Selenium Ameliorates Modafinil-Induced Male Reproductive Toxicity via Modulation of PI3K/Akt/NF-ҡB Pathway:...

Area of Science:

• Reproductive Toxicology
• Pharmacology
• Nutritional Science

Background:

• Modafinil (MOD) is a widely used nootropic with expanding applications.
• Limited research exists on MOD's adverse effects on male reproductive health.
• Understanding MOD's reproductive toxicity is crucial due to its increasing use.

Purpose of the Study:

• To investigate the dose-dependent reproductive toxicity of Modafinil in male rats.
• To evaluate the potential protective effects of selenium (Se) against MOD-induced toxicity.
• To elucidate the underlying biochemical and molecular mechanisms of MOD's reproductive effects.

Main Methods:

• Adult male rats were treated with varying doses of MOD and/or Se.
• Evaluated parameters included erectile function, sperm quality, reproductive hormones (Testosterone, LH, FSH), oxidative stress markers (MDA, SOD, TAC), and inflammatory markers (NO, iNOS).
• Molecular analyses included pathway assessment (PI3K/Akt/NF-ҡB) and molecular docking, alongside histopathological and ultrastructural examinations.

Main Results:

• Modafinil administration significantly impaired erectile function and sperm quality.
• MOD altered reproductive hormone levels and induced oxidative stress and inflammation.
• Selenium co-administration, particularly at 0.2 mg/kg/day, significantly ameliorated MOD-induced reproductive damage and normalized key biochemical markers.

Conclusions:

• Modafinil exerts dose-dependent toxicity on male reproductive function.
• Selenium demonstrates a protective role against Modafinil-induced reproductive toxicity.
• Selenium may represent a viable therapeutic approach to counteract Modafinil's adverse reproductive effects.