Acyclovir induces testicular damage and impairs HPT axis by upregulating oxidative enzymes and inflammatory cytokines in male Wistar rats.

Objective: Acyclovir is an antiviral drug that is used to treat herpes virus infections and acts by inhibiting viral DNA synthesis. While antiviral drugs are designed to inhibit viral replication, some have been found to have immunomodulatory effects beyond their direct antiviral action. Acyclovir has been documented to induce cytotoxicity and DNA mutation. Cytotoxic agents are well-documented to damage male gonadal functions. Therefore, it has become imperative to examine the effects of acyclovir on male reproductive physiology.

Methods: Eighteen adult male Wistar rats were randomly grouped into three groups: control (distilled water), low-dose (10 mg/kg acyclovir), and high-dose (40 mg/kg acyclovir). After 21 days of oral treatment, serum, testicular homogenate, and epididymal sperm suspension were collected and analyzed. Serum and testicular oxidative stress markers (SOD, MDA, GPx, and CAT), hypothalamic-pituitary-gonadal hormones (GnRH, LH, FSH, and testosterone), sperm parameters, and testicular histoarchitecture were examined. In addition, inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) and lactate dehydrogenase enzymes were evaluated from the serum.

Results: Acyclovir (40 mg/kg) caused a significant increase in serum inflammatory cytokines (TNF-α, IL-6), LDH, and MDA, while the testicular and serum antioxidant enzymes were reduced when compared with controls. Acyclovir (40 mg/kg) also decreased serum GnRH, LH, FSH, and testosterone levels, as well as testicular testosterone, and negatively affected sperm count, sperm motility, and sperm morphology. Histopathological examination showed that acyclovir caused edematous seminiferous tubules with degenerated spermatogenic cells and scanty sperm cells.

Conclusions: Acyclovir induced testicular damage by promoting inflammatory response, oxidative damage, and endocrine disruption.