Zinc mitigates hormonal disturbance associated with acetaminophen-induced testicular dysfunction in rat

Abstract

Background: Acetaminophen (ACP) is one of the most commonly used over-the-counter analgesic drug; and thus frequently subject to misuse and abuse. Several studies have reported various deleterious effects of acetaminophen overdose or long term administration.

Objective: This study was designed to determine if zinc (Zn) will protect against or mitigate acetaminopheninduced impairment of testicular function.

Methods: Twenty five Sprague-Dawley rats were randomly divided into five groups (n=5/group): Group I (control) received 1mL of normal saline; Group II received 1000mg/Kg BW of ACP only; Group III received 10mg/Kg BW of Zn only, Group IV were co-administered with ACP (1000mg/Kg) and Zn (10mg/Kg) and Group V were posttreated with Zn (10mg/Kg) after ACP (1000mg/Kg) administration. Following 14 days of consecutive administration, except in group V that were post-treated for additional 14 days, rats were euthanized by cervical dislocation to obtain blood sample through cardiac puncture for hormonal assays. Testes and epididymides were quickly recovered for daily sperm production (DSP) and semen analysis.

Results: There was no significant difference in DSP in all treated groups compared with control. Sperm concentration and progressive motility were significantly reduced in ACP group compared with control and groups treated with Zn. Significant increase in head, neck and tail defects was observed in ACP compared with control and groups treated with Zn. There were no significant differences in the concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) between control and any of the treated groups. However, testosterone (T), estradiol (E₂) and Zn levels were significantly lower in acetaminophen-treated rats which were reversed with Zn administration.

Conclusion: The deleterious effect of ACP appears not to be mediated through gonadotropin suppression but rather by either decreased sensitivity or suppressed steroidogenesis secondary to Zn depletion. However, treatment with Zn protects the testis against acetaminophen-induced testicular dysfunction.

Keywords: Acetaminophen, Zinc, Sperm Morphology, Sperm Motility, hormone