Protective effects of coenzyme Q10 against trihexyphenidyl-induced testicular oxidative damage: modulation of antioxidant enzymes, inflammatory markers, hormonal and steroidogenic pathways in rats

Abstract

Background: Trihexyphenidyl is clinically effective for Parkinson's disease and antipsychotic-induced extrapyramidal symptoms. However, its abuse potential and adverse effects on male reproductive health are significant concerns. Coenzyme Q10 (CoQ10), a potent antioxidant, is known to protect reproductive tissues from injury. This study investigated the protective effects of CoQ10 against trihexyphenidyl-induced testicular damage in male Wistar rats.

Methods: Twenty male Wistar rats (160-180 g) were randomly allocated into four groups (n = 5/group): control (Tween 80), trihexyphenidyl (1.5 mg/kg), CoQ10 (10 mg/kg), and trihexyphenidyl + CoQ10. Treatments were administered orally for 60 days. Testicular tissue biomarkers and serum hormone levels were analyzed.

Results: Trihexyphenidyl treatment significantly reduced relative paired epididymal and testicular weights, along with serum levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone, and Testosterone. It also decreased the activity of steroidogenic enzymes (3β-HSD, 17β-HSD) and antioxidant enzymes (SOD, GPx, Catalase) compared to controls. Conversely, trihexyphenidyl increased markers of oxidative stress (MDA, 8-OHdG), inflammation (TNF-α, MPO, IL-1β), apoptosis (caspase-3), and altered lactate/pyruvate levels, accompanied by significant histopathological damage. Co-administration of CoQ10 with trihexyphenidyl significantly attenuated these detrimental effects, restoring biochemical parameters and improving testicular architecture.

Conclusion: Coenzyme Q10 effectively protects against trihexyphenidyl-induced testicular toxicity by mitigating oxidative stress, inflammation, and apoptosis, while preserving steroidogenic enzyme activity and hormonal balance. These findings highlight CoQ10's potential as a therapeutic agent to counteract the reproductive side effects of trihexyphenidyl.

Keywords: Coenzyme Q10; Enzymes; Epididymis; Inflammation; Oxidative stress; Testes; Trihexyphenidyl.