The ameliorative effect of lycopene and grape seed proanthocyanidins extract against streptozotocin-induced diabetic nephropathy in rats

The purpose of this study was to investigate the effects of lycopene (Lyc) and grape seed proanthocyanidin extract (GSPE) in a rat model of experimental diabetic nephropathy (DN) produced by streptozotocin (STZ). Animals with DN were treated with Lyc, GSPE, or a combination of both. Serum glucose, urea, creatinine, retinol-binding protein (RBP), and urinary protein levels were measured. Renal oxidative stress markers, inflammation and fibrosis -related genes and histopathological changes were analyzed. Molecular docking simulations assessed interactions between Lyc/GSPE components and DN-associated proteins (TGFβ1, NFκB, MCP1, MMP9). Administration of Lyc and GSPE significantly restored high levels of serum glucose, urea, creatinine and RBP as well as urinary proteins in DN rats. There was also a better renal oxidative/antioxidant state as evident in enhanced catalase, superoxide dismutase and glutathione peroxidase activity along with the reduced level of malondialdehyde. The co-treatment with Lyc and GSPE significantly downregulated the renal expression of inflammation and fibrosis -related genes ( TGFβ1, NFκB, MCP1, and MMP9 ). This was confirmed by molecular docking analysis. This cotreatment also reduced fibrosis, infiltration of inflammatory cells and overall level of renal tissue damage. These results underscore nephroprotective effects of Lyc and GSPE, primarily by improving antioxidant, anti-inflammatory, and anti-fibrotic activities. Hence, such natural compounds could be beneficial for use as treatment agents of acute diabetic nephropathy.