Health Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Department of Pharmacology, Faculty of Medicine, Zawia University, Zawiya, Libya.
Arch Biochem Biophys. 2021 Jun 15;704:108866. doi: 10.1016/j.abb.2021.108866. Epub 2021 Apr 14.
A tyrosine kinase inhibitor Imatinib (IM) is used in the treatment of different varieties of cancers. The current study was designed to explore the beneficial role of l-carnitine against IM-induced cardiotoxicity in rats. Male albino rats received IM (40 mg/kg, i.p.) either alone or/in combination with l-carnitine (100 mg/kg, i.p.) for 7 days. IM increased serum inflammatory cytokines, concomitant with activation of cardiac MAPK, α-SMA, malondialdehyde (MDA) and nitric oxide(NO), decreased cardiac peroxisome proliferator-activated receptor-γ (PPAR-γ) level, superoxide dismutase (SOD) activity, and glutathione (GSH) content. The expression levels of Bcl-2 and PDGF were significantly decreased, while the expression levels of CTGF and BAX were significantly increased in the IM group. The l-carnitine treatment successfully protected the heart as indicated by the improvement of the biochemical and histopathological parameters. l-carnitine didn't affect the serum concentration of IM and increased intracellular concentration in the combination-treated group as measured by the mass spectrometer. Conclusion: l-carnitine abrogated IM-induced cardiac damage and apoptosis via PDGF/PPARγ/MAPK pathways.
一种酪氨酸激酶抑制剂伊马替尼（IM）用于治疗多种癌症。本研究旨在探讨左旋肉碱对 IM 诱导的大鼠心脏毒性的有益作用。雄性白化大鼠单独或联合给予 IM（40mg/kg，腹腔注射）或左旋肉碱（100mg/kg，腹腔注射）7 天。IM 增加了血清炎症细胞因子，同时激活了心脏 MAPK、α-SMA、丙二醛（MDA）和一氧化氮（NO），降低了心脏过氧化物酶体增殖物激活受体-γ（PPAR-γ）水平、超氧化物歧化酶（SOD）活性和谷胱甘肽（GSH）含量。IM 组 Bcl-2 和 PDGF 的表达水平显著降低，而 CTGF 和 BAX 的表达水平显著升高。左旋肉碱治疗成功地保护了心脏，表现为生化和组织病理学参数的改善。左旋肉碱通过质谱仪测量未影响 IM 的血清浓度，并增加了联合治疗组的细胞内浓度。结论：左旋肉碱通过 PDGF/PPARγ/MAPK 通路阻断 IM 诱导的心脏损伤和细胞凋亡。
