Rosmarinic acid attenuates arsenic-associated neurotoxicity in mice: Behavioral, biochemical, and histopathological evidence.
Abstract
Background
Arsenic has a significant role in the pathogenesis of neurological disorders. Rosmarinic acid (RA) is a naturally occurring phenolic compound known for its antioxidant and anti-inflammatory activities. The present study aims to explore the effects of RA against neurotoxicity caused by sodium arsenite (SA) exposure in mice.
Methods
Forty-two male mice were randomly assigned to six equal groups: control group, RA group (50 mg/kg, orally for a period of 14 days), SA group (50 ppm via drinking water for 8 weeks), and treatment groups were co-treated with 50 ppm of SA for 8 weeks, along with 10, 25, and 50 mg/kg of RA, respectively during the final 14 days of the study. On the last week of the study, behavioral tests were performed. In addition, at the end of the study, biochemical assessments and histopathological study were conducted.
Results
The findings indicated that SA significantly impairs locomotor activity, neuromuscular function, motor coordination, and cognitive performance. SA markedly increased the levels of thiobarbituric acid reactive substances, nitric oxide, and tumor necrosis factor-α and the expression of arsenite methyltransferase (AS3MT) and sirtuin 3 (SIRT3) proteins in the brain cortex and diminished the levels of total thiol, and the enzymatic activities of superoxide dismutase, glutathione peroxidase, and catalase. In addition, treatment with SA induced histological damage in the hippocampus. Conversely, treatment with RA improved SA-associated behavioral, biochemical, and histopathological impairments.
Conclusions
These findings demonstrate that RA exhibits potential antioxidant and anti-inflammatory properties, providing a protective effect against SA-associated neurobehavioral toxicity in mice, which may be mediated by the upregulation of AS3MT and SIRT3 proteins. However, further mechanistic and clinical studies are required to verify and extend these findings.