Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin

Huang, Chien‐Hsun; Wang, Fu-Ting; Chan, Wen‐Hsiung

doi:10.1002/tox.22724

Cited by 16 publications

(6 citation statements)

References 62 publications

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“…The data indicated that exposure to OTA through feed leads to apoptosis, similar to observations made in other studies [46,47]. Some other studies have reported that OTA-contaminated diets had a significant effect on LDH levels, Caspase3 activities, AKT levels, and numbers of apoptotic nuclei [48,49]. Here, it was demonstrated that mRNA expressions of Bax, P53, and Caspase3 were increased in the OTA-exposed kidneys, while levels of PI3K, AKT, and Bcl-2 decreased.…”

Section: Oxidative Medicine and Cellular Longevitysupporting

confidence: 88%

Selenium Yeast Alleviates Ochratoxin A-Induced Apoptosis and Oxidative Stress via Modulation of the PI3K/AKT and Nrf2/Keap1 Signaling Pathways in the Kidneys of Chickens

Cao²,

Guo

et al. 2020

Oxidative Medicine and Cellular Longevity

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The purpose of this study was to investigate the protective effect and mechanism of yeast selenium (Se-Y) on ochratoxin- (OTA-) induced nephrotoxicity of chickens. A total of 80 one-day-old healthy chickens were randomly divided into 4 equal groups: control, OTA (50 μg/kg OTA), Se-Y (0.4 mg/kg Se-Y), and OTA+Se-Y (50 μg/kg OTA+0.4 mg/kg Se-Y). In the OTA chickens, differences in body weight, kidney coefficient, biochemical histological analysis, antioxidant capability, and the expression levels of the PI3K/AKT and Nrf2/Keap1 signaling pathway-related genes were observed. The levels of total superoxide dismutase (T-SOD), antioxidant capacity (T-AOC), catalase (CAT), and glutathione (T-GSH) significantly decreased, but the malondialdehyde (MDA) level of the kidneys significantly increased in the OTA treatment group. More importantly, treatment with Se-Y improved the antioxidant enzyme activities within the kidneys of chickens exposed to OTA. In addition, administration of OTA resulted in apoptosis and was associated with decreased expression of AKT, PI3K, and Bcl-2, which in turn enhanced expression of Caspase3, Bax, and P53. However, Se-Y improved the antioxidant defense system through activation of the Nrf2/Keap1 signaling pathway. Gene expression of Nrf2 and its target genes (HO-1, GSH-px, GLRX2, MnSOD, and CAT) was downregulated following OTA exposure. Conversely, Se-Y treatment resulted in a significant upregulation of the same genes. Besides, significant downregulations of protein expression of HO-1, CAT, MnSOD, Nrf2, and Bcl-2 and a significant upregulation of Caspase3 and Bax levels were observed after contaminated with OTA. Notably, OTA-induced apoptosis and oxidative damage in the kidney of chickens were reverted back to normal level in the OTA+Se-Y group. Taken together, the data suggest that Se-Y alleviates OTA-induced nephrotoxicity in chickens, possibly through the activation of the PI3K/AKT and Nrf2/Keap1 signaling pathways.

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Section: Oxidative Medicine and Cellular Longevitysupporting

confidence: 88%

Selenium Yeast Alleviates Ochratoxin A-Induced Apoptosis and Oxidative Stress via Modulation of the PI3K/AKT and Nrf2/Keap1 Signaling Pathways in the Kidneys of Chickens

Cao²,

Guo

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…At both micro and nanomolar concentrations, OTA boosted blastocyst mitochondrial function and reduced mitochondria/ROS colocalization. Mouse blastocysts, exposed in vitro for 24 h to OTA during the morula/blastocyst transition exhibited loss of mitochondria membrane potential and increased ROS generation (Hsuuw et al 2013;Huang et al 2019). A possible explanation of discrepancies with our study could be the exposure phase.…”

Section: Discussioncontrasting

confidence: 83%

Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

et al. 2020

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The genotoxic and nephrotoxic mycotoxin Ochratoxin A (OTA) has also been reported to have adverse effects on oocyte maturation and embryo development. Previous studies on the effects of OTA on female fertility have used micromolar concentrations, but no information is available to date on effects in a more relevant nanomolar range. This study used a juvenile sheep model to evaluate the effects of oocyte exposure to low levels of OTA on maturation, fertilization, and embryo development. Further, it was investigated whether different mechanisms of action of OTA could be responsible for varying toxic effects at different levels of exposure. Cumulus-oocyte-complexes (COCs) were exposed to 10 μmol/L–0.1 nmol/L OTA during in vitro maturation and evaluated for cumulus viability, oocyte maturation, and bioenergetic/oxidative status. COCs were subjected to in vitro fertilization, embryo culture, and embryo quality assessment via morphology, viability, bioenergetic/oxidative status, and time-lapse monitoring. At micromolar concentrations, OTA induced cytotoxic effects, by reducing cumulus expansion and oocyte maturation. OTA altered temporospatial dynamics of zygote pronuclear formation and embryo morphokinetics. Blastocysts, even morphologically normal, were found to undergo collapse events, which were probably related to boosted blastocyst mitochondrial activity. At nanomolar concentrations, OTA did not affect COC morpho-functional parameters, but impaired oocyte ability to prevent polyspermy and increased blastocyst apoptosis. In conclusion, in the female germ cell, cytotoxic nonspecific effects characterize OTA-induced toxicity at high exposure levels, whereas fine tuning-mode effects, not associated with altered cell viability and integrity, characterize OTA toxic action at low levels.

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“…Bax and Bcl-2 are two important proteins that respond to mitochondrial apoptosis; Bax is a proapoptotic protein, and Bcl-2 is an antiapoptotic protein [38,43]. In addition, myocardial injury in rats causes apoptosis by activating the caspase family [44][45][46]. This study detected cardiomyocyte apoptosis by TUNEL assay…”

Section: Discussionmentioning

confidence: 92%

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

Cui

et al. 2020

Oxidative Medicine and Cellular Longevity

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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.

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Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin

Cited by 16 publications

References 62 publications

Selenium Yeast Alleviates Ochratoxin A-Induced Apoptosis and Oxidative Stress via Modulation of the PI3K/AKT and Nrf2/Keap1 Signaling Pathways in the Kidneys of Chickens

Selenium Yeast Alleviates Ochratoxin A-Induced Apoptosis and Oxidative Stress via Modulation of the PI3K/AKT and Nrf2/Keap1 Signaling Pathways in the Kidneys of Chickens

Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

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

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