Doxorubicin (DOX) is one of the most widely used chemotherapeutic drugs, but its cardiotoxicity has been shown to be a dose-restricting factor during therapy. Finding new agents for reducing these complications is still in critical need. The current study aimed to evaluate the possible cardioprotective effect of hemin (HEM) in DOX-induced cardiotoxicity and exploring the role of toll like receptor-5/nuclear factor kappa-B/tumor necrosis factor-alpha (TLR-5/NF-κB/TNF-α) and nuclear factor erythroid 2-related factor-2/hemeoxygenase-1 (Nrf-2/HO-1) signaling pathways in mediating such effect. Wistar albino rats were randomly divided into five groups. They were administered DOX by interaperitoneal (i.p.) injection (15 mg/kg) on the 5th day of the experiment with or without HEM in different doses (2.5, 5, 10 mg/kg/day) i.p. for 7 days. Results showed that the DOX group had cardiotoxicity as manifested by a significant increase in cardiac enzymes, malondialdehyde (MDA), TLR-5, NF-κB, TNF-α, and cleaved caspase-3 levels with toxic histopathological changes. Based on these findings, HEM succeeded in reducing DOX-induced cardiotoxicity in a dose-dependent effect by stimulation of Nrf-2/HO-1 and inhibition of TLR-5/NF-κB/TNF-α pathways with subsequent antioxidant, anti-inflammatory, and anti-apoptotic effects.

阿霉素（DOX）是最广泛使用的化疗药物之一，但其心脏毒性已被证明是治疗期间的剂量限制因素。仍然迫切需要寻找新的药物来减少这些并发症。本研究旨在评估血红素 (HEM) 在 DOX 诱导的心脏毒性中可能的心脏保护作用，并探索 Toll 样受体 5/核因子 kappa-B/肿瘤坏死因子-α (TLR-5/NF-κB) 的作用。 /TNF-α) 和核因子红细胞 2 相关因子-2/血氧合酶-1 (Nrf-2/HO-1) 信号通路介导这种作用。Wistar白化大鼠被随机分为五组。他们通过腹膜间（ip) 在实验的第 5 天注射 (15 mg/kg)，有或没有 HEM，不同剂量 (2.5, 5, 10 mg/kg/day) ip共7 天。结果表明，DOX 组具有心脏毒性，表现为心肌酶、丙二醛 (MDA)、TLR-5、NF-κB、TNF-α 和裂解的 caspase-3 水平显着增加，并伴有毒性组织病理学变化。基于这些发现，HEM 通过刺激 Nrf-2/HO-1 和抑制 TLR-5/NF-κB/TNF-α 通路以及随后的抗氧化、抗炎症和抗凋亡作用。