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Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes.

ABSTRACT: Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40?mg/kg) or NA (230?mg/kg) followed by STZ (65?mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

SUBMITTER: Bayrasheva VK

PROVIDER: S-EPMC5206480 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes.

Bayrasheva Valentina K VK Babenko Alina Yu AY Dobronravov Vladimir A VA Dmitriev Yuri V YV Chefu Svetlana G SG Pchelin Ivan Yu IY Ivanova Alexandra N AN Bairamov Alekber A AA Alexeyeva Nina P NP Shatalov Ivan S IS Grineva Elena N EN

Journal of diabetes research 20161220

Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. <i>Aim</i>. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrecto ...[more]

PMID: 28090542

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Project description:Background:Male hypogonadism is associated with type II diabetes mellitus due to testicular dysfunction. Medicinal plants have received considerable attention for the management of diabetes and its complications. Objective:The aim of present study was to evaluate the anti-diabetic and protective influence of Crocin on testopathy in diabetic rats. Materials and Methods:In this experimental study, type II of diabetes mellitus was induced by high-fat diet and low dose of streptozotocin. Male Wistar rats (8 weeks, 150-200 gr, 18 rats; n= 6 per group) were divided into a control group (standard diet), diabetic group (streptozotocin+high-fat diet), and treatment group (High-fat diet+streptozotocin+Crocin at 20 mg/kg/day, i.p. for 60 days). After 60 days, animals were euthanized, testis and epididymis were dissected, and weights of testes and sperm count were analyzed. Hematoxylin-eosin-stained was done for histopathological examination. Blood samples were collected for the assessment of serum glucose and cholesterol. Results:High-fat diet and streptozotocin significantly increased the serum glucose and cholesterol levels as compared to the control group (p ? 0. 001). Moreover, there was a significant decrease in the weight of right (p= 0.008) and left testes (p ? 0. 001) and also the total sperm count (p= 0.023) in the diabetic group compared with the control group. Current results also identified that type II diabetes mellitus induced degeneration in the morphology of seminiferous tubules. Application of Crocin could significantly decrease serum glucose and cholesterol levels (p= 0.003). Furthermore, Crocin treatment significantly increased the weight of the right (p= 0.026) and left (p= 0.014) testes and total sperm count (p= 0.000). Also, Crocin could attenuate the pathological changes of the testes in the treatment group. Conclusion:Present findings concluded that Crocin treatment improved diabetic testopathy and impairment of seminiferous tubules induced by high-fat diet and streptozotocin.

Dataset Information

Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes.

Publications

Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes.

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