Imipenem toxicity in male reproductive organs as a result of inflammatory microenvironment and oxidative stress in germinal cells.

ABSTRACT

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.