Cyclosporine A induces kidney dysfunction by the alteration of molecular mediators involved in slit diaphragm regulation and matrix metalloproteins: the mitigating effect of curcumin

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.

KEYWORDS:

• Cyclosporine-A
• podocyte
• slit diaphragm
• curcumin
• rat

Author contributions

M Niazi and A Shirpoor contributed to conception, design, data analyses, and drafting the manuscript, R Naderi and A T Afshari conceived and designed the experiments, M Bagheri. contributed to gene expression analysis, M Pourjabali contributed to pathological examination and analysis, Y Rasmi critically revised the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.