yusuf ali | Southeast University (Bangladesh) (original) (raw)
Papers by yusuf ali
Journal of Scientific Research, 2013
The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (ab... more The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (abbreviated as NSSE) on adrenaline-induced dyslipidemia and left ventricular hypertrophy (LVH) in rats. Intraperitoneal injection of adrenaline for two weeks induced dyslipidemia whereas injection of adrenaline for four weeks induced both dyslipidemia and LVH significantly, compared with normal rats. Injection of NSSE with different doses (0.5, 1 and 1.5 mg/kg body weight, BW) on adrenaline-induced dyslipidemic rats (AIDRs) for two weeks significantly reduced TC, TG and LDL-C and increased HDL-C compared with AIDRs and the most effective dose was 1.5 mg/kg BW. Treatment with NSSE (1.5 mg/kg BW) on AIDRs for eight weeks, significant anti-dyslipidemic effect was observed. Moreover, NSSE significantly increased free radical scavenging activity and attenuated the LVH and cardiomyocyte size compared with AIDRs. The results suggested that the anti-dyslipidemic, antioxidative and inhibitory effec...
British Journal of Pharmacology, 2019
might have direct effects on adrenal aldosterone production via V2R antagonism. Therefore, we inv... more might have direct effects on adrenal aldosterone production via V2R antagonism. Therefore, we investigated the potential of Tolv in the regulation of adrenal aldosterone synthesis and studied the molecular mechanisms using aldosterone-producing H295R human adrenocarcinoma cells and AngII-induced hyper-aldosterone rat model. Methods In vitro studies Cell culture The human adrenocortical carcinoma cell line NCI-H295R (Cat# CRL-2128, RRID:CVCL_0458) (Rainey et al., 1994) was obtained from the ATCC (American Type Culture Collection, Manassas, VA), and cultured in DMEM/F12 (1:1) medium supplemented with 2.5% Nu-serum, 1% ITS+ premix supplement (insulin, 6.25 mg/ml; transferrin, 6.25 mg/ml; selenium, 6.25 ng/ml; and linoleic acid, 5.35 mg/ml), and antibiotics (penicillin and streptomycin). The cells were maintained at 37 °C in a humidified atmosphere containing air and carbon dioxide (95%/5%, vol/vol). The H295R cell lines provide a good in vitro system for the analysis of the human adrenal steroidogenic pathway at the level of hormone production and gene expression (Oskarsson et al., 2006).
International Journal of Molecular Sciences, 2019
Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypert... more Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.
Circulation, 2018
Introduction: Tolvaptan (Tolv), a selective vasopressin type 2 receptor (V2R) antagonist, therapy... more Introduction: Tolvaptan (Tolv), a selective vasopressin type 2 receptor (V2R) antagonist, therapy avoids stimulation of aldosterone production despite its strong diuretic effect. However, its influ...
Pharmacology & Pharmacy, 2014
Worldwide prevalence of diabetes mellitus has become an issue of great concern in current decades... more Worldwide prevalence of diabetes mellitus has become an issue of great concern in current decades. This life threatening disease is associated with worsening of glycemic control and progressive metabolic dysfunctions. Objective: Current study aimed to investigate the effect of hydroxychloroquine (HCQ) as an adjunct to glibenclamide or metformin on glycemic control in alloxan induced diabetic rats. Methods: HCQ was combined separately with two conventional anti-diabetic drugs; glibenclamide and metformin. At first, alloxan (120 mg/kg) induced diabetic rats were treated with single dose of metformin (850 mg/70 kg BW), glibenclamide (10 mg/70 kg BW) and HCQ (300 mg/70 kg BW) intraperitoneally once daily for two weeks. Then non fixed dose combinations of glibenclamide (5 mg/70 kg BW) with HCQ (150 mg/70 kg BW) and metformin (425 mg/70 kg BW) with HCQ (150 mg/70 kg BW) were injected along with those of the three drugs alone once daily for four weeks. Results: In alloxan induced diabetic rats, glibenclamide, metformin and their combination therapies reduced blood glucose level significantly but combination therapies are the most effective. Glibenclamide or metformin in combination with HCQ also significantly (P < 0.05) reduced the elevated levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol (LDL-C) level and increased high density lipoprotein cholesterol (HDL-C) level. Moreover, HCQ potentiates the liver glycogen synthesis of metformin or glibenclamide. Conclusion: Outcomes of this investigation indicate that combination of glibenclamide or metformin with HCQ improves glycemic control and provides additional metabolic benefits, not achieved
Journal of Scientific Research, 2012
The present study was designed to investigate the effects of combination drugs (metformin and ato... more The present study was designed to investigate the effects of combination drugs (metformin and atorvastatin) on long-term alloxan-induced diabetes with CVD in rats. In short-term alloxan-induced diabetic rats, metformin reduced significant amount of glucose in blood, but it had no significant effect on lipid profile. Atorvastatin significantly reduced TC, TG and LDL-C, whereas it increased significant amount of HDL-C. However, pathological changes of heart were not observed after short-term induction of alloxan in rats. In long-term induction of diabetes by alloxan, LV hypertrophy was observed and cardimyocyte size in rats was increased. Atorvastatin alone and in combination with metformin significantly reduced the LV hypertrophy, cardiomyocyte size, TC, TG and LDL-C level. They increased significant amount of HDL-C level and showed significant DPPH free radical scavenging activity. Present findings may suggest that treatment with combination therapy is more effective than mono-thera...
European Heart Journal
Background: Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovas... more Background: Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases including heart failure and cardiac hypertrophy. It is known that BNP levels are relatively higher in patients with chronic kidney disease with no heart disease; however, its mechanism remains unclear. Purpose: Our purpose is to determine whether a substance in the renal papillary tip is associated with BNP or not. Methods: We developed a BNP reporter mouse, pBNP-tdTomato transgenic (Tg) mice, with the DNA fragments of mouse BNP 1.1k promoter into the expression vector of tdTomato and six lines of Tg mice were screened. To evaluate the activation of BNP promotor in aged mice, we examined the expression of tdTomato in each of organs from pBNP-tdTomato Tg mice. We attempted to establish a primary culture of the pBNP-tdTomato-positive cells from kidneys of BNP reporter mice. We investigated the effects of an extract of the papillary tip of rat on the expression of BNP in cultured rat neonatal cardiomyocytes with the use of northern blot and ELISA measurement. The blood pressure, serum BNP and urine cGMP were measured in stroke-prone spontaneous hypertensive rats (SHR-SP) after the extract from the papillary tip was injected intraperitoneally. Ligation of the rats' left anterior descending coronary artery was performed, and the effects of extracts from the papillary tips of kidneys of heart failure rats were examined five days after the induction of myocardial infarction. Results: In addition to the expression of tdTomato in cardiomyocytes, we occasionally found that the BNP promoter was activated specifically in the papillary tip of the kidneys and was not accompanied by BNP mRNA expression. pBNP-tdTomato-positive cells appeared to be interstitial and were not observed in any area of the kidneys except for the papillary tip. No evidence was observed to show the existence of BNP isoform or other nucleotide expression than BNP from around the BNP promotor region. Unexpectedly, both the expression and the secretion of BNP increased in the primary cultured neonatal cardiomyocytes after the treatment with the extract of the renal papillary tip. We were able to culture papillary tip tissue containing tdTomato-positive cells for more than 2 months, but no proliferation was observed. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure accompanied by increasing serum BNP and urinary cGMP production in SHR-SP. Furthermore, the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes. Conclusions: These results suggest the interstitial cells in the renal papillary tip possess a substance that can stimulate BNP production and secretion from cardiomyocytes in vivo and in vitro.
Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypert... more Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.
Background and Purpose: We investigated the inhibitory effect and associated molecular mechanisms... more Background and Purpose: We investigated the inhibitory effect and associated molecular mechanisms of tolvaptan on angiotensin II (AngII)-induced aldosterone production in vitro and in vivo.
Aims GJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions.... more Aims GJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions. This study investigated whether GJB4 plays an important role in human heart disease and function.
The present study was designed to investigate the effects of combination drugs (metformin and ato... more The present study was designed to investigate the effects of combination drugs (metformin and atorvastatin) on long-term alloxan-induced diabetes with CVD in rats. In short-term alloxan-induced diabetic rats, metformin reduced significant amount of glucose in blood, but it had no significant effect on lipid profile. Atorvastatin significantly reduced TC, TG and LDL-C, whereas it increased significant amount of HDL-C. However, pathological changes of heart were not observed after short-term induction of alloxan in rats. In longterm induction of diabetes by alloxan, LV hypertrophy was observed and cardimyocyte size in rats was increased. Atorvastatin alone and in combination with metformin significantly reduced the LV hypertrophy, cardiomyocyte size, TC, TG and LDL-C level. They increased significant amount of HDL-C level and showed significant DPPH free radical scavenging activity. Present findings may suggest that treatment with combination therapy is more effective than mono-therapy for preventing diabetes with CVD in rats.
The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (ab... more The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (abbreviated as NSSE) on adrenaline-induced dyslipidemia and left ventricular hypertrophy (LVH) in rats. Intraperitoneal injection of adrenaline for two weeks induced dyslipidemia whereas injection of adrenaline for four weeks induced both dyslipidemia and LVH significantly, compared with normal rats. Injection of NSSE with different doses (0.5, 1 and 1.5 mg/kg body weight, BW) on adrenaline-induced dyslipidemic rats (AIDRs) for two weeks significantly reduced TC, TG and LDL-C and increased HDL-C compared with AIDRs and the most effective dose was 1.5 mg/kg BW. Treatment with NSSE (1.5 mg/kg BW) on AIDRs for eight weeks, significant anti-dyslipidemic effect was observed. Moreover, NSSE significantly increased free radical scavenging activity and attenuated the LVH and cardiomyocyte size compared with AIDRs. The results suggested that the antidyslipidemic, antioxidative and inhibitory effects of NSSE on LVH were closely resembled to that of atorvastatin, a most effective lipid lowering agent. Therefore, NSSE might be used as a therapeutic alternative or as a combination with drug in the treatment of dyslipidemia and LVH.
Background Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovasc... more Background Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.
Bangladesh Pharmaceutical Journal, 2015
ABSTRACT Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated th... more ABSTRACT Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated the hypothesis that the antidiabetic drugs glibenclamide and metformin, in combination with hydroxychloroquine (HCQ) offer additional protection for the pancreas against oxidative stress and produce hepatoprotective effect in alloxan-induced diabetic rats. Diabetes was induced in male Long-Evans rats by a single dose of alloxan (120 mg/kg; i.p.). Different groups of diabetic animals were treated with glibenclamide (10 mg/70 kg, i.p.), metformin (850 mg/70 kg, i.p.), HCQ (300 mg/70 kg, i.p.) and combination of both glibenclamide and metformin with HCQ, separately for a period of 28 days. Diabetic rats had significantly elevated levels of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), while catalase (CAT) and superoxide dismutase (SOD) activity were significantly reduced. Glibenclamide and metformin produced no significant effects on antioxidant enzymes but both showed significant (p<0.05) result in reducing SGOT and SGPT level in diabetic rats. In contrast, the combination of glibenclamide or metformin with HCQ showed better effect on up-regulation of CAT and SOD activity and down-regulation of SGOT and SGPT activity in comparison with the antidiabetic drug alone. These findings suggest that, HCQ potentiates the effect of glibenclamide and metformin to protect pancreas against oxidative stress and produce hepatoprotective effect in diabetic rats.
Pharmacology & Pharmacy, 2014
The aim of the current study is to investigate the effect of combination of glibenclamide; an ant... more The aim of the current study is to investigate the effect of combination of glibenclamide; an antidiabetic drug and simvastatin; a HMG-CoA reductase inhibitor on long-term (four weeks) alloxaninduced diabetes rats (ADRs). Methods: Alloxan (120 mg/kg body weight, BW) was injected intraperitonially (i.p.) in rats. At first alloxan (120 mg/kg BW) induced diabetic rats were treated with single dose of glibenclamide (1.2 mg/70kg BW) and simvastatin (10 mg/70kg BW) for two weeks. Then fixed dose combinations of glibenclamide (0.6 mg/70kg BW) and simvastatin (5 mg/70kg BW) were injected along with those of two drugs for four weeks. Results: At first it was found that glibenclamide reduced significant amount of glucose in blood, but it had no significant effect on lipid profile on short term (two weeks) ADRs. In contrast, simvastatin had no effect on blood glucose level, whereas it significantly reduced total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and increased significant amount of high density lipoprotein cholesterol (HDL-C). However, pathological changes of pancreas's Islets of Langerhans were observed only after long-term (four weeks) induction of alloxan in rats. The inhibitory effect of combination therapy on blood glucose, TC, TG and LDL-C level was higher than those of monotherapy alone on long term ADRs. In addition, treatment with combination therapy on long term ADRs showed higher amount of HDL-C level and super oxide dismutase and catalase enzyme activity than those with monotherapy. They also decreased serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) level. Administration of simvastatin recovered Langerhans cells from shrinkage whereas glibenclamide displayed slight recovery. But the * Corresponding author.
The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (ab... more The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (abbreviated as NSSE) on adrenaline-induced dyslipidemia and left ventricular hypertrophy (LVH) in rats. Intraperitoneal injection of adrenaline for two weeks induced dyslipidemia whereas injection of adrenaline for four weeks induced both dyslipidemia and LVH significantly, compared with normal rats. Injection of NSSE with different doses (0.5, 1 and 1.5 mg/kg body weight, BW) on adrenaline-induced dyslipidemic rats (AIDRs) for two weeks significantly reduced TC, TG and LDL-C and increased HDL-C compared with AIDRs and the most effective dose was 1.5 mg/kg BW. Treatment with NSSE (1.5 mg/kg BW) on AIDRs for eight weeks, significant anti-dyslipidemic effect was observed. Moreover, NSSE significantly increased free radical scavenging activity and attenuated the LVH and cardiomyocyte size compared with AIDRs. The results suggested that the antidyslipidemic, antioxidative and inhibitory effects of NSSE on LVH were closely resembled to that of atorvastatin, a most effective lipid lowering agent. Therefore, NSSE might be used as a therapeutic alternative or as a combination with drug in the treatment of dyslipidemia and LVH.
Journal of Scientific Research, 2013
The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (ab... more The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (abbreviated as NSSE) on adrenaline-induced dyslipidemia and left ventricular hypertrophy (LVH) in rats. Intraperitoneal injection of adrenaline for two weeks induced dyslipidemia whereas injection of adrenaline for four weeks induced both dyslipidemia and LVH significantly, compared with normal rats. Injection of NSSE with different doses (0.5, 1 and 1.5 mg/kg body weight, BW) on adrenaline-induced dyslipidemic rats (AIDRs) for two weeks significantly reduced TC, TG and LDL-C and increased HDL-C compared with AIDRs and the most effective dose was 1.5 mg/kg BW. Treatment with NSSE (1.5 mg/kg BW) on AIDRs for eight weeks, significant anti-dyslipidemic effect was observed. Moreover, NSSE significantly increased free radical scavenging activity and attenuated the LVH and cardiomyocyte size compared with AIDRs. The results suggested that the anti-dyslipidemic, antioxidative and inhibitory effec...
British Journal of Pharmacology, 2019
might have direct effects on adrenal aldosterone production via V2R antagonism. Therefore, we inv... more might have direct effects on adrenal aldosterone production via V2R antagonism. Therefore, we investigated the potential of Tolv in the regulation of adrenal aldosterone synthesis and studied the molecular mechanisms using aldosterone-producing H295R human adrenocarcinoma cells and AngII-induced hyper-aldosterone rat model. Methods In vitro studies Cell culture The human adrenocortical carcinoma cell line NCI-H295R (Cat# CRL-2128, RRID:CVCL_0458) (Rainey et al., 1994) was obtained from the ATCC (American Type Culture Collection, Manassas, VA), and cultured in DMEM/F12 (1:1) medium supplemented with 2.5% Nu-serum, 1% ITS+ premix supplement (insulin, 6.25 mg/ml; transferrin, 6.25 mg/ml; selenium, 6.25 ng/ml; and linoleic acid, 5.35 mg/ml), and antibiotics (penicillin and streptomycin). The cells were maintained at 37 °C in a humidified atmosphere containing air and carbon dioxide (95%/5%, vol/vol). The H295R cell lines provide a good in vitro system for the analysis of the human adrenal steroidogenic pathway at the level of hormone production and gene expression (Oskarsson et al., 2006).
International Journal of Molecular Sciences, 2019
Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypert... more Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.
Circulation, 2018
Introduction: Tolvaptan (Tolv), a selective vasopressin type 2 receptor (V2R) antagonist, therapy... more Introduction: Tolvaptan (Tolv), a selective vasopressin type 2 receptor (V2R) antagonist, therapy avoids stimulation of aldosterone production despite its strong diuretic effect. However, its influ...
Pharmacology & Pharmacy, 2014
Worldwide prevalence of diabetes mellitus has become an issue of great concern in current decades... more Worldwide prevalence of diabetes mellitus has become an issue of great concern in current decades. This life threatening disease is associated with worsening of glycemic control and progressive metabolic dysfunctions. Objective: Current study aimed to investigate the effect of hydroxychloroquine (HCQ) as an adjunct to glibenclamide or metformin on glycemic control in alloxan induced diabetic rats. Methods: HCQ was combined separately with two conventional anti-diabetic drugs; glibenclamide and metformin. At first, alloxan (120 mg/kg) induced diabetic rats were treated with single dose of metformin (850 mg/70 kg BW), glibenclamide (10 mg/70 kg BW) and HCQ (300 mg/70 kg BW) intraperitoneally once daily for two weeks. Then non fixed dose combinations of glibenclamide (5 mg/70 kg BW) with HCQ (150 mg/70 kg BW) and metformin (425 mg/70 kg BW) with HCQ (150 mg/70 kg BW) were injected along with those of the three drugs alone once daily for four weeks. Results: In alloxan induced diabetic rats, glibenclamide, metformin and their combination therapies reduced blood glucose level significantly but combination therapies are the most effective. Glibenclamide or metformin in combination with HCQ also significantly (P < 0.05) reduced the elevated levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol (LDL-C) level and increased high density lipoprotein cholesterol (HDL-C) level. Moreover, HCQ potentiates the liver glycogen synthesis of metformin or glibenclamide. Conclusion: Outcomes of this investigation indicate that combination of glibenclamide or metformin with HCQ improves glycemic control and provides additional metabolic benefits, not achieved
Journal of Scientific Research, 2012
The present study was designed to investigate the effects of combination drugs (metformin and ato... more The present study was designed to investigate the effects of combination drugs (metformin and atorvastatin) on long-term alloxan-induced diabetes with CVD in rats. In short-term alloxan-induced diabetic rats, metformin reduced significant amount of glucose in blood, but it had no significant effect on lipid profile. Atorvastatin significantly reduced TC, TG and LDL-C, whereas it increased significant amount of HDL-C. However, pathological changes of heart were not observed after short-term induction of alloxan in rats. In long-term induction of diabetes by alloxan, LV hypertrophy was observed and cardimyocyte size in rats was increased. Atorvastatin alone and in combination with metformin significantly reduced the LV hypertrophy, cardiomyocyte size, TC, TG and LDL-C level. They increased significant amount of HDL-C level and showed significant DPPH free radical scavenging activity. Present findings may suggest that treatment with combination therapy is more effective than mono-thera...
European Heart Journal
Background: Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovas... more Background: Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases including heart failure and cardiac hypertrophy. It is known that BNP levels are relatively higher in patients with chronic kidney disease with no heart disease; however, its mechanism remains unclear. Purpose: Our purpose is to determine whether a substance in the renal papillary tip is associated with BNP or not. Methods: We developed a BNP reporter mouse, pBNP-tdTomato transgenic (Tg) mice, with the DNA fragments of mouse BNP 1.1k promoter into the expression vector of tdTomato and six lines of Tg mice were screened. To evaluate the activation of BNP promotor in aged mice, we examined the expression of tdTomato in each of organs from pBNP-tdTomato Tg mice. We attempted to establish a primary culture of the pBNP-tdTomato-positive cells from kidneys of BNP reporter mice. We investigated the effects of an extract of the papillary tip of rat on the expression of BNP in cultured rat neonatal cardiomyocytes with the use of northern blot and ELISA measurement. The blood pressure, serum BNP and urine cGMP were measured in stroke-prone spontaneous hypertensive rats (SHR-SP) after the extract from the papillary tip was injected intraperitoneally. Ligation of the rats' left anterior descending coronary artery was performed, and the effects of extracts from the papillary tips of kidneys of heart failure rats were examined five days after the induction of myocardial infarction. Results: In addition to the expression of tdTomato in cardiomyocytes, we occasionally found that the BNP promoter was activated specifically in the papillary tip of the kidneys and was not accompanied by BNP mRNA expression. pBNP-tdTomato-positive cells appeared to be interstitial and were not observed in any area of the kidneys except for the papillary tip. No evidence was observed to show the existence of BNP isoform or other nucleotide expression than BNP from around the BNP promotor region. Unexpectedly, both the expression and the secretion of BNP increased in the primary cultured neonatal cardiomyocytes after the treatment with the extract of the renal papillary tip. We were able to culture papillary tip tissue containing tdTomato-positive cells for more than 2 months, but no proliferation was observed. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure accompanied by increasing serum BNP and urinary cGMP production in SHR-SP. Furthermore, the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes. Conclusions: These results suggest the interstitial cells in the renal papillary tip possess a substance that can stimulate BNP production and secretion from cardiomyocytes in vivo and in vitro.
Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypert... more Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.
Background and Purpose: We investigated the inhibitory effect and associated molecular mechanisms... more Background and Purpose: We investigated the inhibitory effect and associated molecular mechanisms of tolvaptan on angiotensin II (AngII)-induced aldosterone production in vitro and in vivo.
Aims GJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions.... more Aims GJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions. This study investigated whether GJB4 plays an important role in human heart disease and function.
The present study was designed to investigate the effects of combination drugs (metformin and ato... more The present study was designed to investigate the effects of combination drugs (metformin and atorvastatin) on long-term alloxan-induced diabetes with CVD in rats. In short-term alloxan-induced diabetic rats, metformin reduced significant amount of glucose in blood, but it had no significant effect on lipid profile. Atorvastatin significantly reduced TC, TG and LDL-C, whereas it increased significant amount of HDL-C. However, pathological changes of heart were not observed after short-term induction of alloxan in rats. In longterm induction of diabetes by alloxan, LV hypertrophy was observed and cardimyocyte size in rats was increased. Atorvastatin alone and in combination with metformin significantly reduced the LV hypertrophy, cardiomyocyte size, TC, TG and LDL-C level. They increased significant amount of HDL-C level and showed significant DPPH free radical scavenging activity. Present findings may suggest that treatment with combination therapy is more effective than mono-therapy for preventing diabetes with CVD in rats.
The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (ab... more The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (abbreviated as NSSE) on adrenaline-induced dyslipidemia and left ventricular hypertrophy (LVH) in rats. Intraperitoneal injection of adrenaline for two weeks induced dyslipidemia whereas injection of adrenaline for four weeks induced both dyslipidemia and LVH significantly, compared with normal rats. Injection of NSSE with different doses (0.5, 1 and 1.5 mg/kg body weight, BW) on adrenaline-induced dyslipidemic rats (AIDRs) for two weeks significantly reduced TC, TG and LDL-C and increased HDL-C compared with AIDRs and the most effective dose was 1.5 mg/kg BW. Treatment with NSSE (1.5 mg/kg BW) on AIDRs for eight weeks, significant anti-dyslipidemic effect was observed. Moreover, NSSE significantly increased free radical scavenging activity and attenuated the LVH and cardiomyocyte size compared with AIDRs. The results suggested that the antidyslipidemic, antioxidative and inhibitory effects of NSSE on LVH were closely resembled to that of atorvastatin, a most effective lipid lowering agent. Therefore, NSSE might be used as a therapeutic alternative or as a combination with drug in the treatment of dyslipidemia and LVH.
Background Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovasc... more Background Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.
Bangladesh Pharmaceutical Journal, 2015
ABSTRACT Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated th... more ABSTRACT Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated the hypothesis that the antidiabetic drugs glibenclamide and metformin, in combination with hydroxychloroquine (HCQ) offer additional protection for the pancreas against oxidative stress and produce hepatoprotective effect in alloxan-induced diabetic rats. Diabetes was induced in male Long-Evans rats by a single dose of alloxan (120 mg/kg; i.p.). Different groups of diabetic animals were treated with glibenclamide (10 mg/70 kg, i.p.), metformin (850 mg/70 kg, i.p.), HCQ (300 mg/70 kg, i.p.) and combination of both glibenclamide and metformin with HCQ, separately for a period of 28 days. Diabetic rats had significantly elevated levels of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), while catalase (CAT) and superoxide dismutase (SOD) activity were significantly reduced. Glibenclamide and metformin produced no significant effects on antioxidant enzymes but both showed significant (p<0.05) result in reducing SGOT and SGPT level in diabetic rats. In contrast, the combination of glibenclamide or metformin with HCQ showed better effect on up-regulation of CAT and SOD activity and down-regulation of SGOT and SGPT activity in comparison with the antidiabetic drug alone. These findings suggest that, HCQ potentiates the effect of glibenclamide and metformin to protect pancreas against oxidative stress and produce hepatoprotective effect in diabetic rats.
Pharmacology & Pharmacy, 2014
The aim of the current study is to investigate the effect of combination of glibenclamide; an ant... more The aim of the current study is to investigate the effect of combination of glibenclamide; an antidiabetic drug and simvastatin; a HMG-CoA reductase inhibitor on long-term (four weeks) alloxaninduced diabetes rats (ADRs). Methods: Alloxan (120 mg/kg body weight, BW) was injected intraperitonially (i.p.) in rats. At first alloxan (120 mg/kg BW) induced diabetic rats were treated with single dose of glibenclamide (1.2 mg/70kg BW) and simvastatin (10 mg/70kg BW) for two weeks. Then fixed dose combinations of glibenclamide (0.6 mg/70kg BW) and simvastatin (5 mg/70kg BW) were injected along with those of two drugs for four weeks. Results: At first it was found that glibenclamide reduced significant amount of glucose in blood, but it had no significant effect on lipid profile on short term (two weeks) ADRs. In contrast, simvastatin had no effect on blood glucose level, whereas it significantly reduced total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and increased significant amount of high density lipoprotein cholesterol (HDL-C). However, pathological changes of pancreas's Islets of Langerhans were observed only after long-term (four weeks) induction of alloxan in rats. The inhibitory effect of combination therapy on blood glucose, TC, TG and LDL-C level was higher than those of monotherapy alone on long term ADRs. In addition, treatment with combination therapy on long term ADRs showed higher amount of HDL-C level and super oxide dismutase and catalase enzyme activity than those with monotherapy. They also decreased serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) level. Administration of simvastatin recovered Langerhans cells from shrinkage whereas glibenclamide displayed slight recovery. But the * Corresponding author.
The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (ab... more The aim of this study was to investigate the inhibitory effect of Nigella sativa seed extract (abbreviated as NSSE) on adrenaline-induced dyslipidemia and left ventricular hypertrophy (LVH) in rats. Intraperitoneal injection of adrenaline for two weeks induced dyslipidemia whereas injection of adrenaline for four weeks induced both dyslipidemia and LVH significantly, compared with normal rats. Injection of NSSE with different doses (0.5, 1 and 1.5 mg/kg body weight, BW) on adrenaline-induced dyslipidemic rats (AIDRs) for two weeks significantly reduced TC, TG and LDL-C and increased HDL-C compared with AIDRs and the most effective dose was 1.5 mg/kg BW. Treatment with NSSE (1.5 mg/kg BW) on AIDRs for eight weeks, significant anti-dyslipidemic effect was observed. Moreover, NSSE significantly increased free radical scavenging activity and attenuated the LVH and cardiomyocyte size compared with AIDRs. The results suggested that the antidyslipidemic, antioxidative and inhibitory effects of NSSE on LVH were closely resembled to that of atorvastatin, a most effective lipid lowering agent. Therefore, NSSE might be used as a therapeutic alternative or as a combination with drug in the treatment of dyslipidemia and LVH.