Leucine Mitigates Diabetic Nephropathy via Its Antioxidant Effect and Modulation of TGF-β/SMAD-3 Signalling Pathway in Streptozotocin-Induced Diabetic Rats

Abstract

Background/Objectives Diabetic nephropathy (DN) is the main contributor to the incidence of end-stage renal disease and kidney failure. This research aims to explore the curative effect of leucine in the DN rat model. Methods 40 male rats were sorted into four equal groups. Group I acted as the control group. Group II was given leucine (1.35g/kg orally, once daily) for 8 weeks. Group III administered a single intraperitoneal injection of Streptozotocin (STZ) (45 mg/kg, i.p.). Group IV was administered leucine following the diagnosis of diabetes for a duration of 8 weeks. In this study, samples were obtained from blood and renal tissue for biochemical assessments, evaluation of redox state, real-time polymerase chain reaction (RT-PCR) analysis of L-type amino acid transporter 1 (LAT1) and suppressor of Mothers against Decapentaplegic (SMAD3) genes, as well as histological examination. Results Leucine supplementation to diabetic rats markedly reduced alterations in markers of kidney function. Furthermore, a reduction in redox markers and inflammatory cytokines was observed in tissues isolated from the leucine-treated diabetic group compared with diabetic rats. Additionally, the expression of the SMAD3 gene, mTOR, and c-JNK protein in renal tissue was significantly reduced in the leucine-diabetic group compared with the diseased group. Conversely, LAT1 tissue expression was upregulated in the leucine-diabetic group. Conclusion The administration of leucine inhibited renal damage by reducing activation of the profibrotic transforming growth factor beta-1 TGF-β/Smad3 signalling pathway.