Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats
American Journal of Internal Medicine
Volume 6, Issue 6, November 2018, Pages: 161-169
Received: Sep. 16, 2018; Accepted: Oct. 11, 2018; Published: Nov. 5, 2018
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Ye Feng, Department of Endocrinology and Metabolism Disease, the First Affiliated Hospital, Zhejiang University, Hangzhou, China
Chengjiang Li, Department of Endocrinology and Metabolism Disease, the First Affiliated Hospital, Zhejiang University, Hangzhou, China
Yuehuan Liu, Zhejiang Center of Laboratory Animals, Zhangjiang Academy of Medical Sciences, Hangzhou, China
Long Zhang, Department of Endocrinology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, China
Zhe Zhang, Department of Endocrinology and Metabolism Disease, the First Affiliated Hospital, Zhejiang University, Hangzhou, China
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As a dipeptidyl peptidase-4 (DPP-4) inhibitor used in diabetes mellitus (DM) therapy, saxagliptin (Saxa) has been reported an additional protective benefit of diabetic nephropathy (DN), which might be independent of its glucose-lowering effect. However, the mechanism is not fully understood. In this study, STZ-induced DM rat model received a placebo or Saxa (10mg or 20mg/kg, 8-10 rats in each group). Blood glucose, serum lipid, creatinine, blood urea nitrogen, as well as urine protein and albumin concentration, were examined. Gene expression and protein level of advanced glycation end products (AGEs) and their receptor (RAGE) were also tested. Moreover, markers for oxidative stress and antioxidant ability were determined. The results showed moderate albuminuria in diabetic rats was attenuated after Saxa treatment, consistent with morphological improvement supported by histological analysis. Both AGEs and RAGE levels were elevated in DM group but reduced after Saxa administration. Furthermore, the level of malondialdehyde (MAD), Caspase 3, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney were much lower in Saxa group compared with DM group, indicating the oxidation and apoptosis in DM were ameliorated by Saxa. On the other hand, markers of antioxidation such as total antioxidation capability (TAOC), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), had a relevant increase, suggesting enhanced antioxidation in the kidney. In conclusion, these findings show that Saxa possesses anti-oxidative activity to ameliorate diabetic renal damage, which is related to the regulation of the AGEs-RAGE axis.
Dipeptidyl Peptidase-4 Inhibitor, Diabetes Mellitus, Advanced Glycation End Products, AGE Receptor, Oxidative Stress
To cite this article
Ye Feng, Chengjiang Li, Yuehuan Liu, Long Zhang, Zhe Zhang, Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats, American Journal of Internal Medicine. Vol. 6, No. 6, 2018, pp. 161-169. doi: 10.11648/j.ajim.20180606.13
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