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. 2022 Apr;395(4):387-395.
doi: 10.1007/s00210-022-02212-8. Epub 2022 Jan 29.

Ferulic acid prevents cyclosporine-induced nephrotoxicity in rats through exerting anti-oxidant and anti-inflammatory effects via activation of Nrf2/HO-1 signaling and suppression of NF-κB/TNF-α axis

Ali Nouri  1 , Keihan Ghatreh-Samani  2 , Hossein Amini-Khoei  3 , Asghar Mohammadi  1 , Esfandiar Heidarian #  4 , Mohammad Najafi #  5
Affiliations

Ferulic acid prevents cyclosporine-induced nephrotoxicity in rats through exerting anti-oxidant and anti-inflammatory effects via activation of Nrf2/HO-1 signaling and suppression of NF-κB/TNF-α axis

Ali Nouri et al. Naunyn Schmiedebergs Arch Pharmacol. 2022 Apr.

Abstract

Cyclosporine is one of the main immunosuppressive agents used in the treatment of autoimmune diseases or transplantation. Despite the favorable effects, cyclosporine-mediated nephrotoxicity critically restricts the clinical use of the agent. Given this, herein, we aimed to evaluate whether ferulic acid could prevent cyclosporine-mediated nephrotoxicity in rats. A total of 32 Wistar rats were chosen to be treated with cyclosporine, ferulic acid, and the combination of both agents for 21 days. To evaluate the nephron-protective mechanism of ferulic acid, the serum levels of biochemical parameters, as well as the tissue levels of several oxidative and anti-oxidative mediators, were examined. The expression and the tissue levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, heme oxygenase (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2) were evaluated using the qRT-PCR and ELISA, respectively. Our results showed while cyclosporine elevated the serum levels of renal-related markers in the rats, in the presence of ferulic acid, there was a significant reduction in the levels of urea, uric acid, creatinine, and sGOT. Moreover, we found that ferulic acid remarkably prevented cyclosporine-mediated nephrotoxicity by restoring the anti-oxidant system through activating the Nrf2/HO-1 axis. By halting the NF-κB-mediated upregulation of TNF-α, it also seems that ferulic acid prevented lymphocytes infiltration into kidney tissue and consequently suppressed inflammatory responses. Overall, the results of the present study suggest that due to the anti-oxidant and anti-inflammatory properties of ferulic acid, this agent could be used alongside cyclosporine to reduce its adverse effects on kidney tissue.

Keywords: Anti-inflammatory responses; Anti-oxidant system; Cyclosporine; Ferulic acid; Nephrotoxicity.

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