Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, B.P. 1177, 3018 Sfax, Tunisia.
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, B.P. 1177, 3018 Sfax, Tunisia; Department of Anatomopathology, CHU Habib Bourguiba, Sfax, Tunisia.
Toxicology. 2019 Mar 15;416:44-53. doi: 10.1016/j.tox.2019.02.001. Epub 2019 Feb 2.
Imipenem is a beta-Lactam antibiotic characterized by a broad spectrum of activity. It is prescribed to treat severe infections. Our goal is to investigate toxicity induced in male rat reproductive systems following exposure to this drug (15, 50 or 100 mg/kg) compared to gentamicin (50 mg/kg) treatment. Effects of imipenem on reproductive organ weights, histoarchitecture, sperm parameters, and oxidative stress parameters were evaluated. Serum testosterone levels were measured. Apoptosis and inflammatory behaviors were investigated by immunohistochemical proteins expression analysis of apoptosis regulator BAX (Bax), B-cell lymphoma 2 (Bcl-2), and interleukin-1 beta (IL-1 beta) in testis. Results showed a significant decrease in male fertility parameters including sperm count, sperm motility, reproductive organ weights and serum testosterone levels after imipenem administration as compared to the control and gentamicin treated groups. Increased sperm abnormality was significant in animals treated with high doses of imipenem. Oxidative stress analysis revealed an expressed increase in lipid peroxidation and carbonyl groups levels in testicular tissues compared to control. Similar results were observed with superoxide dismutase and catalase activities from testicular tissues. In addition, severe testicular lesions were observed in the seminiferous tubules as well as important impairments in spermatogenesis testifying an inflammatory microenvironment confirmed by the intensive expression of IL1-beta and Bax protein by germinal cells and Bcl-2 by Leydig cells. In conclusion, imipenem treatment with high doses was found to lead to oxidative stress in male reproductive organs and an inflammatory microenvironment leading to spermatogenesis dysfunction and histopathological changes in the testis.
亚胺培南是一种具有广谱活性的β-内酰胺抗生素。它被开处方用于治疗严重感染。我们的目标是研究与庆大霉素（50mg/kg）治疗相比，这种药物（15、50 或 100mg/kg）暴露后对雄性大鼠生殖系统引起的毒性。评估了亚胺培南对生殖器官重量、组织形态结构、精子参数和氧化应激参数的影响。测量了血清睾酮水平。通过对睾丸中凋亡调节因子 BAX（Bax）、B 细胞淋巴瘤 2（Bcl-2）和白细胞介素 1β（IL-1β）的免疫组织化学蛋白表达分析，研究了亚胺培南对凋亡和炎症行为的影响。结果表明，与对照组和庆大霉素治疗组相比，雄性生育参数包括精子计数、精子活力、生殖器官重量和血清睾酮水平在亚胺培南给药后显著降低。高剂量亚胺培南处理的动物精子异常明显增加。与对照组相比，睾丸组织中的脂质过氧化和羰基水平的氧化应激分析显示表达增加。睾丸组织中超氧化物歧化酶和过氧化氢酶活性也观察到类似结果。此外，在曲细精管中观察到严重的睾丸损伤，以及生精作用的重要损害，证明了炎症微环境，这通过生殖细胞中 IL1-β和 Bax 蛋白以及 Leydig 细胞中 Bcl-2 的强烈表达得到证实。总之，高剂量的亚胺培南治疗被发现会导致雄性生殖器官的氧化应激和炎症微环境，导致生精功能障碍和睾丸组织学变化。
