Iristectorin A Ameliorates Cisplatin‐Induced Hepatorenal Injury in Mice Through Modulation of the Nrf2/HO‐1 Signaling Pathway

Cisplatin (CIS) is a chemotherapeutic agent frequently used in cancer treatment. However, depending on the dosage and duration of use, CIS can lead to hepatotoxicity and nephrotoxicity. Iristectorin A (IRIS), a natural flavonoid, has been found to exhibit antioxidant and protective effects. In this paper, we scrutinized the effects and molecular mechanisms of the IRIS on CIS-induced liver and kidney damage in mice. IRIS administration alleviated CIS-induced elevations in AST, ALT, ALP, BUN, and creatinine levels by approximately 12%, 15%, 11%, 21%, and 15%, respectively. It also inhibited liver and kidney MDA levels by approximately 29% and 28%, while enhancing liver and kidney GSH, SOD, and CAT levels by 47%-60%, 85%-70%, and 90%-55%, respectively. IRIS enhanced liver and kidney mRNA expression levels of Nrf2 (by approximately 1.6- and 1.5-fold, respectively), HO-1 (by 1.5- and 1.5-fold, respectively), and Bcl-2 (by 1.5- and 1.4-fold, respectively). In addition, IRIS suppressed the mRNA expression levels of NF-κB (by 0.7- and 0.7-fold), TNF-α (by 0.7- and 0.7-fold), Bax (by 0.8- and 0.7-fold), and Cas-3 (by 0.9- and 0.7-fold). Protein expression analysis revealed that IRIS increased Nrf2 (by 1.5- to 1.2-fold) and Bcl-2 levels (by 1.3- to 1.7-fold), and reduced Bax (by 0.7- to 0.8-fold) and Cas-3 (by 0.8- and 0.8-fold) levels altered by CIS treatment. Moreover, IRIS administration prevented histopathological changes in the liver and kidney caused by CIS. Ultimately, IRIS was found to substantially mitigate CIS-induced hepatorenal injury by targeting oxidative stress, inflammation, and apoptosis through regulation of the Nrf2/HO-1 signaling pathway. Therefore, IRIS holds potential as a therapeutic adjuvant in the use of CIS.