Mitigating testicular dysfunction: Metformin's role in combating valproic acid-induced damage in rats

Area of Science:

• Reproductive toxicology
• Pharmacology
• Endocrinology

Background:

• Valproic acid (VPA), an anti-epileptic drug, is known to negatively impact male reproductive health.
• Testicular dysfunction is a significant concern associated with VPA treatment.

Purpose of the Study:

• To investigate the protective effects of metformin against VPA-induced testicular damage in a rat model.
• To evaluate metformin's impact on sperm parameters, hormone levels, oxidative stress, inflammation, and apoptosis.

Main Methods:

• Male Sprague-Dawley rats were divided into control, metformin, VPA, and VPA+metformin groups.
• Treatments were administered daily for 42 days.
• Evaluated parameters included sperm characteristics, hormone levels, oxidative stress markers (MDA, glutathione), inflammatory mediators (IL-1β, TNF-α, TGF-β), and apoptotic indicators (Caspase-3, PCNA).

Main Results:

• VPA exposure significantly reduced sperm count and motility, altered hormone levels (testosterone, FSH, LH), and induced oxidative stress (increased MDA, decreased glutathione).
• VPA also increased inflammatory markers and apoptotic indicators, while suppressing antioxidant pathways (Nrf2, HO-1, NQO1).
• Metformin co-administration reversed these VPA-induced detrimental effects, restoring testicular function and biochemical markers.

Conclusions:

• Metformin demonstrates significant protective effects against VPA-induced testicular toxicity in rats.
• Metformin enhances antioxidant defenses via the Nrf2/HO-1/NQO-1 pathway and suppresses inflammatory and apoptotic processes.
• Metformin represents a potential therapeutic agent to mitigate male reproductive side effects of VPA.