistry, 2005

Objectives: This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-... more Objectives: This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-C, apolipoproteins and paraoxonase (PON) activity in stable hemodialysis patients. Design and methods: 64 hemodialysis patients were treated with ND at a dose of 100 mg/I.M./week for 4 months. HDL-C, Apo-AI, Apo B, concentrations and PON activity were measured before and after 2 and 4 months of treatment as well as 2 months after withdrawing the treatment. Results: After 4 months of treatment, an elevation in the serum levels of Apo B (P < 0.0001) and a marked decrease in the concentration of HDL-C (P < 0.0001), Apo-AI (P < 0.0001) and PON activity (P < 0.0001) were found. A significant correlation between PON and both Apo-AI (r = 0.270, P < 0.04) and HDL-C (r = 0.455, P < 0.0001) and also between HDL-C and Apo-AI (r = 0.305, P < 0.02) were found. Conclusion: Results revealed the adverse effects of ND on apolipoprotein levels in our study population. It is possible that ND reduces PON activity mostly by reducing both the HDL-C and Apo-AI levels.

Lipids in health and disease, Jan 22, 2004

Atherosclerosis is the main cause of mortality and morbidity in end stage renal diseases (ESRD), ... more Atherosclerosis is the main cause of mortality and morbidity in end stage renal diseases (ESRD), especially in hemodialysis (HD) patients. In addition the classic risk factors for atherosclerosis, non classical risk factors, such as high lipid peroxidation and low antioxidants, also, are culprit in the pathogenesis. We tested lipid peroxidation and total antioxidant levels in forty five stable hyperlipidemic HD males (age range 40-60 years) before, after 45 and 90 days of prescription of 20 mg/day Lovastatin for three months. Malondialdehyde (MDA), as prototype of lipid peroxidation, and total antioxidants (TA) were measured by flourimetric and spectrophotometric assays, respectively. Serum triglyceride (Tg) (213.7 +/- 112.4 mg/dl vs. 153.4 +/- 54.8 mg/dl p = 0.003), serum cholesterol (C) (185.8 +/- 48.3 mg/dl vs. 149.3 +/- 37.8 mg/dl, p = 0.014), LDL-C (120.1 mg/dl +/- 48.9 vs. 84.8 +/- 43.7 mg/d, p = 0.001), VLDL-C (40.7 +/- 18.9 mg/dl vs. 30.7 +/- 10.9 mg/dl, p = 0.025), MDA (13....

Clinical and …, 2008

In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated i... more In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms. After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E-L-). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively. 8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P &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;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;lt; 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P &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;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;lt; 0.001; r = 0.35, P = 0.006). The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.