Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt.
Department of Medical Histology and Cell Biology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Mol Cell Biochem. 2023 Oct;478(10):2319-2335. doi: 10.1007/s11010-023-04662-x. Epub 2023 Jan 31.
Cyclophosphamide (CPA) is a classical chemotherapeutic drug widely used as an anticancer and immunosuppressive agent. However, it is frequently associated with significant toxicities to the normal cells of different organs, including the lung and heart. Lansoprazole (LPZ), a proton pump inhibitor (PPI), possesses antioxidant and anti-inflammatory properties. The current study investigated how LPZ protects against CPA-induced cardiac and pulmonary damage, focusing on PPARγ, Nrf2, HO-1, cytoglobin, PI3K/AKT, and NF-κB signaling. Animals were randomly assigned into four groups: normal control group (received vehicle), LPZ only group (Rats received LPZ at a dose of 50 mg/kg/day P.O. for 10 days), CPA group (CPA was administered (200 mg/kg) as a single i.p. injection on the 7th day), and cotreatment group (LPZ plus CPA). Histopathological and biochemical analyses were conducted. Our results revealed that LPZ treatment revoked CPA-induced heart and lung histopathological alterations. Also, LPZ potently mitigated CPA-induced cardiac and pulmonary oxidative stress through the activation of PPARγ, Nrf2/HO-1, cytoglobin, and PI3K/AKT signaling pathways. Also, LPZ effectively suppressed inflammatory response as evidenced by down-regulating the inflammatory strategic controller NF-κB, MPO, and pro-inflammatory cytokines. The present findings could provide a mechanistic basis for understanding LPZ's role in CPA-induced cardiopulmonary injury through the alleviation of oxidative stress and inflammatory burden.
环磷酰胺（CPA）是一种经典的化疗药物，广泛用于抗癌和免疫抑制。然而，它经常与不同器官（包括肺和心脏）的正常细胞产生显著的毒性有关。兰索拉唑（LPZ）是一种质子泵抑制剂（PPI），具有抗氧化和抗炎特性。本研究探讨了 LPZ 如何通过 PPARγ、Nrf2、HO-1、细胞色素蛋白、PI3K/AKT 和 NF-κB 信号通路来保护 CPA 诱导的心脏和肺损伤。动物被随机分为四组：正常对照组（给予载体）、LPZ 组（大鼠每天给予 LPZ 50mg/kg，口服 10 天）、CPA 组（第 7 天给予 CPA 200mg/kg，腹腔注射一次）和联合治疗组（LPZ 加 CPA）。进行了组织病理学和生化分析。我们的结果表明，LPZ 治疗逆转了 CPA 诱导的心肺组织病理学改变。此外，LPZ 通过激活 PPARγ、Nrf2/HO-1、细胞色素蛋白和 PI3K/AKT 信号通路，有力地减轻了 CPA 诱导的心脏和肺部氧化应激。此外，LPZ 通过下调炎症战略控制器 NF-κB、MPO 和促炎细胞因子，有效抑制了炎症反应。这些发现为理解 LPZ 通过减轻氧化应激和炎症负担在 CPA 诱导的心肺损伤中的作用提供了机制基础。
