The Effects of Co-administration of Lithium and Vitamin E on Hepatic Oxidative Status in Aged Male and Female Rats: Biochemical and Histomorphological Evaluations.

Lithium serves as an effective mood stabilizer for bipolar disorder, especially in older adults, but high doses or prolonged use may lead to toxicity. Here, we assessed the hepatic toxicity of lithium chloride (LiCl) in aged male and female rats and examined whether vitamin E as an antioxidant can mitigate lithium's toxic effects. Forty-eight Wistar rats aged 16-18 months were divided into four equal groups for each sex (n = 6 each): a placebo group receiving vehicle (almond oil), a vitamin E group receiving 100 mg/kg of vitamin E every other day, a lithium chloride (LiCl) group receiving 50 mg/kg/day of LiCl, and a combined LiCl + vitamin E group (LiCl + Vit E) receiving both treatments for four weeks. Serum lithium levels, ALT, AST, and ALP enzymes were measured. Liver tissues were assessed for malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, along with histopathological changes. Long-term lithium administration significantly elevated serum lithium levels in aged male and female rats. Lithium-induced hepatotoxicity was characterized by raising serum ALP and tissue MDA levels and reducing SOD and GPx activity. However, ALT and AST changes were sex-dependent, with no significant alterations in female rats. Vitamin E co-treatment significantly reduced serum lithium concentrations, improved serum markers, and histopathological indicators of liver fibrosis caused by lithium toxicity. Also, by preventing tissue oxidative stress, vitamin E enhanced liver antioxidant capacity and restored SOD and GPx activity in aged rats. These findings suggest that vitamin E may serve as an effective antioxidant and antifibrotic agent in the course of lithium therapy, potentially mitigating complications in elderly patients by improving lithium clearance and liver function.