Kinetin Ameliorates Cisplatin-Induced Hepatotoxicity and Lymphotoxicity via Attenuating Oxidative Damage, Cell Apoptosis and Inflammation in Rats

Biomedicines. 2022 Jul 6;10(7):1620. doi: 10.3390/biomedicines10071620.

Abstract

Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced liver and lymphocyte toxicity in rats. Wistar male albino rats were divided into nine groups: (i) the control (C), (ii) groups 2,3 and 4, which received 0.25, 0.5 and 1 mg/kg kinetin for 10 days; (iii) the cisplatin (cp) group, which received a single intraperitoneal injection of CP (7.0 mg/kg); and (iv) groups 6, 7, 8 and 9, which received, for 10 days, 0.25, 0.5 and 1 mg/kg kinetin or 200 mg/kg vitamin C, respectively, and Cp on the fourth day. CP-injected rats showed a significant impairment in biochemical, oxidative stress and inflammatory parameters in hepatic tissue and lymphocytes. PCR showed a profound increase in caspase-3, and a significant decline in AKT gene expression. Intriguingly, Kn treatment restored the biochemical, redox status and inflammatory parameters. Hepatic AKT and caspase-3 expression as well as CD95 levels in lymphocytes were also restored. In conclusion, Kn mitigated oxidative imbalance, inflammation and apoptosis in CP-induced liver and lymphocyte toxicity; therefore, it can be considered as a promising therapy.

Keywords: AKT; CD95; caspase-3; cisplatin; hepatotoxicity; lymphotoxicity; oxidative stress.

Grants and funding

E.M.O acknowledge the support of Büro der Universitätsfrauenbeauftragten University of Würzburg, Germany with the SCIENTIA grant-, TD thanks Land Bavaria for support (contribution to DFG Project number 324392634-TRR 221/INF) and M.N was supported by the Cluster Grant R20141 from Zayed University, AUE. This publication was supported by the Open Access Publication Fund of the University of Wuerzburg.