The synthetic cannabinoid JWH-018 induces testicular oxidative stress and alters nitric oxide synthase expression in mice

Abstract

Thirty adult male CD-1 mice were randomly assigned to six groups (n = 5 each): two control groups (C1, C2), two ethanol vehicle groups (E1, E2), and two JWH-018–treated groups (JWH1, JWH2). Control groups received saline, ethanol groups received 1% ethanol in saline (vehicle), and JWH groups received JWH-018 (0.3 mg/kg, i.p.) once daily for nine days. Acute effects were assessed in C1, E1, and JWH1 animals sacrificed two days post-treatment, while recovery potential was evaluated in C2, E2, and JWH2 animals sacrificed 45 days later. JWH-018 exposure caused significant reductions in seminiferous tubule diameter and CSA, with germinal epithelium thickness preserved. Morphological damage was partially reversed in the recovery group (JWH2). Immunohistochemical analysis revealed increased iNOS and eNOS expression, particularly in Leydig cells, indicating oxidative stress, while PAS staining revealed apoptotic-like germ cells in JWH groups. Our findings indicate that JWH-018 induces testicular injury through oxidative stress–mediated pathways, causing structural and cellular alterations. Partial recovery was observed after a full spermatogenic cycle; however, some changes persisted, suggesting potential long-term reproductive consequences. These results provide novel insights into the mechanisms of JWH-018–induced reproductive toxicity and underscore the importance of further investigation into potential interventions.

Keywords

• JWH-018
• synthetic cannabinoids
• testis
• oxidative stress
• iNOS
• eNOS.

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