Astaxanthin Protects OTA-Induced Lung Injury in Mice Through the Nrf2/NF-κB Pathway

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2019 Sep 20

PMID 31533259

Citations 16

Authors

Weixiang Xu

Mingyang Wang

Gengyuan Cui

Lin Li

Danyang Jiao

Beibei Yao

Ketao Xu

Yueli Chen

Miao Long

Shuhua Yang

Jianbin He

Affiliations

Soon will be listed here.

Abstract

The aim of this research was to evaluate the potential protective mechanism of astaxanthin (ASTA) against oxidative damage and inflammation caused by ochratoxin (OTA) in mouse lung. We divided mice into a control group (CG), an OTA group (PG), an astaxanthin group (AG), and an OTA+ASTA group (JG). Oxidative indices (malondialdehyde (MDA), total superoxide dismutase (T-SOD), and reduced glutathione (GSH)) and inflammatory markers (interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α)) were assayed in the lung, and the lung-weight-to-body-weight ratio was calculated. Apoptosis was detected in pathological sections by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Oxidative damage and inflammation were detected in the lung of mice after exposure to OTA. Besides, Nrf2- and NF-κB-pathway-associated proteins were detected by Western blot. In contrast with OTA, ASTA significantly raised the expression of Nrf2, HO-1, and MnSOD, while the expression of other proteins (Keap1, TLR4, and NF-κB) was significantly decreased. These results indicate that ASTA exerted protective effects against OTA-induced oxidative damage and inflammation in the lung by regulating the Nrf2 and NF-κB pathways.

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References

Creppy E, Roschenthaler R, DIRHEIMER G . Inhibition of protein synthesis in mice by ochratoxin A and its prevention by phenylalanine. Food Chem Toxicol. 1984; 22(11):883-6. DOI: 10.1016/0278-6915(84)90170-4. View

Okutan H, Aydin G, Ozcelik N . Protective role of melatonin in ochratoxin a toxicity in rat heart and lung. J Appl Toxicol. 2004; 24(6):505-12. DOI: 10.1002/jat.1010. View

Kensler T, Wakabayashi N, Biswal S . Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2006; 47:89-116. DOI: 10.1146/annurev.pharmtox.46.120604.141046. View

Naguib Y . Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000; 48(4):1150-4. DOI: 10.1021/jf991106k. View

Liu D, Su J, Lin J, Qian G, Chen X, Song S . Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo. Int J Biol Macromol. 2018; 120(Pt A):683-692. DOI: 10.1016/j.ijbiomac.2018.08.156. View

Amirshahrokhi K, Khalili A . Carvedilol attenuates paraquat-induced lung injury by inhibition of proinflammatory cytokines, chemokine MCP-1, NF-κB activation and oxidative stress mediators. Cytokine. 2016; 88:144-153. DOI: 10.1016/j.cyto.2016.09.004. View

Skaug M, Eduard W, Stormer F . Ochratoxin A in airborne dust and fungal conidia. Mycopathologia. 2001; 151(2):93-8. DOI: 10.1023/a:1010953401173. View

Krinsky N . Antioxidant functions of carotenoids. Free Radic Biol Med. 1989; 7(6):617-35. DOI: 10.1016/0891-5849(89)90143-3. View

Sava V, Reunova O, Velasquez A, Harbison R, Sanchez-Ramos J . Acute neurotoxic effects of the fungal metabolite ochratoxin-A. Neurotoxicology. 2005; 27(1):82-92. DOI: 10.1016/j.neuro.2005.07.004. View

10.

Chaiprasongsuk A, Janjetovic Z, Kim T, Jarrett S, DOrazio J, Holick M . Protective effects of novel derivatives of vitamin D and lumisterol against UVB-induced damage in human keratinocytes involve activation of Nrf2 and p53 defense mechanisms. Redox Biol. 2019; 24:101206. PMC: 6488822. DOI: 10.1016/j.redox.2019.101206. View

11.

Kim S, Kim H . Inhibitory Effect of Astaxanthin on Oxidative Stress-Induced Mitochondrial Dysfunction-A Mini-Review. Nutrients. 2018; 10(9). PMC: 6165470. DOI: 10.3390/nu10091137. View

12.

Sorrenti V, Di Giacomo C, Acquaviva R, Barbagallo I, Bognanno M, Galvano F . Toxicity of ochratoxin a and its modulation by antioxidants: a review. Toxins (Basel). 2013; 5(10):1742-66. PMC: 3813909. DOI: 10.3390/toxins5101742. View

13.

Lee J, Li J, Johnson D, Stein T, Kraft A, Calkins M . Nrf2, a multi-organ protector?. FASEB J. 2005; 19(9):1061-6. DOI: 10.1096/fj.04-2591hyp. View

14.

Ringot D, Chango A, Schneider Y, Larondelle Y . Toxicokinetics and toxicodynamics of ochratoxin A, an update. Chem Biol Interact. 2005; 159(1):18-46. DOI: 10.1016/j.cbi.2005.10.106. View

15.

Sykiotis G, Habeos I, Samuelson A, Bohmann D . The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation. Curr Opin Clin Nutr Metab Care. 2010; 14(1):41-8. PMC: 3092636. DOI: 10.1097/MCO.0b013e32834136f2. View

16.

Xue X, Han X, Li Y, Chu X, Miao W, Zhang J . Astaxanthin attenuates total body irradiation-induced hematopoietic system injury in mice via inhibition of oxidative stress and apoptosis. Stem Cell Res Ther. 2017; 8(1):7. PMC: 5260077. DOI: 10.1186/s13287-016-0464-3. View

17.

Hope J, Hope B . A review of the diagnosis and treatment of Ochratoxin A inhalational exposure associated with human illness and kidney disease including focal segmental glomerulosclerosis. J Environ Public Health. 2012; 2012:835059. PMC: 3255309. DOI: 10.1155/2012/835059. View

18.

Hibi D, Kijima A, Suzuki Y, Ishii Y, Jin M, Sugita-Konishi Y . Effects of p53 knockout on ochratoxin A-induced genotoxicity in p53-deficient gpt delta mice. Toxicology. 2012; 304:92-9. DOI: 10.1016/j.tox.2012.12.005. View

19.

Gradelet S, Astorg P, Le Bon A, Berges R, Suschetet M . Modulation of aflatoxin B1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids: evidence for a protective effect of CYP1A inducers. Cancer Lett. 1997; 114(1-2):221-3. DOI: 10.1016/s0304-3835(97)04668-5. View

20.

Song X, Wang B, Lin S, Jing L, Mao C, Xu P . Astaxanthin inhibits apoptosis in alveolar epithelial cells type II in vivo and in vitro through the ROS-dependent mitochondrial signalling pathway. J Cell Mol Med. 2014; 18(11):2198-212. PMC: 4224554. DOI: 10.1111/jcmm.12347. View