Saroglitazar suppresses KIM-۱ and type IV collagen in high fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats

Objective(s): Nephropathy is the most common comorbidity linked to T۲D. The present study aimed to examine the potential of saroglitazar in the context of a high-fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats. Materials and Methods: Molecular docking simulation investigations were conducted on the ligand-binding region of type IV collagen and Kidney injury molecule-۱ (KIM-۱), using saroglitazar and fenofibrate as the subjects.  The rats were fed either a conventional rodent diet or a high-fat diet ad libitum for two weeks. Following a two-week period, the rats given an HFD were administered with a low-dose of STZ (۳۵ mg/kg, IP). Rats with experimentally induced diabetes were categorized into five groups: normal control; diabetic control; HFD+STZ+saroglitazar (۲ mg/kg); HFD+STZ+saroglitazar (۴ mg/kg); HFD+STZ+fenofibrate (۱۰۰ mg/kg) treated orally for ۲۱ days with continuation on HFD. After ۲۱ days, rats were kept on fasting overnight, blood and urine was acquired for various biochemical analysis. Animals were sacrificed, and kidney tissues were removed for histopathological studies. Results: In-silico investigation showed a substantial affinity between saroglitazar and fenofibrate with KIM-۱ and type IV collagen. Saroglitazar produced a significant (P<۰.۰۱) reduction in weight of the body, serum blood sugar, albumin, creatinine, and BUN levels. Further, saroglitazar significantly (P<۰.۰۱) reduced the KIM-۱ and type IV collagen levels in the urine of diabetic rats.  Histopathological results showed improvement in tubular degeneration, necrosis, and dilatation of Bowman’s space in kidney tissue. Conclusion: Saroglitazar attenuated renal injury by improving renal function in HFD+STZ-induced DN in Wistar rats.

Keywords:

Diabetic nephropathy , Fenofibrate , Kidney injury Molecule-۱ , Saroglitazar , Streptozotocin , Type IV collagen