Chlorogenic acid abates oxido-inflammatory and apoptotic responses in the liver and kidney of Tamoxifen-Treated rats

Abstract

Plant-derived phenolics are utilized as chemopreventive agents to abate adverse toxic responses associated with drug-induced damages. Tamoxifen (TAM)-a chemotherapeutic agent-is used in managing all stages of hormone-dependent breast cancer. Notwithstanding TAM's clinical side effect-including hepatic toxicity-its use is commonplace. The present study investigates the effect of Chlorogenic acid (CGA: 25 and 50 mg kg-1; per os (p.o)) reported to exhibit various beneficial properties, including antioxidative effect against TAM (50 mg/kg; p.o.)-induced hepatorenal toxicities in rats treated as follows: Control, CGA, or TAM alone, and rats co-Treated with CGA and TAM for 2 weeks. Biomarkers of hepatorenal function, oxido-inflammatory stress, and hepatorenal histopathology were performed. We observed that TAM alone decreased relative organ weights (ROW), marginally impacted rat's survivability, and significantly (P < 0.05) increased hepatorenal toxicities and reactive oxygen and nitrogen species (RONS). TAM decreased (P < 0.05) antioxidant, anti-inflammatory cytokine (IL-10), besides increase in (P < 0.05) lipid peroxidation (LPO), pro-inflammatory cytokines (IL-1β, TNF-α), nitric oxide (NO), xanthine oxidase (XO), myeloperoxidase (MPO), and apoptotic caspases (Casp-3 and-9) levels. These biochemical alterations were accompanied by morphological lesions in experimental rats' liver and kidney. Conversely, that CGA dose-dependently relieved TAM-mediated toxic responses, restored antioxidants capacities, reduced oxidative stress, pro-inflammatory cytokines levels, and Casp-3 and-9 activities in experimental rats. Furthermore, CGA protected against lesions observed in the liver and kidney of rats treated with TAM alone. Overall, CGA blocked TAM-mediated hepatorenal injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. CGA may serve as a chemoprotective agent boosting patients prognosis undergoing TAM chemotherapy.