Cyclosporine A induces kidney dysfunction by the alteration of molecular mediators involved in slit diaphragm regulation and matrix metalloproteins: the mitigating effect of curcumin. (1st December 2020)

• Record Type: Journal Article
• Authors: Niazi, Mona; Shirpoor, Alireza; Taghizadeh Afshari, Ali; Naderi, Roya; Bagheri, Morteza; Pourjabali, Masoumeh; Rasmi, Yousef
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 16:Number 12(2020)
• Page Start: 1223
• Page End: 1231
• Publication Date: 2020-12-01
• Subjects: Cyclosporine-A -- podocyte -- slit diaphragm -- curcumin -- rat; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2020.1822323
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Background: This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. Methods: Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. Results: A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. Conclusion: Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.