The ameliorative effects of chrysin on bortezomib-induced nephrotoxicity in rats: Reduces oxidative stress, endoplasmic reticulum stress, inflammation damage, apoptotic and autophagic death

Abstract

AimBortezomib is a proteasome inhibitor antineoplastic agent that was the first to be approved for cancer treatment. One of bortezomib's most prominent dose-limiting effects is nephrotoxicity; the underlying mechanism is believed to be oxidative stress. Chrysin is a compound found actively in honey and many plant species and stands out with its antioxidant properties. The present study aimed to determine the ameliorative effects of chrysin in bortezomib-induced nephrotoxicity. Material-methodThirty-five male Wistar rats were divided into control, BTZ, CHR, BTZ + CHR25, and BTZ + CHR50. Biochemical, molecular, Western blot, and histological methods analyzed renal function indicators, oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and damage pathways. ResultsChrysin decreased oxidative stress by reducing oxidants (MDA) and increasing antioxidants (SOD, CAT, Gpx, GSH, Nrf-2, HO-1, NQO1). Chrysin reduced endoplasmic reticulum stress by decreasing ATF-6, PERK, IRE1, and GRP-78 levels. Chrysin reduced inflammation damage by inhibiting the NF-κB pathway. Chrysin exhibited protective properties against apoptotic damage by decreasing Bax and Caspase-3 levels and increasing Bcl-2 levels. In addition, chrysin improved renal function and structural integrity and exhibited healing properties against toxic damage in tissue structure. ConclusionOverall, chrysin exhibited an ameliorative effect against bortezomib-induced nephrotoxicity.