Chrysin ameliorates aluminum phosphide‐induced oxidative stress and mitochondrial damages in rat cardiomyocytes and isolated mitochondria

Abstract

Apart from the anticancer, antioxidant, anti‐inflammatory effects, and inhibition of aromatase, chrysin is involved in the protection of cardiovascular disorders. Cardiovascular complications are the main cause of death induced by aluminum phosphide (AlP) which is related to oxidative stress and mitochondrial damages. For this purpose, we investigated the effect of chrysin as an antioxidant and mitochondrial protective agent against AlP‐induced toxicity in isolated cardiomyocytes and mitochondria obtained from rat heart ventricular. Using by biochemical and flow cytometry, cell viability, reactive oxygen species (ROS) formation, mitochondria membrane potential (MMP), lysosomal membrane integrity, malondialdehyde (MDA) content, and glutathione (GSH) and oxidized glutathione (GSSG) content were measured in isolated cardiomyocytes. Also, mitochondrial toxicity parameters such as mitochondrial NADH/succinate dehydrogenase activity, mitochondrial swelling, ROS formation, MMP collapse, and lipid peroxidation were analyzed in isolated mitochondria. Our results showed that the administration of chrysin (up to 10 μM) efficiently decreased (P < 0.05) cytotoxicity, oxidative, lysosomal, and mitochondrial damages induced by AlP, in isolated cardiomyocytes. Also, our finding in isolated mitochondria showed that chrysin (up to 10 μM) significantly (P < 0.05) decreased AlP‐induced mitochondrial toxicity. These findings demonstrated that chrysin as an antioxidant and mitochondrial protective agent exert protective effect in wild‐type cardiomyocyte treated with AlP. It was concluded that chrysin significantly reduced the toxicity of AlP in isolated cardiomyocytes and mitochondria. Due to the very low toxicity of chrysin for humans, it could be a promising agent in treatment of AlP poisoning.

Antioxidant Potential and Inhibition of Mitochondrial Permeability Transition Pore by Myricetin Reduces Aluminium Phosphide-Induced Cytotoxicity and Mitochondrial Impairments

“…The experimental groups were categorized into six groups in the current study. 1) In the control group, cardiomyocytes were treated with 0.05% DMSO for 3 h. 2) In the AlP group, cardiomyocytes were treated with 20 μg/ml of AlP (IC 50 3 h) for 3 h according to our previous study ( Khezri et al, 2020 ). 3) In the AlP + Myr group, cardiomyocytes were cotreated with 20 μg/ml of AlP and 20 μM of Myr for 3 h. 4) In the AlP + Myr group, cardiomyocytes were cotreated with 20 μg/ml of AlP and 40 μM of Myr for 3 h. 5) In the AlP + Myr group, cardiomyocytes were cotreated with 20 μg/ml of AlP and 80 μM of Myr for 3 h. 6) In the Myr group, cardiomyocytes were treated with 80 μM of Myr for 3 h.…”

Recent Progress in Environmental Toxins-Induced Cardiotoxicity and Protective Potential of Natural Products

“…The protective effect of chrysin on doxorubicin-induced cardiotoxicity is exerted via the mitochondrial apoptosis pathway and the inhibition of oxidative stress (Samarghandian et al, 2017). Similarly, Khezri et al found that treatment with chrysin significantly reduced the formation of ROS, lysosomal damage, mitochondrial damage and lipid peroxidation induced by ALP (Khezri et al, 2020). A recent study conducted by Jahedsani et al showed that apigenin also has the same protective effect as chrysin against ALP-induced myocardial damage (Mahajan et al, 2017).…”

Mitochondrial Metal Ion Transport in Cell Metabolism and Disease

“…These questions have not yet been fully answered and require further investigation. For instance, aluminum is considered to be an inducer of the mitochondrial permeability transition [ 179 ], and aluminum phosphide can induce oxidative stress and mitochondrial damages in cardiomyocytes and isolated mitochondria [ 180 ]. Unfortunately, the transport of mitochondrial aluminum ions is still unclear.…”