Ameliorating Effects of Silymarin-Loaded PLGA on Acetaminophen-Induced Nephrotoxicity in Mice

Abstract

Background: Silymarin (SM) has beneficial effects against numerous different types of toxicants. However, the low bioavailability of SM has limited its therapeutic effects. Objectives: This study investigated the toxic effect of nanostructured SM (NSM) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on nephrotoxicity induced by acetaminophen (APAP) in mice. Methods: The encapsulation of SM in PLGA was performed by the solvent evaporation method. A total of 48 NMRI mice were used in this experimental study. The mice were pretreated with SM or NSM (5 mg/kg) for 7 days, and APAP (300 mg/kg) was administrated on the 6th day. The serum levels of blood urea nitrogen, creatinine, and uric acid were measured. Histological assessment and messenger ribonucleic acid expression of BAX and BCL-2 genes were also carried out. Results: The APAP destroyed the structure of the renal tissue and significantly reduced renal weight and glomerulus diameters (P < 0.01). The APAP also caused a significant increase in the serum levels of biochemical markers (P < 0.001) and expression of the BAX/BCL-2 ratio in the renal tissue (P < 0.001). The NSM could improve the renal structure and significantly increase renal weight and glomerulus in the APAP-intoxicated mice. The NSM significantly reduced the level of the biochemical tests and the BAX/BCL-2 ratio in the APAP-treated group (P < 0.01). Conclusions: The obtained data indicate that PLGA effectively enhances the nephroprotective effects of SM on nephrotoxicity induced by APAP.