Analysis of sex difference in strychnine-intoxicated rat based on the combination of metabolic kinetics and metabolomics

Significant sex-specific difference exists between strychnine pharmacokinetics and metabolomics of male and female rats, potentially due to the differential expression of ABC transporter expression, pyrimidine metabolism and linoleic acid metabolism. These findings provide an important reference for sex-specific clinical management of strychnine toxicity. Strychnine is a medication used for the treatment of muscle weakness and visual issues. However, it affects males and females differently. If dosing is not customized according to sex, it may lead to toxicity. Therefore, we explored the mechanisms underlying the toxic effects of strychnine in male and female rats (both intact and gonadectomized). We found that female rats showed higher blood drug levels. Moreover, the peak blood drug concentrations of both male and female rats decreased after gonadectomy. Additionally, sex-specific differences were observed in the expression of ABC transporter expression, pyrimidine metabolism and linoleic acid metabolism. These differences may explain why strychnine affects male and female rats differently.