Phyllanthin identified from Phyllanthus amarus attenuates arsenite-induced liver and kidney damage: Role of NF-kB pathway inhibition.

Sodium arsenite is a common and highly toxic inorganic arse-nic compound that causes liver and kidney damage. Phyllanthus amarus is well known for its protective effects on these organs. This study aimed to identify the active phytoconstituents of the methanolic extract of P. amarus (PAME) and to explore their effects on arsenite-induced liver and kidney toxicity in experi-mental rats. The standardization of P. amarus extract was performed using high-performance liquid chromatography (HPLC). Male Wistar rats developed liver and kidney toxicity after daily oral administration of sodium arsenite (5 mg/kg) for 4 weeks. The rats were simultaneously given coenzyme Q10 (CoQ10; 10 mg/kg) or PAME (50, 100, and 200 mg/kg). Results showed that HPLC analy-sis detected phyllanthin at a retention time of 25.41 minutes with an area of 71.84%. Arsenite treatment caused a significant (p<0.001) increase in hepatic enzymes (ALT, AST, and ALP), renal markers (BUN, uric acid, and creatinine), and direct and total bilirubin in the serum. It also significantly increased hepatic and renal levels of malondialdehyde, nitric oxide, NF-κB p65, interleukins (ILs), and TNF-α (p<0.001), while decreasing hepatic antioxidant enzymes (GSH and SOD) and overall hepatic antioxidant capacity. Notably, P. amarus extract (200 mg/kg) markedly (p<0.001) mitigated arsenite-induced changes in these serum markers, oxidative stress indicators, NF-kB p65, and inflammatory cytokines. It also improved the structure of liver and kidney tissues, maintained cellular ar-chitecture, and reduced necrosis and inflammation. In conclusion, these results suggest that phyllanthin from P. amarus protects against arsenite-induced liver and kidney damage by inhibiting NF-κB activation, reducing inflammatory cyto-kine release, and decreasing oxidative and nitrosative stress, thereby enhancing overall antioxidant capacity. Therefore, P. amarus extract may be a promising treatment for pesticide-related liver and kidney injuries in rats.