Hepatoprotective potential of Vernonanthura polyanthes against doxorubicin-induced oxidative stress in a murine model

• Vernonanthura polyanthes can promote oxidative stress in hepatocytes at high doses. • Conversely, V. polyanthes reduced doxorubicin (DXR)-induced lipid peroxidation. • V. polyanthes molecules are promising candidates for reducing the side effects of DXR. The present study aimed to evaluate the redox activity of Vernonanthura polyanthes leaf aqueous extract ( Vp LAE) and its n-butanol fraction (n-BF) in mouse liver in the absence or in the presence of doxorubicin (DXR). For this, the concentration of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) were determined in the liver of Swiss Webster mice (n = 5 animals per group). Immunohistochemical analyses on hepatocytes labeled with anti-4-hydroxynonenal (4HNE) were also performed to confirm the decrease in lipid peroxidation in animals treated with DXR and Vp LAE or n-BF. MDA levels and GST activity increased in the livers of mice that received just Vp LAE at a dose of 1000 mg/kg compared with the negative control. Moreover, n-BF alone increased CAT activity at 250 mg/kg, SOD and GST at 1000 mg/kg, and MDA at 250, 500, and 1000 mg/kg. These data indicate that Vp LAE or n-BF alone can promote oxidative stress in hepatocytes. In contrast, when Vp LAE was associated with DXR in a pre-treatment regimen, or when n-BF was associated with DXR in co- or pre-treatment regimens, MDA levels decreased, suggesting a protective effect against DXR-induced damage. The decrease in 4HNE labeling in the livers of mice treated with DXR and Vp LAE or n-BF confirmed that pre-treatment with Vp LAE or pre- and co-treatments with n-BF reduced DXR-induced lipid peroxidation. In conclusion, Vp LAE and n-BF could present a dual behavior, promoting oxidative stress in hepatocytes in the absence of DXR or reducing oxidative stress in the livers of mice treated with DXR. This shift in perspective motivates future studies of Vp LAE and n-BF as promising candidates to overcome DXR-induced hepatotoxicity.