Tacrolimus induced nephrotoxicity and pulmonary toxicity in Wistar rats

Abstract

Transplantation has evolved into an accepted treatment for end-stage organ failure. The major limitation for solid organ transplantation is organ rejection, which is an adaptive immune response caused by the activation of T-cells. Immunosuppressant drugs are used to overcome this problem. Tacrolimus is a powerful immunosuppressive drug which is used to minimize the risk of organ rejection. The present study was designed to find the toxic effects of tacrolimus on lungs and kidneys. Wistar rats were divided into 4 experimental groups and one control group (n=9). Each rat of the experimental group was orally given the aqueous suspension of tacrolimus powder (3mg/ml) and dissected after 6, 12, 24 and 48 hours of tacrolimus suspension dose. Lungs and kidneys were excised and processed for histopathological and histochemical alterations. Kidney tissues presented signs of toxic potential on tissue architecture such as increased interstitial spaces, necrosis, especially acute tubular necrosis, glomerular shrinkage, dilated blood vessels and enlargement of Bowman’s capsule. Lung sections also confirmed the toxic potential, characterized by bronchiolar wall thickening, alveolar cells necrosis, collapsing of alveolar spaces and interstitial round cell infiltrate. Results of Prussian blue iron staining showed no iron deposition in kidney architecture while in lung sections, iron accumulation was evident. Taken together from these observations we can conclude that tacrolimus may induce toxicity to a certain extent with structural distortion of the kidneys and lungs