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....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 with either glibenclamide or metformin alone.展开更多
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) alloxan-induced diabetes rats (ADR...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) alloxan-induced diabetes rats (ADRs). Methods: Alloxan (120 mg/kg body weight, BW) was injected intra-peritonially (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 combination therapy showed complete recovery of Langerhans cells as compared with diabetic rats. Conclusion: Our present findings suggest that treatment of glibenclamide in combination with simvastatin may be more effective than mono-therapy for preventing diabetes in rats. It may also suggest that this combination may have some beneficial effects on reducing cardiovascular risks from long term diabetes in rats.展开更多
Present research was designated to investigate the hypoglycemic, hypolipidemic and antioxidant activity of the combination of pioglitazone and atorvastatin on long-term alloxan-induced diabetes rats (AIDRs). The exper...Present research was designated to investigate the hypoglycemic, hypolipidemic and antioxidant activity of the combination of pioglitazone and atorvastatin on long-term alloxan-induced diabetes rats (AIDRs). The experiments were carried out to determine blood glucose level, lipid profile, free radial scavenging activities, superoxide dismutase (SOD) and catalase in liver tissue. In addition, left ventricular (LV) hypertrophy and cardiomyocyte size were also determined by histological analysis. It was found that in short-term induction, pioglitazone significantly reduced the blood glucose level without having any considerable effect on lipid profile and antioxidant enzymes (SOD and catalase) in rats. On the other hand, atorvastatin significantly reduced total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) with marked increase in the level of high density lipoprotein cholesterol (HDL-C) and improved activity of SOD and catalase enzymes. However, pathological changes of heart and pancreas were not observed after short-term exposure to alloxan in rats. Long-term diabetes induction resulted in LV hypertrophy and prominent shrinkage of islets of Langerhans cells. Treatment with atorvastatin in combination with pioglitazone significantly reduced the LV hypertrophy, TC, TG and LDL level whereas they noticeably increased HDL level, DPPH (1,1-Diphenyl-2-picryl-hydrazyl) free radical scavenging activity, SOD and catalase activity with satisfactory recovery of Langerhans cells. The result demonstrated that combination therapy was more effective than that of mono-therapy for preventing diabetes with cardiovascular diseases (CVD) in rats.展开更多
文摘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 with either glibenclamide or metformin alone.
文摘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) alloxan-induced diabetes rats (ADRs). Methods: Alloxan (120 mg/kg body weight, BW) was injected intra-peritonially (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 combination therapy showed complete recovery of Langerhans cells as compared with diabetic rats. Conclusion: Our present findings suggest that treatment of glibenclamide in combination with simvastatin may be more effective than mono-therapy for preventing diabetes in rats. It may also suggest that this combination may have some beneficial effects on reducing cardiovascular risks from long term diabetes in rats.
文摘Present research was designated to investigate the hypoglycemic, hypolipidemic and antioxidant activity of the combination of pioglitazone and atorvastatin on long-term alloxan-induced diabetes rats (AIDRs). The experiments were carried out to determine blood glucose level, lipid profile, free radial scavenging activities, superoxide dismutase (SOD) and catalase in liver tissue. In addition, left ventricular (LV) hypertrophy and cardiomyocyte size were also determined by histological analysis. It was found that in short-term induction, pioglitazone significantly reduced the blood glucose level without having any considerable effect on lipid profile and antioxidant enzymes (SOD and catalase) in rats. On the other hand, atorvastatin significantly reduced total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) with marked increase in the level of high density lipoprotein cholesterol (HDL-C) and improved activity of SOD and catalase enzymes. However, pathological changes of heart and pancreas were not observed after short-term exposure to alloxan in rats. Long-term diabetes induction resulted in LV hypertrophy and prominent shrinkage of islets of Langerhans cells. Treatment with atorvastatin in combination with pioglitazone significantly reduced the LV hypertrophy, TC, TG and LDL level whereas they noticeably increased HDL level, DPPH (1,1-Diphenyl-2-picryl-hydrazyl) free radical scavenging activity, SOD and catalase activity with satisfactory recovery of Langerhans cells. The result demonstrated that combination therapy was more effective than that of mono-therapy for preventing diabetes with cardiovascular diseases (CVD) in rats.