The ameliorative effect of Heme Oxygenase System on early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

Alstonia scholaris (fam. Apocynaceae) is an indigenous plant used traditionally for the treatment of diabetes and associated complications. However the nephroprotective potential of the plant is not scientifically evaluated. Objective of the present was to investigate renal protective activity of hydroalcoholic extract of A. scholaris bark (HEAS) in streptozotocin (STZ)-induced early diabetic nephropathy in rats and to focus on its possible mechanism of action. Experimental diabetes was induced in Wistar rats using single intraperitoneal injection of streptozotocin (65 mg/kg). Animals were divided in five groups (n=6) and treated with 150 mg/kg and 300 mg/kg HEAS for 4 weeks. At the end of study period, fasting blood glucose, blood urea nitrogen (BUN), serum creatinine, total proteins, serum albumin, serum insulin and glycosylated haemoglobin, superoxide dismutase, catalase, reduced glutathione and MDA in kidney were evaluated. Urine was analyzed for albumin, total proteins and creatinine clearance. Kidney and pancreas were subjected for histopathology. Significant decrease in fasting blood glucose, creatinine, albumin, BUN, total proteins and urinary total proteins was observed. Significant improvement in serum insulin, glycosylated Hb, oxidative stress parameters of kidney including superoxide dismutase, catalase and reduced glutathione has been observed in HEAS treated diabetic rats. Histopathology of kidney and pancreatic tissues showed structural improvement. Present study has revealed that HEAS prevented the progression of diabetic nephropathy in STZ-diabetic rats by improving the disturbed glucose homeostasis and by amelioration of renal oxidative stress.

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Sanguinarine Ameliorates Diabetic Nephropathy in Rats through Nuclear Factor-Kappa B and Nuclear-Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathways

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:398-404 ◽

2021 ◽

Vol 19 (4) ◽

pp. 398-404

Author(s):

Jiao Zhong

Keyword(s):

Diabetic Nephropathy ◽

Heme Oxygenase ◽

Nuclear Factor Kappa B ◽

Kidney Injury ◽

Diabetic Rats ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Related Complication ◽

Nuclear Factor Kappa

Alkaloids - derived from natural plants - were widely used for therapy in diabetes or diabetes-related complications. Sanguinarine, a benzophenanthridine alkaloid derived from Sanguinaria canadensis, has been identified as a potential drug for type 2 diabetes. However, the role of sanguinarine on diabetes-related complication, diabetic nephropathy, has not been reported yet. In a rat model of diabetic nephropathy we have demonstrated increased levels of 24 h urinary proteins, serum creatinine, and blood urea nitrogen, as well as series of degenerative changes in the kidney tissues. Oral administration with sanguinarine to diabetic rats diminished kidney injury markers and improved the tissue morphology. Furthermore, sanguinarine attenuated increase in the levels of tumor necrosis factor-α and interleukin-6 through downregulation of phosphonuclear factor-kappa B and phosphorylated inhibitor of nuclear factor kappa-B. Lastly, sanguinarine reversed the effects of streptozotocin on levels of reactive oxygen species, malonaldehyde, superoxide dismutase, and glutathione peroxidase through upregulation of nuclear factor erythropoietin-2-related factor 2, heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in kidney of rats. In conclusion, sanguinarine ameliorates diabetic nephropathy in rats through inactivation of nuclear factor-kappa B and activation of nuclear-factor erythroid 2-related factor 2 pathways.

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Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.12373 ◽

2015 ◽

Vol 42 (4) ◽

pp. 361-368 ◽

Cited By ~ 14

Author(s):

Anita Barzegar-Fallah ◽

Houman Alimoradi ◽

Firouzeh Asadi ◽

Ahmad Reza Dehpour ◽

Mojgan Asgari ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Diabetic Rats ◽

Early Diabetic Nephropathy

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Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

BioMed Research International ◽

10.1155/2014/105214 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Mohamed A. Morsy ◽

Salwa A. Ibrahim ◽

Entesar F. Amin ◽

Maha Y. Kamel ◽

Soha A. Abdelwahab ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Protective Effect ◽

Histopathological Examination ◽

Electron Microscopic Examination ◽

Diabetic Rats ◽

Electron Microscopic ◽

Podocyte Injury ◽

Stage Renal Disease ◽

End Stage ◽

Early Diabetic Nephropathy

Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-α, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury.

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