possible protective role of lisinopril as a pro-apoptotic agent in cyclosporin A induced nephrotoxicity in rats

ABSTRACT

The study was carried out on 40 male albino rats, which were divided into five groups Group 1, normal control group, group 2, saline treated group, group 3, cyclosporin A treated group [rats received saline 0.2 ml for one week orally daily, then received cyclosporin A [20 mg/kg/day] intraperitoneally daily for another week], group 4, lisinopril plus cyclosporin A treated group [treatment with lisinopril [10 mg/kg/day] orally for one week, then co-administration, of both lisinopril and cyclosporin A for another one week using the aforementioned doses] and group 5, lisinopril-treated group [rats received lisinopril [10 mg/kg/day] orally for two weeks]. At the end of the study, blood samples were withdrawn from rats of all groups for determination of serum creatinine. Afterwards, rats were sacrificed and the kidneys were obtained. Sections from the kidney were stained by hematoxylin and oesin and immunohistochemically using anti-Bcl-2 antibodies for assessment of both necrosis and apoptosis, respectively. Cyclosporin A administration for one week significantly raised the serum creatinine level. Also, it produced histopathological changes confined to the proximal convoluted tubules in the form of moderate to severe focal necrosis, and produced strong Bcl-2 cytoplasm immunostaining. Treatment with lisinopril for one week, then co-administration, of both lisinopril and cyclosporin A, decreased significantly the cyclosporin A-induced elevation of serum creatinine, decreased the focal necrosis in the proximal convoluted tubules [Chi square=13.3], and produced weak Bcl-2 cytoplasm immunostaining [Chi square=7.27]. This denotes that the ACE inhibitor ameliorated the toxic insult induced by CsA by favoring induction of apoptosis as denoted by diminishing the Rcl-2 cytoplasmnostaining. From the above data, it could be concluded that lisinopril has a proapoptotic effect in the kidney after cyclosporin A-induced nephrotoxicity