Octreotide ameliorates Bisphenol A-induced testicular toxicity via autophagy-inflammation pathway modulation

IntroductionTesticular toxicity commonly manifests as impaired spermatogenesis and testicular atrophy. Bisphenol A (BPA), a commonly used organic plasticizer, negatively affects sperm parameters, hormonal levels, and fertility. Octreotide (OCT), a somatostatin analog, was originally used to treat acromegaly, carcinoid tumors, vasoactive intestinal peptide-secreting, and growth hormone-secreting tumors. OCT has demonstrated potential therapeutic properties beyond its traditional use in endocrine disorders. We hypothesized that OCT would attenuate BPA-induced testicular damage through its anti-inflammatory, anti-oxidant, and anti-autophagic properties. This study aimed to assess the mechanisms of BPA-induced testicular toxicity and evaluate the ameliorative effects of OCT.MethodsForty adult male Sprague Dawley (SD) rats were randomly assigned to four equal groups: group1: saline control, group2: dimethyl sulfoxide (DMSO) vehicle, group3: BPA-treated, and group4: BPA + OCT-treated. Treatments were administered for 4 weeks. Sperm count, testicular weight, serum testosterone, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total antioxidant capacity (TAC), testicular levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα), Beclin-1 (BECN-1), Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A/LC3), mammalian target of rapamycin (M-TOR), histopathological examination, apoptotic index, and Johnson's score were assessed.ResultsBPA administration significantly impaired spermatogenesis, reduced serum testosterone and TAC, and increased MDA, TNFα, and autophagy-related markers, along with histopathological damage of testis. Co-treatment with OCT mitigated these effects by improving sperm parameters, hormone levels, oxidative stress markers, inflammatory cytokines, and testicular histology.DiscussionThe findings suggest that OCT exerts a protective effect against BPA-induced testicular toxicity, through its anti-inflammatory, antioxidant, and autophagy-modulating properties. OCT may offer therapeutic potential in mitigating BPA-induced testicular toxicity.