Ivermectin-mediated GABA _B receptor modulation ameliorates testicular torsion/detorsion-induced germ cell apoptosis and oxidative stress in rats

Testicular torsion, a medical condition contributing to male infertility, results in severe scrotal pain and ischemia. Oxidative stress factors contribute to germ cell death following surgical reperfusion, suggesting postoperative pharmacotherapy could mitigate testicular ischemia/reperfusion (I/R) injury. Ivermectin, a GABA receptor modulator for treating parasitic infections such as onchocerciasis, has demonstrated anti-oxidative stress and anti-apoptotic properties. Therefore, this study aimed to evaluate the efficacy of ivermectin administration after detorsion using a rat model of testicular torsion/detorsion (T/D). This study utilized 40 male Wistar rats weighing 200-250 grams. The studied groups were the sham (no T/D induction), control (T/D and no treatment), and T/D following administration of ivermectin administration and the doses of 1, 2, and 5 mg/kg intraperitoneally. For I/R surgery, both testes were twisted 720 degrees clockwise for 4 h to cause torsion. Subsequently, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were assessed using ELISA, while the expression of GABA_B receptors and apoptosis were examined using the immunohistochemical method. Histopathological alterations were evaluated with hematoxylin and eosin (H&E) staining to evaluate cell counts and seminiferous tubule diameters. Administration of ivermectin effectively reduced oxidative stress levels, as evidenced by decreased MDA levels and increased SOD activity, compared to the control group (P < 0.01 and P < 0.05, respectively). Ivermectin also modulated the expression of elevated GABA_B receptors and caspase 3 (P < 0.05 and P < 0.001, respectively). Furthermore, histopathological analysis revealed that ivermectin prevented germ cell degeneration, edema, and hemorrhage in the testis (P < 0.05). Ivermectin may be a potential treatment option for protecting against testicular torsion and may have beneficial effects on mitigating germ cell death, oxidative stress, and GABA_B receptor modulation. Further research is needed to explore dosages, long-term impacts, and clinical trials to determine the potential for patients with testicular torsion.