Betulinic acid abates N-nitrosodimethylamine-induced changes in lipid metabolism, oxidative stress, and inflammation in the liver and kidney of Wistar rats.

Abstract

N-nitrosamines have been linked with cancer in humans due to their presence in drinking water and diets. This study evaluated the role of betulinic acid (BA) in abating oxidative stress, inflammation, and hyperlipidemia in rats treated with N-nitrosodimethylamine (NDMA). Twenty-four male rats were assigned into four equal groups. Group I served as the control, Group II received BA (25 mg/kg), Group III received NDMA (5 mg/kg) and, Group IV received BA (25 mg/kg) and NDMA (5 mg/kg). Results showed that the administration of NDMA significantly (p < 0.05) elevated malondialdehyde in the liver and kidney relative to controls. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, and the level of glutathione were significantly (p < 0.05) decreased by NDMA, while treatment with BA elevated the activities of these enzymes in the liver and kidney. The BA lowered serum interleukin-6 and tumor necrosis factor-alpha levels against the NDMA effect. Furthermore, NDMA increased hepatic and renal triglyceridewhile phospholipids levels were decreased. NDMA significantly modulated the activities of drug-metabolizing enzymes (aniline hydroxylase, aminopyrine-N-demethylase, and uridyldiphosphoglucuronyltransferase), while BA was able to restore these enzymes to values close to controls. Histology revealed the presence of infiltration and fibroplasia in the liver, while cortical degeneration was noticed in the kidney in NDMA-administered rats. These lesions were reduced in the NDMA rats treated with BA. The findings suggest that BA improves NDMA-induced damage in the liver and kidney of rats through reactions that can be linked with antioxidant, anti-inflammatory, and lipid-lowering pathways.