Effect of Catechin on Hepatotoxicity Induced by Combined Doxorubicin and Paclitaxel Treatment.

IF 3 Q2 TOXICOLOGY
Journal of Toxicology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI:10.1155/jt/6775839
Shayan Shwan Mohammed-Rashid, Hiewa Othman Dyary
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引用次数: 0

Abstract

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.

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儿茶素对阿霉素与紫杉醇联合治疗肝毒性的影响。
化疗引起的肝毒性仍然是癌症治疗中的一个重大挑战,限制了强效抗癌药物如阿霉素(DOX)和紫杉醇(PAC)的临床使用。本研究探讨了天然类黄酮抗氧化剂儿茶素(CAT)对DOX-和pac诱导的肝毒性的保护作用。雄性Wistar大鼠分为对照组、DOX + PAC处理组、CAT单独处理组和CAT(20或40 mg/kg)联合DOX + PAC治疗组。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治疗显著升高血清ALT、AST和ALP水平,提示肝细胞损伤。氧化应激标志物丙二醛(MDA)和核因子κB (NF-κB)升高,抗氧化防御能力如谷胱甘肽(GSH)和过氧化氢酶减少。CAT共给药,特别是在40 mg/kg的剂量下,可显著降低氧化损伤,恢复肝酶水平,减轻组织病理学改变,包括充血、肝细胞变性和炎症浸润。此外,CAT可降低NF-κB的表达,提示其具有抗炎作用。这些发现表明,CAT通过增强抗氧化防御机制和减少炎症,有效地预防DOX-和pac诱导的肝毒性。鉴于其肝保护潜力,CAT可能作为一种补充治疗策略,以提高化疗耐受性。
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来源期刊
Journal of Toxicology
Journal of Toxicology TOXICOLOGY-
CiteScore
5.50
自引率
3.40%
发文量
0
审稿时长
10 weeks
期刊介绍: Journal of Toxicology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of toxicological sciences. The journal will consider articles looking at the structure, function, and mechanism of agents that are toxic to humans and/or animals, as well as toxicological medicine, risk assessment, safety evaluation, and environmental health.
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