Crocin ameliorates arsenic trioxide‑induced cardiotoxicity via Keap1-Nrf2/HO-1 pathway: Reducing oxidative stress, inflammation, and apoptosis.
Arsenic trioxide (ATO) is an excellent therapy for acute promyelocytic leukemia; however, its use is limited due to its cardiotoxicity. Crocin (CRO) possesses abundant pharmacological and biological properties, including antioxidant, anti-inflammatory, and anti-apoptotic. This study examined the cardioprotective effects of crocin and explored their mechanistic involvement in ATO-induced cardiotoxicity. Forty-eight male rats were treated with ATO to induce cardiotoxicity. In combination with ATO, CRO were given to evaluate its cardioprotection. The results demonstrated that CRO administration not only diminished QTc prolongation, myocardial enzymes and Troponin T levels but also improved histopathological results. CRO administration reduced reactive oxygen species generation. However, the CRO administration caused an increase in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and total sulphydryl levels and a decrease in malondialdehyde content, gamma glutamyl transferase and lipid hydroperoxides levels and proinflammatory cytokines. Importantly, immunohistochemical analysis, real time PCR and western blotting showed a reduction in Caspase-3 and Bcl-2-associated X protein expressions and enhancement of B cell lymphoma-2 expression. Real time PCR and western blotting showed a reduction in proinflammatory cytokines. Moreover, CRO caused an activation in nuclear factor erythroid-2 related factor 2, leading to enhanced Kelch-like ECH-associated protein 1, heme oxygenase-1 and nicotinamide adenine dinucleotide quinone dehydrogenase 1 expressions involved in Nrf2 signaling during ATO-induced cardiotoxicity. CRO was shown to ameliorate ATO-induced cardiotoxicity. The mechanisms for CRO amelioration of cardiotoxicity due to inflammation, oxidative damage, and apoptosis may occur via an up-regulated Keap1-Nrf2/HO-1 signaling pathway.
['Liang|Yingran|Y|', 'Zheng|Bin|B|', 'Li|Jinghan|J|', 'Shi|Jing|J|', 'Chu|Li|L|', 'Han|Xue|X|', 'Chu|Xi|X|', 'Zhang|Xuan|X|', 'Zhang|Jianping|J|']
D000818:Animals D000893:Anti-Inflammatory Agents D017209:Apoptosis D000077237:Arsenic Trioxide D066126:Cardiotoxicity D002338:Carotenoids D004562:Electrocardiography D006419:Heme Oxygenase (Decyclizing) D000072019:Kelch-Like ECH-Associated Protein 1 D008297:Male D009206:Myocardium D051267:NF-E2-Related Factor 2 D018384:Oxidative Stress D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D015398:Signal Transduction
Crocin Cardiotoxicity Keap1-Nrf2/HO-1 Arsenic trioxide