Caesalpinia bonducella mitigates oxidative damage by paracetamol intoxication in the kidney and intestine via modulating pro/anti-inflammatory and apoptotic signaling: an In vivo mechanistic insight.

Abstract

Protracted use of paracetamol at therapeutic/toxic doses readily induces major organ toxicity and poor clinical efficacy. Caesalpinia bonducella seeds possess a diverse range of biological and therapeutic activities. Thus, our study aimed to scrutinize the toxic effects of paracetamol and the potential renal and intestinal protective effects of Caesalpinia bonducella seed extract (CBSE). To Wistar rats, CBSE was administered for 8days (300mg/kg, p.o.) with or without paracetamol (2000mg/kg, p.o.) on the 8th day. Pertinent toxicity assessments in the kidney and intestine were analyzed at the end of the study. The CBASE's phytochemical components were examined using gas chromatography-mass spectrometry (GC-MS). After the study period, study findings evidenced that paracetamol intoxication induced elevation of renal enzyme indicators, oxidative damage, imbalance with the pro/anti-inflammatory production and pro/anti-apoptotic mediators, and tissue injury; all repercussions were alleviated by pre-treatment with CBASE. CBASE considerably reduced (P < 0.05) paracetamol-induced kidney and intestine injury by limiting caspase-8/3 signaling and amplification of inflammation in renal and intestinal tissue by significantly reducing pro-inflammatory cytokine production. As per the GC-MS report, three main bioactive components-Piperine, Isocaryophyllene, and Tetradec-13-en-11-yn-1-ol were predominant and have protective activities. Our study ascertains that CBSE pre-treatment exerts potent renal and intestine protection against paracetamol intoxication. Thus, CBSE could be a prospective therapeutic candidate for protecting the kidney and intestine from the severity of paracetamol intoxication.