Skip to main content

Advertisement

Log in

Astaxanthin alleviates gestational diabetes mellitus in mice through suppression of oxidative stress

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Gestational diabetes mellitus (GDM) affects 7% of pregnant women worldwide, which increases the risk of diabetes and cardiovascular disease for both the mother and the fetus. Natural compound Astaxanthin has been reported to have benefits in obesity and diabetes. A pregnant C57BL/KsJ db/+ mouse was used as a genetic GDM model to investigate the effect of Astaxanthin on GDM symptoms and reproductive outcomes. Blood glucose, plasma insulin, glucose intolerance, insulin sensitivity, biochemical indexes of plasma, and the liver were measured; Nrf2 and HO-1 protein levels were detected by Western blotting. Astaxanthin significantly alleviated the glucose intolerance and β cell insufficiency, inhibited in vivo oxidative stress, enhanced the activity of antioxidant enzymes, and improved reproductive outcomes. Mechanistically, the effect of Astaxanthin was mediated by restoring the Nrf2/HO-1 antioxidant pathway in the liver of GDM mice. Our findings supported that Astaxanthin was a potential therapeutic reagent for not only diabetes but also GDM symptomology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Ajmera VH, Gunderson EP, VanWagner LB, Lewis CE, Carr JJ, Terrault NA (2016) Gestational diabetes mellitus is strongly associated with non-alcoholic fatty liver disease. Am J Gastroenterol 111:658–664

    Article  CAS  Google Scholar 

  • Ambati RR, Phang SM, Ravi S, Aswathanarayana RG (2014) Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review. Mar Drugs 12:128–152

    Article  CAS  Google Scholar 

  • American Diabetes A (2004) Gestational diabetes mellitus. Diabetes Care 27(Suppl 1):S88–S90

    Google Scholar 

  • Bloch-Damti A, Bashan N (2005) Proposed mechanisms for the induction of insulin resistance by oxidative stress. Antioxid Redox Signal 7:1553–1567

    Article  CAS  Google Scholar 

  • Buchanan TA (2001) Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab 86:989–993

    Article  CAS  Google Scholar 

  • Buchanan TA, Xiang AH (2005) Gestational diabetes mellitus. J Clin Investig 115:485–491

    Article  CAS  Google Scholar 

  • Castillo-Castrejon M, Powell TL (2017) Placental nutrient transport in gestational diabetic pregnancies. Front Endocrinol (Lausanne) 8:306

    Article  Google Scholar 

  • Catalano PM, Tyzbir ED, Wolfe RR, Roman NM, Amini SB, Sims EA (1992) Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant women. Am J Obstet Gynecol 167:913–919

    Article  CAS  Google Scholar 

  • Catalano PM, Huston L, Amini SB, Kalhan SC (1999) Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol 180:903–916

    Article  CAS  Google Scholar 

  • Chen X, Scholl TO (2005) Oxidative stress: changes in pregnancy and with gestational diabetes mellitus. Curr Diab Rep 5:282–288

    Article  CAS  Google Scholar 

  • Cheng X, Chapple SJ, Patel B, Puszyk W, Sugden D, Yin X, Mayr M, Siow RC, Mann GE (2013) Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero. Diabetes 62:4088–4097

    Article  CAS  Google Scholar 

  • Coughlan MT, Permezel M, Georgiou HM, Rice GE (2004a) Repression of oxidant-induced nuclear factor-kappaB activity mediates placental cytokine responses in gestational diabetes. J Clin Endocrinol Metab 89:3585–3594

    Article  CAS  Google Scholar 

  • Coughlan MT, Vervaart PP, Permezel M, Georgiou HM, Rice GE (2004b) Altered placental oxidative stress status in gestational diabetes mellitus. Placenta 25:78–84

    Article  CAS  Google Scholar 

  • Foghsgaard S, Andreasen C, Vedtofte L, Andersen ES, Bahne E, Strandberg C, Buhl T, Holst JJ, Svare JA, Clausen TD, Mathiesen ER, Damm P, Gluud LL, Knop FK, Vilsboll T (2017) Nonalcoholic fatty liver disease is prevalent in women with prior gestational diabetes mellitus and independently associated with insulin resistance and waist circumference. Diabetes Care 40:109–116

    Article  CAS  Google Scholar 

  • Gao J, Xiao H, Li J, Guo X, Cai W, Li D (2019) N-3 polyunsaturated fatty acids decrease long-term diabetic risk of offspring of gestational diabetes rats by postponing shortening of hepatic telomeres and modulating liver metabolism. Nutrients 11

  • Guo L, Zhang P, Chen Z, Xia H, Li S, Zhang Y, Kobberup S, Zou W, Lin JD (2017) Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression. J Clin Invest 127:4449–4461

    Article  Google Scholar 

  • Hichor M, Sundaram VK, Eid SA, Abdel-Rassoul R, Petit PX, Borderie D, Bastin J, Eid AA, Manuel M, Grenier J, Massaad C (2018) Liver X receptor exerts a protective effect against the oxidative stress in the peripheral nerve. Sci Rep 8:2524

    Article  CAS  Google Scholar 

  • Homko C, Sivan E, Chen X, Reece EA, Boden G (2001) Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab 86:568–573

    PubMed  CAS  Google Scholar 

  • Iwamoto T, Hosoda K, Hirano R, Kurata H, Matsumoto A, Miki W, Kamiyama M, Itakura H, Yamamoto S, Kondo K (2000) Inhibition of low-density lipoprotein oxidation by astaxanthin. J Atheroscler Thromb 7:216–222

    Article  CAS  Google Scholar 

  • Jamilian M, Mirhosseini N, Eslahi M, Bahmani F, Shokrpour M, Chamani M, Asemi Z (2019) The effects of magnesium-zinc-calcium-vitamin D co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes. BMC Pregnancy Childbirth 19:107

    Article  Google Scholar 

  • Kc K, Shakya S, Zhang H (2015) Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab 66(Suppl 2):14–20

    Article  CAS  Google Scholar 

  • Leng J, Li W, Zhang S, Liu H, Wang L, Liu G, Li N, Redman LM, Baccarelli AA, Hou L, Hu G (2015) GDM women’s pre-pregnancy overweight/obesity and gestational weight gain on offspring overweight status. PLoS One 10:e0129536

    Article  CAS  Google Scholar 

  • Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J (2016) Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci 73:3221–3247

    Article  CAS  Google Scholar 

  • McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P (2019) Gestational diabetes mellitus. Nat Rev Dis Primers 5:47

    Article  Google Scholar 

  • Morris JM, Gopaul NK, Endresen MJ, Knight M, Linton EA, Dhir S, Anggard EE, Redman CW (1998) Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia. Br J Obstet Gynaecol 105:1195–1199

    Article  CAS  Google Scholar 

  • Nakao R, Nelson OL, Park JS, Mathison BD, Thompson PA, Chew BP (2010) Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice. Anticancer Res 30:2721–2725

    PubMed  CAS  Google Scholar 

  • Niu T, Xuan R, Jiang L, Wu W, Zhen Z, Song Y, Hong L, Zheng K, Zhang J, Xu Q, Tan Y, Yan X, Chen H (2018) Astaxanthin induces the Nrf2/HO-1 antioxidant pathway in human umbilical vein endothelial cells by generating trace amounts of ROS. J Agric Food Chem 66:1551–1559

    Article  CAS  Google Scholar 

  • Park JS, Chyun JH, Kim YK, Line LL, Chew BP (2010) Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond) 7:18

    Article  CAS  Google Scholar 

  • Peuchant E, Brun JL, Rigalleau V, Dubourg L, Thomas MJ, Daniel JY, Leng JJ, Gin H (2004) Oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes. Clin Biochem 37:293–298

    Article  CAS  Google Scholar 

  • Sila A, Ghlissi Z, Kamoun Z, Makni M, Nasri M, Bougatef A, Sahnoun Z (2015) Astaxanthin from shrimp by-products ameliorates nephropathy in diabetic rats. Eur J Nutr 54:301–307

    Article  CAS  Google Scholar 

  • Sireesh D, Dhamodharan U, Ezhilarasi K, Vijay V, Ramkumar KM (2018) Association of NF-E2 related factor 2 (Nrf2) and inflammatory cytokines in recent onset type 2 diabetes mellitus. Sci Rep 8:5126

    Article  CAS  Google Scholar 

  • Song H, Xu Y, Yang X, Rong X, Wang Y, Wei N (2019) Tertiary butylhydroquinone alleviates gestational diabetes mellitus in C57BL/KsJ-Lep db/+ mice by suppression of oxidative stress. J Cell Biochem 120:15310–15319

    Article  CAS  Google Scholar 

  • Suman RK, Mohanty IR, Maheshwari U, Borde MK, Deshmukh YA (2016) Natural dipeptidyl peptidase-IV inhibitor mangiferin mitigates diabetes- and metabolic syndrome-induced changes in experimental rats. Diabetes Metab Syndr Obes 9:261–272

    Article  CAS  Google Scholar 

  • Toescu V, Nuttall SL, Martin U, Kendall MJ, Dunne F (2002) Oxidative stress and normal pregnancy. Clin Endocrinol 57:609–613

    Article  CAS  Google Scholar 

  • Uchiyama K, Naito Y, Hasegawa G, Nakamura N, Takahashi J, Yoshikawa T (2002) Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep 7:290–293

    Article  CAS  Google Scholar 

  • Whyte K, Kelly H, O’Dwyer V, Gibbs M, O’Higgins A, Turner MJ (2013) Offspring birth weight and maternal fasting lipids in women screened for gestational diabetes mellitus (GDM). Eur J Obstet Gynecol Reprod Biol 170:67–70

    Article  CAS  Google Scholar 

  • Xiang AH, Wang X, Martinez MP, Getahun D, Page KA, Buchanan TA, Feldman K (2018) Maternal gestational diabetes mellitus, type 1 diabetes, and type 2 diabetes during pregnancy and risk of ADHD in offspring. Diabetes Care 41:2502–2508

    Article  CAS  Google Scholar 

  • Yamashita H, Shao J, Ishizuka T, Klepcyk PJ, Muhlenkamp P, Qiao L, Hoggard N, Friedman JE (2001) Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth. Endocrinology 142:2888–2897

    Article  CAS  Google Scholar 

  • Ying CJ, Zhang F, Zhou XY, Hu XT, Chen J, Wen XR, Sun Y, Zheng KY, Tang RX, Song YJ (2015) Anti-inflammatory effect of Astaxanthin on the sickness behavior induced by diabetes mellitus. Cell Mol Neurobiol 35:1027–1037

    Article  CAS  Google Scholar 

  • Zhang C, Williams MA, Sorensen TK, King IB, Kestin MM, Thompson ML, Leisenring WM, Dashow EE, Luthy DA (2004) Maternal plasma ascorbic acid (vitamin C) and risk of gestational diabetes mellitus. Epidemiology 15:597–604

    Article  Google Scholar 

  • Zhao W, Zhang L, Zhang G, Varkaneh HK, Rahmani J, Clark C, Ryan PM, Abdulazeem HM, Salehisahlabadi A (2019) The association of plasma levels of liver enzymes and risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis of observational studies. Acta Diabetol

Download references

Funding

This study was funded by the Project of Yantai City, grant number: 2018SFGY101.

Author information

Authors and Affiliations

Authors

Contributions

Yangyang Chen, Jichun Tang, and Yinghong Zhang conceptualized the study and conducted the literature review for all databases. Juan Du, Yuanli Wang, and Hui Yu performed all statistical analyses. Yanling He drafted the paper. Yanling He provided useful additional intellectual content into the draft and contributed to the writing of the final version of the paper. The experiments were performed in-house, and no paper mill was used.

Corresponding author

Correspondence to Yanling He.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 87 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Tang, J., Zhang, Y. et al. Astaxanthin alleviates gestational diabetes mellitus in mice through suppression of oxidative stress. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2517–2527 (2020). https://doi.org/10.1007/s00210-020-01861-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-020-01861-x

Keywords

Navigation