Exploring the protective potential of berberine against cardiotoxicity and hepatorenal toxicity in rats

Cisplatin (CPN) is a platinum-based chemotherapeutic agent that exhibits therapeutic efficacy against several cancers; however, CPN induces multi-organ toxicity that is mediated by systemic oxidative stress and inflammation. Berberine (BRB) is an alkaloid-based polyphenolic compound with profound protective activities. This study aimed to investigate the impact of CPN or BRB on the heart-liver-kidney axis in CPN-intoxicated rats. Rats were given BRB orally, at protective doses of 50 and 100 mg/kg bodyweight/day for 14 days, interrupted by two intraperitoneal doses of CPN (7 mg/kg bodyweight) i.e., on the 7th day and the 14th day. Biochemical and histopathological investigations were conducted. CPN intoxication stimulated significant biochemical and histopathological alterations in the kidney, heart, and the liver. In contrast, BRB significantly mitigated CPN-induced elevations in serum levels of indices of kidney function, including kidney injury molecule-1 (KIM-1), myocardial function, and hepatic function, and reduced lipid peroxidation and nitric oxide production in the renal, cardiac, and hepatic tissues. However, BRB 100 demonstrated higher reductions in the levels of Brain natriuretic peptide (BNP) and Cardiac Troponin T (CTn-T). Histopathological findings showed that BRB reduced necrosis and inflammation and moderately alleviated structural alterations in CPN-intoxicated kidneys, heart, and liver. BRB, at both doses of 50 mg/kg and 100 mg/kg, reversed CPN-associated changes, however; BRB 100 exhibited a higher protective potential against CPN-induced multi-organ toxicity. Pending more comprehensive pharmacological and toxicological assessments, BRB may be regarded as a potential therapeutic adjuvant for mitigating pre-clinical CPN-induced biochemical and histopathological changes in a rodent model of CPN multi-organ toxicity.