Safety assessment of cefuroxime on male reproductive system: Subacute toxicity and potential reversibility after a complete cycle of spermatogenesis and epididymal maturation in Wistar rats.

The effects of cefuroxime on reproductive system were investigated in male rats. Doses of 0, 30, 60 or 120 mg/kg of cefuroxime were intraperitoneally injected daily, for 7 days. Half of the rats were euthanized 24 h after the last dose and other half were induced to death 70 days after the last treatment. After 8 days of the experiment, results showed that cefuroxime induced a significant reduction in the weights of testes, epididymis and accessory sex organs. In addition, it decreased sperm quality, plasma testosterone level, and antioxidant enzyme activities while increasing the level of malondialdehyde. After a complete cycle of spermatogenesis and epididymal maturation, the results indicated complete reversibility of the adverse effects previously mentioned. In conclusion, cefuroxime induced reversible dose-dependent adverse effects on testicular and epididymal functions of rats.

Exposure to imipenem/cilastatin causes nephrotoxicity and even urolithiasis in Wistar rats.

Imipenem/cilastatin is a broad-spectrum ß-lactam antibiotic used to treat several bacterial infections. The present study was designed to validate the nephrotoxic effect of this drug in rats and to explore its potentional urolithiatic effect. Thirty two Wistar rats were randomly divided into four groups: three experimental groups treated with different imipenem/cilastatin dosages (30, 50 and 80 mg/kg/day) and a control group.The experimental groups were given intraperitoneal imipenem/cilastatin injections twice daily for 7 days, and the control group was given intraperitoneal vehicle NaCl 0.9% solution. Nephrotoxic effect of this antibiotic was assessed based on urine and plasma biochemistry, oxidative stress parameters, histopathological examination and infrared spectroscopy characterization. Imipenem/cilastatin administration resulted in alkaline urine, polyuria, crystalluria, raised plasma levels of urea, creatinine and uric acid, decreased contents of plasma gamma glutamyltranspeptidase and alkaline phosphatase, oxidative stress status, malpighian metaplasia as well as crystal deposition in kidneys and urinary tracts of Wistar rats. In addition, the precise nature of the calculi was identified, being formed by imipenem/cilastatin, thus confirming their iatrogenic origin. In conclusion, this study demonstrated through rat model that subacute exposure to imipenem/cilastatin may induce nephrotoxicity and increase the risk for developing kidney stones even at therapeutic dose levels in a dose-dependent manner.

A carbapenem antibiotic imipenem/cilastatin induces an oxidative stress-status and gonadotoxic effects in « wistar ¼ rats.

Imipenem is a carbapenem antibiotic largely used to treat infection diseases. The present study was designed to investigate the effects of imipenem/cilastatin (IMP) on oxidative stress, antioxidant levels, testicular structure and sperm parameters in rats. Adult Wistar rats (84days old; N=8/group) were treated intraperitoneally with physiological serum containing 0mg/kg, 30mg/kg, 50mg/kg and 80mg/kg of IMP for one week. The results revealed that exposure to IMP especially at high doses, significantly decreased sexual organs weights (testis, epididymis, seminal vesicle and prostate), sperm characteristics (motility, viability and count) and plasma testosterone level while increased sperm abnormality. In addition, the testicular tissue level of lipid peroxidation (LPO) was significantly increased while the level of activities of superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GPx) decreased compared to the control group. Severe testicular lesions were recorded in the seminiferous tubules as well as a significant impairment in sperm characteristics. In conclusion, IMP induced an oxidative stress-status and histopathological changes in the testis and altered spermatogenesis in particular at both 50 and 80mg/kg dose-levels (p<0.001).