Effect of L-carnitine on cardiotoxicity and apoptosis induced by imatinib through PDGF/ PPARγ /MAPK pathways

被引：23
作者：
Mansour, Heba H. [1 ]
El Kiki, Shereen M. [1 ]
Ibrahim, Amel B. [2 ]
Omran, Mervat M. [3 ]
机构：
[1] Egyptian Atom Energy Author, Natl Ctr Radiat Res & Technol, Hlth Radiat Res Dept, Cairo, Egypt
[2] Zawia Univ, Fac Med, Dept Pharmacol, Zawiya, Libya
[3] Cairo Univ, Natl Canc Inst, Canc Biol Dept, Pharmacol Unit, Giza, Egypt
来源：
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2021年 / 704卷
关键词：
Imatinib; L-carnitine; MAPK; PDGF; PPAR-γ OXIDATIVE STRESS; GROWTH-FACTOR; CELLS; EXPRESSION; SURVIVAL; TRANSPORTERS; ACTIVATION; RESISTANCE; INHIBITION; MECHANISM;
D O I：
10.1016/j.abb.2021.108866
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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, alpha-SMA, malondialdehyde (MDA) and nitric oxide(NO), decreased cardiac peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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/PPAR gamma/ MAPK pathways.
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页数：9
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