Protective Effect Of Astaxanthin On Ochratoxin A-induced Cardiac Injury In Mice

Purpose:Ochratoxin A（OTA）is a kind of toxic substance in mycotoxins,which is widely present in food and feed.OTA not only caused huge economic losses to the production of animal husbandry,but also the health problems caused by the toxin has been the focus of attention worldwide.Studies have shown that in the blood,OTA will bind firmly to serum proteins,causing poor blood coagulation,and then causing animal myocardial damage through the effects of oxidative stress and apoptosis.Astaxanthin（ASX）is a super antioxidant in carotenoids.It can protect cells from oxidative damage and improve the balance between oxidants and the body’s antioxidant system.This study evaluated the protective mechanism of astaxanthin on ochratoxin A-induced heart damage in mice.Methods:80 mice were randomly divided into 4 groups:control group（0.1 m L olive oil+0.1 m L Na HCO₂）,OTA group（OTA,5 mg/kg）,ASX group（ASX,100 mg/kg）and ASX+OTA group（ASX 100 mg/kg,0.1 m L OTA 5 mg/kg）.Modeling cycle:28 days（administration for 5 days,drug withdrawal for 2 days）,free intake of food and water.Tests on mouse electrocardiogram,body weight,heart weight,histopathological section,tissue oxidation index,serum biochemical index,transmission electron microscope,Tunel and Western-blot tests to detect the detoxification effect of OTA on myocardial injury and ASX.Results:（1）OTA reduced mouse body weight and heart weight,mouse heart rate and heart tissue superoxide dismutase（SOD）,catalase（CAT）and reduced glutathione（GSH）Content,increased the apoptotic rate of cardiomyocytes in mice,serum creatine kinase（CK）,creatine kinase-isoenzyme（CK-MB）,lactate dehydrogenase（LDH）and malondialdehyde（MDA）content.（2）The intervention of ASX improved the heart rate,myocardial enzymes and antioxidant levels of mice.Pathology and Tunel results show that ASX has a protective effect on OTA-induced myocardial injury.（3）Western-blot results showed that the OTA group can up-regulate the protein expression of Keap1,Bax,Caspase3,and Caspase9,and down-regulate the protein expression of Nrf2,HO-1,and Bcl-2.（4）ASX plays a protective role by changing the expression of Keap1,Nrf2,HO-1,Bax,Bcl-2,Caspase3 and Caspase9 proteins.Conclusion:ASX has a protective effect on OTA-induced heart injury in mice;the mechanism of ASX on myocardium is through the Keap1-Nrf2 signaling pathway and mitochondrial-mediated apoptosis pathway.