Apigenin attenuates Aluminum phosphide-induced cytotoxicity via reducing mitochondrial/Lysosomal damages and oxidative stress in rat Cardiomyocytes

Jahedsani, Asal; Khezri, Saleh; Ahangari, Mahsa; Bakhshii, Saba; Salimi, Ahmad

doi:10.1016/j.pestbp.2020.104585

Cited by 20 publications

(12 citation statements)

References 34 publications

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“…Our results on isolated cardiomyocytes and mitochondria showed that AlP induces mitochondrial toxicity and oxidative stress. Our findings are in accordance with previous reports that showed AlP that causes oxidative damages and mitochondrial dysfunction (Jahedsani et al, 2020;Khezri et al, 2020).…”

Section: Discussionsupporting

confidence: 94%

“…The Myr analogs are acacetin, chrysin, apigenin, luteolin, kaempferol, naringenin, and quercetin, which have shown similar effects ( Taheri et al, 2020 ). Recently, we showed that apigenin and chrysin have a similar effect on isolated cardiomyocytes and mitochondria against AlP ( Jahedsani et al, 2020 ; Khezri et al, 2020 ). It has been reported that quercetin, a very similar analog to Myr, can act as an inhibitor of the MPT pore, and the same effect of Myr was proved in this study ( De Marchi et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

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

2021

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Oxidative stress and mitochondrial dysfunction are involved in the mechanisms of cardiac toxicity induced by aluminum phosphide (AlP). AlP-induced cardiotoxicity leads to cardiomyocyte death, cardiomyopathy, cardiac dysfunction, and eventually severe heart failure and death. Importantly, protecting cardiomyocytes from death resulting from AlP is vital for improving survival. It has been reported that flavonoids such as myricetin (Myr) act as modifiers of mitochondrial function and prevent mitochondrial damage resulting from many insults and subsequent cell dysfunction. In this study, the ameliorative effect of Myr, as an important antioxidant and mitochondrial protective agent, was investigated in cardiomyocytes and mitochondria isolated from rat heart against AlP-induced toxicity, oxidative stress, and mitochondrial dysfunction. Treatment of AlP (20 μg/ml) significantly increased cytotoxicity; reduced glutathione (GSH) depletion, cellular reactive oxygen species (ROS) formation, malondialdehyde (MDA) level, ATP depletion, caspase-3 activation, mitochondrial membrane potential (ΔΨm) collapse, and lysosomal dysfunction; and decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in intact cardiomyocytes. Also, treatment of AlP (20 μg/ml) significantly increased mitochondrial dysfunction and swelling in isolated mitochondria. Myr (80 µM) appeared to ameliorate AlP-induced cytotoxicity in isolated cardiomyocytes; significantly lessened the AlP-stimulated intracellular ROS and MDA production and depletion of GSH; and increased the activities of SOD, CAT, and GSH-Px. Furthermore, Myr (40 and 80 µM) lowered AlP-induced lysosomal/mitochondrial dysfunction, ATP depletion, and caspase-3 activation. In the light of these findings, we concluded that Myr through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted an ameliorative role in AlP-induced toxicity in isolated cardiomyocytes and mitochondria, and it would be valuable to examine its in vivo effects.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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

2021

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“…Free radicals induce malfunction of macromolecules, alteration of membrane permeability, LPO, cellular damages, and cell death. 51–54 Our results showed that co-treatment with various doses of exenatide (0.05, 0.1, and 0.2 mg/kg) reduced LPO levels in rats poisoned with AlP during both times. This finding was in accordance with others mentioning anti-oxidant effect of exenatide.…”

Section: Discussionmentioning

confidence: 65%

Electrocardiographic, hemodynamic, and biochemical evidence on the protective effects of exenatide against phosphine-induced cardiotoxicity in rat model

et al. 2021

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Aluminum phosphide (AlP) poisoning can be deadly in most cases targeting the heart. To overcome AlP toxicity, exenatide has been studied in the present study due to its pleiotropic effects on cardiac damages. In this study, the rats were exposed to LD50 of AlP (10 mg/kg) by gavage, and exenatide at doses (0.05, 0.1, and 0.2 mg/kg) injected intraperitoneally 30 min after poisoning. The cardiac parameters including heart rate (HR), blood pressure (BP), QRS, corrected QT (QTc), and ST were monitored for 180 min. Blood glucose level was measured in the study groups 30 min after exenatide injection. Evaluation of biochemical parameters including mitochondrial complexes I, II, and IV activities, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, malondialdehyde (MDA), apoptosis, lactate, troponin I, and brain natriuretic peptide (BNP) was done on heart tissues after 12 and 24 h. Additionally, the tissues were analyzed for any pathological damages including necrosis, hemorrhage, or hyperemia 24 h post-treatment. Our results showed that AlP-induced HR, BP, and electrocardiographic changes were improved by exenatide at all doses. The blood glucose levels of poisoned animals reached control levels after exenatide treatment. Besides, treatment with exenatide at all doses improved complexes I and IV activity, ADP/ATP ratio, and apoptosis. Malondialdehyde, lactate, troponin I, and BNP levels were also diminished after exenatide co-treatment in poisoned animals. On the other hand, administration of exenatide doses improved the histopathology of AlP-induced tissues. Based on our findings, exenatide has a protective effect against phosphine-induced cardiotoxicity in an almost dose-dependent way. However, further investigations are needed on the potential clinical use of exenatide in this poisoning.

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“…Jahedsani et al (2020) reported strong cardio-protective effects of apigenin in rats cardiomyocytes. Isolated cardinomyocytes from rats heart were treated with different concentration of aluminum phosphide (AlP) (0-200 µg/mL), and cryoprotective assay was evaluated after exposure of treated cardinomyocytes with apigenin (5-100 µM)for 3 hr at 37°C.…”

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confidence: 99%

Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review

Kashyap

Shikha²,

Thakur³

et al. 2021

Journal of Food Biochemistry

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Several chronic diseases like cancer, diabetes, stroke, neurodegenerative disorders, etc. are rising globally at a faster rate basically due to the increasing free radicals overproduction and oxidative stress from current lifestyle, but can be suppressed or inhibited by antioxidant compounds (Chaturvedi & Beal, 2013;Halliwell, 2012). Now-a-days, the natural antioxidants have a higher demand than the synthetic ones (Kashyap et al., 2017). Among them, flavonoids have a higher value due to their role in human health. They are plantderived compounds having exotic colors which are secondarily produced from phenylalanine (Havsteen, 2002). They are the largest family of naturally occurring polyphenols which include the flavones, flavonols, flavanones, flavanols, isoflavonoids, and anthocyanidins

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Apigenin attenuates Aluminum phosphide-induced cytotoxicity via reducing mitochondrial/Lysosomal damages and oxidative stress in rat Cardiomyocytes

Cited by 20 publications

References 34 publications

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

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

Electrocardiographic, hemodynamic, and biochemical evidence on the protective effects of exenatide against phosphine-induced cardiotoxicity in rat model

Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review

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