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Nephrotoxicity Induced by Cisplatin Intake in Experimental Rats and Therapeutic Approach of Using Mesenchymal Stem Cells and Spironolactone

Elseweidy, MohamedM., Askar, MervatE., Elswefy, SaharE., Shawky, Mohamed
Applied biochemistry and biotechnology 2018 v.184 no.4 pp. 1390-1403
antagonists, anti-inflammatory activity, anti-inflammatory agents, biomarkers, body weight, chemokines, cisplatin, creatinine, extracellular matrix, fibroblasts, fibrosis, glutathione, hepatocyte growth factor, histopathology, insulin-like growth factor I, intravenous injection, kidney diseases, kidneys, malondialdehyde, mineralocorticoid receptors, nephrotoxicity, rats, spironolactone, stem cells, transcription factor NF-kappa B, urea
Chronic kidney disease may lead to subsequent tissue fibrosis. However, many factors can combat injurious stimuli in these tissues aiming to repair, heal, and alleviate any disturbance. Chemokines release, migration of inflammatory cells to the affected site, and activation of fibroblasts for the production of extracellular matrix are commonly observed in this disease. In the last years, many studies have focused on spironolactone (SPL), a mineralocorticoid receptor antagonist, and its pharmacological effects. In the present study, SPL was selected as an anti-inflammatory agent to combat nephrotoxicity and renal fibrosis induced by cisplatin. Mesenchymal stem cells (MSCs) were also selected in addition as a referring agent. Renal fibrosis induced by cisplatin intake significantly increased creatinine, urea, nuclear factor kappa B, insulin-like growth factor-1, fibroblast growth factor-23, and kidney malondialdehyde (MDA) content. Hepatocyte growth factor and renal content of reduced glutathione demonstrated a significant decrease. Histopathological examination of kidney tissues demonstrated marked cellular changes which are correlated with the biochemical results. Oral SPL intake (20 mg/kg/body weight) daily for 4 weeks and MSCs administration (3 × 10⁶ cell/rat) intravenous to the experimental rats resulted in a significant improvement of both the biomarkers studied and the histopathological profile of the renal tissue. Individual administration of spironolactone and MSCs exhibited a marked anti-inflammatory potential and alleviated to a great extent the nephrotoxicity and renal fibrotic pattern induced by cisplatin.