Astaxanthin Protects Ochratoxin A-Induced Oxidative Stress and Apoptosis in the Heart via the Nrf2 Pathway.

Gengyuan Cui,Ketao Xu,Danyang Jiao,Yang Guo,Shuhua Yang,Lin Li,Yueli Chen,Weixiang Xu,Beibei Yao,Mingyang Wang,Miao Long,Peng Li

doi:10.1155/2020/7639109

Gengyuan Cui, Ketao Xu + Show 10 more

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https://doi.org/10.1155/2020/7639109

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Abstract

This study assessed the protective mechanism of astaxanthin (ASX) against ochratoxin A- (OTA-) induced cardiac injury in mice. Four groups of mice were established: control group (0.1 mL olive oil + 0.1 mL NaHCO2), OTA group (0.1 mL OTA 5 mg/kg body weight), ASX group (0.1 mL ASX 100 mg/kg body weight), and ASX + OTA group (0.1 mL ASX 100 mg/kg body weight, 2 h later, 0.1 mL OTA 5 mg/kg body weight). The test period lasted for 27 days (7 days of dosing, 2 days of rest). Electrocardiogram, body weight, heart weight, tissue pathology, oxidative markers (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)), biochemical markers (creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH)), electron microscopy, TUNEL, and Western blot tests were used to examine the effects of OTA on myocardial injury and ASX detoxification. The results showed that OTA exposure significantly decreased both body weight and heart weight. OTA induced a decrease in heart rate in mice and decreased tissue concentrations of SOD, CAT, and GSH, while increasing serum concentrations of cardiac enzymes (CK, CK-MB, and LDH) and tissue MDA. ASX improved heart rate, cardiac enzymes, and antioxidant levels in mice. The results of tissue pathology and TUNEL assay showed that ASX protects against OTA-induced myocardial injury. In addition, Western blot results showed that the OTA group upregulated Keap1, Bax, Caspase3, and Caspase9, while it downregulated Nrf2, HO-1, and Bcl-2 protein expression. ASX played a protective role by changing the expression of Keap1, Nrf2, HO-1, Bax, Bcl-2, Caspase3, and Caspase9 proteins. These results indicate that the protective mechanism of ASX on the myocardium works through the Keap1-Nrf2 signaling pathway and mitochondria-mediated apoptosis pathway. This study provides a molecular rationale for the mechanism underlying OTA-induced myocardial injury and the protective effect of ASX on the myocardium.

Highlights

Ochratoxin A (OTA) is a toxic secondary metabolite produced by strains of Aspergillus and Penicillium and is common in food and feed products [1]
Mice in the ASX group showed a highly significant increase in body weight (P < 0:01) and mice in the ASX+OTA group showed a significant increase in body weight (P < 0:05) compared with the OTA group
Mice in the ASX group showed a highly significant increase in heart weight (P < 0:01). These results indicated that OTA damages the heart of mice and decreased their body weight

Summary

Introduction

Ochratoxin A (OTA) is a toxic secondary metabolite produced by strains of Aspergillus and Penicillium and is common in food and feed products (grains, legumes, coffee, dried fruit, beer, wine, and meat) [1]. OTA has good thermal stability, and its toxicity is not degraded within 3 h under high temperature and pressure [3]. Due to this property of OTA, humans and domestic animals are chronically affected by its toxicity, and long-term exposure to low doses of OTA has been shown to exert higher carcinogenic potential than acute exposure to high doses of OTA [2, 4, 5]. Okutan et al reported that low doses of OTA caused pathological damage to the rat heart as well as myocardial cell necrosis, Oxidative Medicine and Cellular Longevity myocardial fiber swelling, and vascular congestion [11]. A protective agent is required to overcome OTA-induced myocardial injury, and elucidating the toxicological mechanism of OTA on cardiac injury is of high clinical value for the prevention and treatment of myocardial injury

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