Modulatory effect of ciprofloxacin, a broad spectrum antibacterial drug, on mPT pore using rat model with estradiol benzoate-induced endometrial hyperplasia.

Abstract

Mitochondrial permeability transition (mPT) pore has become a motive for drug evolvement pertinent to dysregulated apoptosis situations. Some chemical compounds impede tumor/cancer via the inception of mPT pore opening. Ciprofloxacin has been demonstrated to hinder growth and effect apoptosis in some cancer cells. However, using a rat model, this study investigated its effect on mitochondrial-mediated cell death via mPT pore opening and estradiol benzoate (EB)-induced endometrial hyperplasia. Mitochondria were isolated using differential centrifugation. The opening of the pore, cytochrome c release (CCR), mitochondrial ATPase (mATPase) activity, mitochondrial lipid peroxidation (mLPO), caspases 3 and 9 levels, and hepatic DNA fragmentation were determined. Histological evaluation of hepatic and uterine sections and immunoexpression levels of Bax, caspase 3, and anti-apoptotic Bcl-2 levels were quantified. The results show that ciprofloxacin caused mPT pore opening, CCR, mATPase activity, effected mLPO, caspases 3 and 9 activations, and hepatic DNA fragmentation. The histology of the liver section showed moderate to marked disseminated congestion at 100 mg/kg, while higher doses showed severe hepatic damage. Severe EH was detected in the EB-treated rats which was attenuated by ciprofloxacin in the treatment group. The Bax and caspase expressions were upregulated by ciprofloxacin while anti-apoptotic Bcl-2 was downregulated. Ciprofloxacin induces mitochondrial-mediated cell death via mPT pore opening and mitigates EB-induced EH in rat models via Bax/caspase/Bcl-2 signaling pathway.