RENAL AND HEPATIC IMPAIRMENT BROUGHT ON BY CISPLATIN WITHOUT COMPROMISING ANTICANCER EFFICACY.

Abstract

One of the main disadvantages of cisplatin's therapeutic usage is that it can cause hepatic and renal dysfunctions. Part of its toxicity's chemical mechanism involves inducing inflammation. The effects of the selective JAK1-inhibitory anti-inflammatory drug upadacitinib on the side effects, histopathologic alterations, and kidney and in comparison, to silymarin and losartan, liver functions, oxidative stress, and inflammatory biomarkers were examined in male Wistar rats. In addition to receiving a single dosage of cisplatin (10 mg/kg) on the seventh day of treatment, the animals were given upadacitinib (10 mg/kg/day) for two weeks. Biochemical measurements were made of the oxidative biomarkers, inflammatory burst, liver, and kidney functioning, and more. Pretreatment with upadacitinib significantly improved liver function markers (ALT and AST) and prevented lipid profile abnormalities (triglycerides and total cholesterol) caused by cisplatin. Additionally, blood urea nitrogen, serum creatinine, creatinine clearance, and albumin levels all showed that it preserved kidney function. The lowering of MDA and TNFα levels suggests that upadacitinib also suppressed inflammatory processes produced by cisplatin in the liver and kidney.

Furthermore, it enhanced the activity of superoxide dismutase (SOD). Upadacitinib significantly reduced the structural damage caused by histopathology in the liver and kidney tissues. Upadacitinib's reno protective effects were verified by western blotting of NF-kB and p-Akt. Additionally, the assay for cell viability demonstrates that upadacitinib had no inhibitory effect on the anticancer efficacy of cisplatin in MCF-7 and A549 cells. Furthermore, cisplatin's effectiveness against lung cancer cells has been enhanced by upadacitinib in a dose-dependent manner. These findings demonstrate how upadacitinib can prevent cisplatin-induced toxicity without compromising its anticancer properties.

Keywords: Upadacitinib, Cisplatin, Anticancer properties, ALT, AST