Soltani Hekmat Ava, Hekmat Maryam, Ramezanipour Sepehr, Javanmardi Kazem
Department of Physiology, Fasa University of Medical Sciences, Fasa, Iran.
Department of Dermatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
BMC Pharmacol Toxicol. 2025 May 3;26(1):95. doi: 10.1186/s40360-025-00932-0.
Doxorubicin (DOX), a common chemotherapeutic agent, is often associated with dose-limiting hepatotoxicity. Alamandine, a peptide of the renin-angiotensin system, has shown antioxidant and anti-inflammatory properties that may counteract these adverse effects.
This study investigated the protective effects of alamandine on DOX-induced liver injury in rats.
Male Wistar rats received DOX (3.75 mg/kg intraperitoneally) on days 14, 21, 28, and 35, reaching a cumulative dose of 15 mg/kg. Alamandine (50 µg/kg/day) was administered continuously via mini-osmotic pumps for 42 days. Liver toxicity was assessed through biochemical measurements of oxidative stress markers, inflammatory cytokines, and liver enzymes, as well as histological examination.
DOX administration significantly increased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels while reducing superoxide dismutase (SOD) and catalase (CAT) activity. Histological analysis revealed hydropic degeneration and hepatocyte necrosis. Alamandine co-treatment restored SOD and CAT activity, reduced MDA and inflammatory markers, and normalized liver enzyme levels, indicating significant hepatoprotection. Furthermore, treatment with alamandine reduced the expression of pro-inflammatory cytokines IL-6, IL-1, and NF-κB induced by DOX, while p53 expression remained unchanged.
Alamandine effectively mitigates DOX-induced hepatotoxicity, demonstrating its therapeutic potential as an adjunctive agent in chemotherapy through its antioxidant and anti-inflammatory mechanisms.
阿霉素（DOX）是一种常见的化疗药物，常伴有剂量限制性肝毒性。阿拉曼丁是肾素-血管紧张素系统的一种肽，已显示出抗氧化和抗炎特性，可能抵消这些不良反应。
本研究调查了阿拉曼丁对阿霉素诱导的大鼠肝损伤的保护作用。
雄性Wistar大鼠在第14、21、28和35天腹腔注射阿霉素（3.75mg/kg），累积剂量达到15mg/kg。阿拉曼丁（50μg/kg/天）通过微型渗透泵连续给药42天。通过对氧化应激标志物、炎性细胞因子和肝酶进行生化检测以及组织学检查来评估肝毒性。
给予阿霉素显著增加了血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和丙二醛（MDA）水平，同时降低了超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。组织学分析显示细胞水肿变性和肝细胞坏死。阿拉曼丁联合治疗恢复了SOD和CAT活性，降低了MDA和炎性标志物水平，并使肝酶水平恢复正常，表明具有显著的肝脏保护作用。此外，阿拉曼丁治疗降低了阿霉素诱导的促炎细胞因子IL-6、IL-1和NF-κB的表达，而p53表达保持不变。
阿拉曼丁有效减轻阿霉素诱导的肝毒性，通过其抗氧化和抗炎机制证明了其作为化疗辅助药物的治疗潜力。
