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

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.

Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro

“…Bax and cleaved caspase-3) and an upregulation of anti-apoptotic proteins (eg. Bcl-2 and survivin) 50 , 51 . Treatment with Ax has also been reported to decrease the cathepsin B activity 27 .…”

Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress

“…Under normal conditions, NRF2 combines with KEAP1 in the cytoplasm, where KEAP1 acts as an inhibitor of NRF2 [ 30 ]. Many stimuli lead to the dissociation of KEAP1 from NRF2, and NRF2 can then translocate to the nucleus to activate transcription of NRF2-dependent genes associated with anti-inflammation and antioxidation [ 42 , 43 ]. Itaconate increases the alkylation of cysteine residues 151, 257, 288, 273, and 297 on KEAP1, which enhances the degradation of KEAP1 and leads to further NRF2 activation [ 30 ].…”

Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging

“…ASX exerts various cytoprotective effects by promoting Nrf2/ARE signaling. In a mouse model of cardiac injury, induced by ochratoxin A, ASX played a protective role on the myocardium through the activation of the Nrf2/ARE signaling pathway, together with modulation of the mitochondria-mediated apoptosis pathway [ 58 ].…”