Acetaminophen (APAP) is a widely consumed analgesic-antipyretic drug found in several nonprescription pharmaceutical compounds such as Panadol. It is globally recommended as a first-line agent for the treatment of fever and pain due to its few contraindications. APAP lacks the significant gastrointestinal and cardiovascular side effects associated with nonsteroidal anti-inflammatory drugs. The easy accessibility and low price of this drug masks the potential danger of its misuse with subsequent occurrence of acute, subacute or chronic toxicity. Hepatic and renal damage are well-recognized complications of APAP poisoning, but other vital organs toxicity are neither studied nor described well in the literature. Also, the effects of its chronic administration on male reproductive system functions remain largely unknown. So, the present study was designated to explore the effect of short-term APAP administration on adult albino rats' testes. The study was conducted on 20 adult male albino rats, divided equally into 2 groups. Group I (control group): each fasted rat received 2 ml of normal saline. Group II (APAP group): each fasted rat received 500 mg/kg of APAP dissolved in 2 ml of normal saline. Each group received their corresponding substance daily via intragastric tube for 60 consecutive days then sacrificed. The separated serum samples were used for estimation of testosterone, luteinizing hormone, and follicle stimulating hormone levels. The dissected epididymides were analyzed for different sperm quality parameters (count, motility, and normal morphology). Also, the removed testes were prepared for histopathological and ultrastructural examination. The hormonal assay results depicted significant reduction in testosterone along with significant elevation in luteinizing hormone and follicle stimulating hormone levels. There were also significant reduction in both testicular and epididymides weights as well as significant depletion in all analyzed sperm quality parameters. Testicular specimens from treated rats showed variable histological and ultrastructural degenerative changes in germ cells and Sertoli cells in many seminiferous tubules as well as Leydig cells and blood vessels. Disturbance of the regular arrangement of the spermatogenic cell layers in the testis were also observed. So, much more attention should be paid to this drug as a possible source of adult male reproductive organs toxicity with decreasing fertility especially when chronically ingested for a long period by humans. On the other hand, this drug may carry the potential of inducing damage to the testes during their development that lead to primary hypogonadism if given repeatedly for long time to male children. Thus, APAP should be used cautiously by males on a chronic prolonged basis because of its orchidotoxic effect that may diminish fertility.
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