Rutin inhibits carfilzomib-induced oxidative stress and inflammation via the NOS-mediated NF-κB signaling pathway

BackgroundCarfilzomib (CFZ), a proteasome inhibitor approved by the FDA to treat multiple myeloma, may cause nephrotoxicity.HypothesisRutin is a bioflavonoid with antioxidant properties. We aimed to examine whether rutin protects the kidney from CFZ-induced nephrotoxicity.Study designThis study aimed to demonstrate the effect of rutin on CFZ-induced renal injury via the inhibition of oxidative stress and inflammation.MethodsWistar albino rats were divided into six groups (n=6): Group 1 (normal control; NC) was administered normal saline for 3weeks; Group 2 (CFZ/toxic group) received CFZ [4mg/kg, intraperitoneal (i.p.) injection] twice weekly for 3weeks; Group 3 (standard treatment group) was administered CFZ (4mg/kg, i.p.) and olmesartan (2mg/kg, p.o.) for 3weeks; Group 4 was administered CFZ (4mg/kg, i.p.) and rutin (10mg/kg, p.o.) for 3weeks; Group 5 was administered CFZ (4mg/kg, i.p.) and rutin (20mg/kg, p.o.) for 3weeks; and Group 6 was administered CFZ (4mg/kg, i.p.) and rutin (40mg/kg, p.o.) for 3weeks. We carried out haematological and biochemical analyses, determined oxidative stress, caspase-3 activity, and protein levels, and performed a histopathological evaluation to confirm CFZ-induced nephrotoxicity and its prevention by rutin administration.ResultsExposure to only CFZ significantly (p<0.05) increased white blood cell (WBC) count, Hb%, and HTC% concentration; however, these features were significantly decreased (p<0.05) when olmesartan and rutin were administered. CFZ administration significantly decreased (p<0.0001) the level of antioxidant enzymes; whereas, administration of olmesartan and rutin significantly reversed (p<0.05) their levels toward the normal range. The levels of caspase-3 enzyme significantly increased (p<0.001) in the CFZ group and were reduced toward the normal values by olmesartan and rutin administration. Furthermore, the results of NOS-2, NF-kappa B, IkBa, and IL-17 protein estimation and the histopathological evaluation strengthened our findings that rutin exhibits a protective effect against CFZ-induced nephrotoxicity.ConclusionThese findings clearly demonstrate that rutin ameliorates CFZ-induced oxidative stress and inflammation in nephrotoxicity via the NOS-mediated NF-kappa B signaling pathway.