An experimental study of exenatide effects on renal injury in diabetic rats

Abstract

Purpose To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats. Methods Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined. Results Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05). Conclusions Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form

“…SOD is a crucial enzyme widely existing in the body. Its content can mirror free radicals scavenging ability [ 63 ]. The SOD could be postulated as the start of sparks for antioxidant cascade by superoxide anion detoxification into hydrogen peroxide [ 64 ].…”

Renoprotective Effects of Incretin-Based Therapy in Diabetes Mellitus

“…Moreover, Liang et al in 2020 provided further direct evidences indicating liraglutide protects against diabetic nephropathy by downregulation of TXNIP (thioredoxin-interacting protein), which acts as an oxidative stress inducer in male high fed diet mice [ 46 ]. Similarly, Wang and coworkers reported that exenatide exerts renoprotective effects by suppressing oxidative damage in diabetic rats [ 47 ]. Therefore, it has been hypothesized that improvement of renal function and reduction in albuminuria might be associated with the antioxidant properties of these agents [ 48 – 50 ].…”

“…More recently, Cappetta and colleagues showed that DPP-4 inhibition might reduce the progression of DN by suppressing the inflammatory mediators, such as TNF- α , IL-1 β , IL-6, and MCP-1 in rats [ 57 ], suggesting a potential immunomodulatory effect for these drugs. In addition, Wang and colleagues in 2019 reported that exenatide provided protective effects against DN via alleviating the inflammatory responses in diabetic rats [ 47 ]. They found that exenatide reduced inflammatory markers such as TNF- α , IL-6, CRP, and CCL-5 (chemokine C-C motif ligand 5) in renal tissues [ 47 ].…”

“…In addition, Wang and colleagues in 2019 reported that exenatide provided protective effects against DN via alleviating the inflammatory responses in diabetic rats [ 47 ]. They found that exenatide reduced inflammatory markers such as TNF- α , IL-6, CRP, and CCL-5 (chemokine C-C motif ligand 5) in renal tissues [ 47 ]. Moreover, Muskiet et al in an extensive clinical study demonstrated renoprotective effects of incretins and suggested that they provide these beneficial effects via anti-inflammatory properties [ 58 ].…”

GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Clinical Outcomes to Mechanisms

“…Zitman-Gal et al revealed that liraglutide attenuated the phosphorylation of JAK2 and STAT3 in AGE-stimulated endothelial cells and the kidney of db/db mice ( Zitman-Gal et al., 2019 ). Furthermore, it has been reported that the administration of exenatide attenuates the renal inflammation index, including reducing the TNF-α, IL-6, hsCRP, and CCL5 levels, in STZ-induced diabetic rats by increasing the superoxide dismutase and decreasing malondialdehyde levels ( Wang et al., 2019 ). Taken together, the prevention of oxidative stress and inflammation is a key mechanism for the renoprotective effects of GLP-1RAs.…”