Hepatorenal protective effect of berberine-loaded Ag-ZnO nanoparticles in mitigating carbon tetrachloride (direct) and alloxan-induced oxidative stress (indirect) in albino rat models.

Hepatorenal toxicity stems from chronic oxidative stress (OS) generated from mechanisms underlying chemical or metabolic injury. The present study investigates the hepatorenal toxicity induced by carbon tetrachloride (CCl4) and alloxan, and the hepatorenal-protective potential of Berberine-loaded (BBR) silver-zinc oxide nanoparticles (Ag-ZnO NPs) in mitigating the damage. The characterization of synthesized NPs was performed using UV-vis spectroscopy, XRD, FTIR, and TEM, DLS, zeta potential and TGA analysis. Synthesized NPs showed characteristic physicochemical properties in terms of size, shape and crystallinity. In vivo studies demonstrated that administration of CCl4 directly altered the levels of hepatic and renal function parameters, attributed to excessive generation of ROS compromising the antioxidant defense system, while alloxan directly targeted pancreatic β-cells, elevating blood glucose levels, generating ROS, which caused secondary hepatic and renal damage pertaining to persistent hyperglycemia. The lipid profile was also disrupted in both models, with increased levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), while reducing high-density lipoprotein (HDL) levels. Histopathological analysis also revealed significant changes in liver and kidney structure. BBR-loaded Ag-ZnO NPs were found to restore the hepatic and renal function parameters better in the CCl4 induced toxicity model, owing to their anti-oxidant and anti-inflammatory activity. Serum levels of TC, TG, and LDL were reduced while HDL levels were increased. Furthermore, the endogenous antioxidant defense system was restored to a greater extent. The structural integrity of liver and kidneys was also restored to normal. To conclude, the BBR-loaded Ag-ZnO NPs exhibited an exceptional potential in overcoming oxidative stress-induced direct toxicity by CCl4, as compared to indirect (metabolic) toxicity induced by alloxan.