rotenone toxicity in male and female albino rats in the route of parkinson’s disease modeling

Background: rotenone is commonly used for parkinson’s disease (pd) experimental models based on selective neurodegeneration of midbrain dopaminergic neurons and motor dysfunctions. meanwhile, rotenone is a toxic compound that causes high mortality, requiring a more significant number of experimental animals. differences between male and female species in response to rotenone toxicity were reported, stating higher sensitivity in males than in females. in spite of the suggested various doses of rotenone, it is essential to regulate its dosage, especially when male and female species are involved in the experiments. the present study aimed to determine the optimal dose and duration of chronic rotenone injections in rats to achieve a relatively lower mortality rate.methods: male and female albino rats were treated with moderate (2 mg/kg/day) and low (0.3-0.5 mg/kg/day) rotenone at different regimens. the brain (substantia nigra, striatum) and spinal cord were analyzed for neurodegeneration using h&e staining. the body weight and mortality of rats were monitored on a daily basis.results: comparative studies indicated that low doses of systemic rotenone injections were less toxic to females than to male rats. female rats were more sensitive to chronic rotenone exposures, indicated by aggressive and anxious behavior. nonetheless, the lower mortality rate in female than that in male rats suggested distinct physiological mechanisms to play a role in reduced rotenone toxicity in female rats.conclusion: these observations should be considered when male and female rats are involved in pd modeling. the diverse responses to neurotoxin are essential to provide a valid platform for further treatment schemes and clinical outcomes.