Restorative effects of azadirachta indica on cisplatin induced nephrotoxicity in wister albino rats

Abstract

Cisplatin is a cytotoxic drug commonly used worldwide in the treatment of cancer. Despite its effectiveness, studies have shown that it can cause nephrotoxicity in 20-30% of the population that use it, as a result, its administration is restricted. Few studies have been done to elucidate the restorative effects of Azadirachta indica in human patients experiencing nephrotoxicity secondary to cisplatin usage. In addition, there is paucity of data on the restorative effects of azadirachta indica on cisplatin induced nephrotoxicity. The broad objective of this study was to determine the restorative effects of azadirachta indica on cisplatin induced nephrotoxicity in Wister albino rats. The specific objectives were to evaluate the histo- architectural and histo stereological restorative effect of azadirachta indica on cisplatin induce nephrotoxicity at varied dosage, to determine the gross histo-morphological changes on cisplatin induced nephrotoxicity, to determine the restorative effect of azadirachta indica on cisplatin induced nephrotoxicity by assessing the renal biomarkers of acute kidney injury. The study used a posttest-only experimental design. Adult albino rats were bred under microbiologically controlled conditions for all the experiments and control groups. A modified human resource equation was used to determine the sample size, A total number of 25 adult Wister albino rats were selected randomly and used in the study. The 25 albino rats were randomly assigned into two main groups of 5 control and 20 experimental. The 20 experimental Wister albino rats were further assigned into four experimental subgroups of 5 each and received water, rats’ pellets ad libitum, Azadiracta indica and cisplatin according to the experimental design below. The control group was not administered with any drug, received only water and rat pellets ad libitum. The group one from the experimental were only administered with cisplatin 0.28mg/kg at the beginning of the experiment. Group two, three and four were administered with cisplatin 0.28mg/kg at day one followed by low dose of 3.33mg/kg, medium dose 5.0mg/kg and high dose 6.67ml/kg of Azadirachta indica respectively at day five of the experiment, all animals were humanely sacrificed on day thirteen. The kidney tissues were prepared, stained using H & E and examined under 100X magnification using BP Olympus microscope. The photomicrographs were taken, uploaded and stored on a flash disk, Data were entered into the excel sheet and were analyzed using the SPPS version 27. There was a significance (P< 0.0001) increase in Urea & creatinine levels of the experimental GP1, 2 and 4 as compared to the control. There was significant (P ≤ 0.001, 0.001 and 0.003 respectively) reduction in mean body weight of experimental GP1, 2, and 4. There was significant (P < 0.0001**) reduction in the mean length, width, volume, thickness and weight of the kidney for experimental group as correlated with the control group. The surface area of the glomerulus of experimental GP1, GP2 and GP4 had a significant (P <0.0001**) reduction. The medium dose of Azadiracta indica of 5mg/kg was able to restore cisplatin-induced nephrotoxicity among the Wister albino rats. There was a significance increase in the surface area of the bowman’s capsule, glomerulus space and reduction in glomerulus in cisplatin-induced nephrotoxicity among the Wister albino rats.