Mohammed-Rashid Shayan Shwan, Dyary Hiewa Othman
Department of Basic Sciences, College of Veterinary Medicine, University of Sulaimani, New Sulaimani, Street 27, Sulaymaniyah 46001, Kurdistan Region, Iraq.
J Toxicol. 2025 Sep 3;2025:6775839. doi: 10.1155/jt/6775839. eCollection 2025.
Chemotherapy-induced hepatotoxicity remains a significant challenge in cancer treatment, limiting the clinical use of potent anticancer agents like doxorubicin (DOX) and paclitaxel (PAC). This study investigated the hepatoprotective effects of catechin (CAT), a natural flavonoid antioxidant, against DOX- and PAC-induced liver toxicity. Male Wistar rats were divided into five groups: control, DOX + PAC-treated, CAT-only, and two groups receiving CAT (20 or 40 mg/kg) in combination with DOX + PAC. Hepatic function was assessed through liver enzyme levels, oxidative stress biomarkers, and histopathological examination. Results showed that DOX + PAC treatment significantly elevated serum levels of ALT, AST, and ALP, indicating hepatocellular damage. Oxidative stress markers, including malondialdehyde (MDA) and nuclear factor kappa B (NF-κB), were also increased, while antioxidant defenses such as glutathione (GSH) and catalase were depleted. CAT coadministration, particularly at 40 mg/kg, markedly reduced oxidative damage, restored hepatic enzyme levels, and mitigated histopathological alterations, including congestion, hepatocyte degeneration, and inflammatory infiltration. Moreover, CAT reduced NF-κB expression, suggesting an anti-inflammatory effect. These findings demonstrate that CAT effectively protects against DOX- and PAC-induced hepatotoxicity by enhancing antioxidant defense mechanisms and reducing inflammation. Given its hepatoprotective potential, CAT may serve as a complementary therapeutic strategy to enhance chemotherapy tolerance.
化疗引起的肝毒性仍然是癌症治疗中的一个重大挑战,限制了阿霉素(DOX)和紫杉醇(PAC)等强效抗癌药物的临床应用。本研究调查了天然类黄酮抗氧化剂儿茶素(CAT)对DOX和PAC诱导的肝毒性的保肝作用。将雄性Wistar大鼠分为五组:对照组、DOX+PAC处理组、单独使用CAT组以及两组分别接受20或40mg/kg CAT与DOX+PAC联合使用的组。通过肝酶水平、氧化应激生物标志物和组织病理学检查评估肝功能。结果显示,DOX+PAC处理显著提高了血清ALT、AST和ALP水平,表明肝细胞受损。包括丙二醛(MDA)和核因子κB(NF-κB)在内的氧化应激标志物也增加,而谷胱甘肽(GSH)和过氧化氢酶等抗氧化防御物质减少。CAT联合给药,尤其是40mg/kg时,显著减少了氧化损伤,恢复了肝酶水平,并减轻了组织病理学改变,包括充血、肝细胞变性和炎症浸润。此外,CAT降低了NF-κB表达,表明具有抗炎作用。这些发现表明,CAT通过增强抗氧化防御机制和减轻炎症,有效保护肝脏免受DOX和PAC诱导的肝毒性。鉴于其保肝潜力,CAT可作为一种辅助治疗策略,以提高化疗耐受性。