The protective effect of quercetin in the alcohol-induced liver and lymphoid tissue injuries in newborns

  • Erdal InceEmail author
Original Article


Recently published experimental and clinical studies indicate that oxidative stress leads to the pathogenesis and progression of alcohol-induced tissue injuries. Quercetin is a type of flavonoid compound that influences antioxidant and anti-inflammatory activities have protective and therapeutic effects for treating various diseases including diabetes mellitus and neuro-degenerative diseases. In this study, fetal alcohol syndrome was tested in rat models, with the aim of verifying the protective effect of quercetin in preventing alcohol-induced liver and lymphoid tissue (thymus, spleen, and lymph nodes) injuries on the 21st day for the offspring of alcohol treated mother rats. The pregnant rats were randomly assigned into four groups. The control group (C) (n = 3) of pregnant rats received only physiological saline intraperitoneally (i.p.) throughout the pregnancy (1 to 21 days gestation) and during lactation until postnatal day 21. The quercetin positive control group (QT) of pregnant rats (n = 3) received quercetin at 50 mg/kg/days i.p. for the same period. The ethanol treatment group (E) (n = 3) of pregnant rats received 1 ml/day of 40% v/v ethanol (4 g/kg) intragastrically (i.g) for the same period. The model group of pregnant rats (EQ) received ethanol + quercetin (n = 3) with a dose of 1 ml/day of v/v ethanol (4 g/kg i.g.) and quercetin at 50 mg/kg body weight per day i.p. for the same period. Ten offspring were used in each of the C, QT, E and EQ groups. Malondialdehyde (MDA), protein carbonyl content (PC) and chemiluminescence levels (CL) in liver and lymphoid tissues significantly increased in group E versus the C group (P < 0.05–P < 0.001) whereas glutathione levels (GSH), glutathione reductase (GR), glutathione peroxidase (GP), superoxide dismutase (SOD), and catalase (CAT) activities significantly decreased in group E compared to the C group (P < 0.05–< 0.001). However, tissue MDA, PC, and CL levels decreased in the EQ group compared to group E. GSH level, GP, GR, SOD, and CAT activity were significantly increased by quercetin (P < 0.05–P < 0.001). The plasma TNFα, IL-1β, and IL-6 levels and NF-κB activation significantly increased in group E compared to the C and QT groups, but IL-10 significantly decreased in group E compared to the C and QT groups. The TNFα, IL-1β, and IL-6 levels and NF-κB activation significantly decreased in group EQ compared to group E. In conclusion, quercetin has a protective effect against maternal alcohol-induced oxidative and inflammatory damage in the liver and lymphoid tissues of newborn rats.


Maternal alcohol Oxidative stress Quercetin Inflammatory responses Lymphoid tissues 



Fetal alcohol spectrum disorder


Reactive oxygen species


Lipid peroxidation


Protein carbonyl content


Chemiluminescence assay


Reduced glutathione


Glutathione peroxidase


Glutathione reductase


Superoxide dismutase






Nuclear factor kappa B


Proinflammatory cytokine


Compliance with ethical standards

Conflict of interest

The author has no financial or any other conflict of interest in this manuscript with third parties. The author is responsible for the content and writing of this paper.


  1. 1.
    Akhtar F, Rouse CA, Catano G, Montalvo M et al (2017) Acute maternal oxidant exposure causes susceptibility of the fetal brain to inflammation and oxidative stress. J Neuroinflammation 14:195CrossRefGoogle Scholar
  2. 2.
    Goodlett CR, Horn KH (2001) Mechanisms of alcohol-induced damage to the developing nervous system. Alcohol Res Health 25(3):175–184PubMedPubMedCentralGoogle Scholar
  3. 3.
    Williams JF, Smith VC (2015) Committee on substance abuse a fetal alcohol spectrum disorders. Pediatrics 136(5):e1395CrossRefGoogle Scholar
  4. 4.
    Barr HM, Streissguth AP (2001) Identifying maternal self-reported alcohol use associated with fetal alcohol spectrum disorders. Alcohol Clin Exp Res 25:283–287CrossRefGoogle Scholar
  5. 5.
    Marino MD, Aksenov MY, Kelly SJ (2004) Vitamin E protects against alcohol-induced cell loss and oxidative stress in the neonatal rat hippocampus. Int J Dev Neurosci 22:363–377CrossRefGoogle Scholar
  6. 6.
    Amini SA, Dunstan H, Raymond P, Murdoch PDR (1996) Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy. Free Radical Biol Med 21(3):357–365. CrossRefGoogle Scholar
  7. 7.
    Aydın B (2011) Effects of thiacloprid, deltamethrin and their combination on oxidative stress in lymphoid organs, polymorphonuclear leukocytes and plasma of rats. Pestic Biochem Physiol 100:65–171CrossRefGoogle Scholar
  8. 8.
    Sibley D, Jerrells TR (2000) Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid cells from the Gut-associated lymphoid tissues and altered resistance to oral infections with Salmonella typhimuriu. J Infect Dis 182:482–489CrossRefGoogle Scholar
  9. 9.
    Walia AS, Pruitt KM, Rodgers JD, Lamon EW (1987) In vitro effect of ethanol on cell-mediated cytotoxicity by murine spleen cells. Immunopharmacology 13(1):11–210CrossRefGoogle Scholar
  10. 10.
    İnce E, Curabeyoğlu F, Akyol S (2019) Oxidative stress in lymphoid tissues and complement activation in alcoholic mother rats and their newborns. General Biophys Physiol 38(1):91–100CrossRefGoogle Scholar
  11. 11.
    Bodnar T, Hill LA, Weinberg J (2016) Evidence for an immune signature of prenatal alcohol exposure in female rats. Brain Behav Immun 58:130–141CrossRefGoogle Scholar
  12. 12.
    Zhu M, Zhou X, Zhao J (2017) Quercetin prevents alcohol-induced liver injury through targeting of PI3 K/Akt/Nuclear Factor-κB and STAT3 signaling pathway. Exp Ther Med 14:6169–6175PubMedPubMedCentralGoogle Scholar
  13. 13.
    Li X, Jin Q, Yao Q, Xu B, Li L et al (2018) The Flavonoid Quercetin ameliorates liver inflammation and fibrosis by regulating hepatic macrophages activation and polarization in mice. Front Pharmacol 9:72. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vanhees K, Godschalk RW, Sanders A et al (2011) Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood. Toxicology 290(2–3):350–358CrossRefGoogle Scholar
  15. 15.
    Romaszko E, Wiczkowski W, Romaszko J et al (2014) Exposure of breastfed infants to quercetin after consumption of a single meal rich in quercetin by their mothers. Mol Nutr Food Res 58(2):221–228CrossRefGoogle Scholar
  16. 16.
    Lundquist F (1959) The determination of ethyl alcohol in blood and tissues. In: Glick D (ed) Methods of biochemical analysis. Interscience Publishers Inc, New York, p 217Google Scholar
  17. 17.
    Singh RP, Padmavathi B, Rao R (2000) Modulatory influence of Adhatoda vesicaleaf extract on the enzymes of xenobiotic metabolism, antioxidant status and lipid peroxidation in mice. Mol Cell Biochem 213:9–109CrossRefGoogle Scholar
  18. 18.
    Levine RL, Williams JA, Stadtman ER et al (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 233:346–357CrossRefGoogle Scholar
  19. 19.
    Davies GR, Simmonds NJ, Stevens TRJ et al (1992) Mucosal reactive oxygen metabolite production in duodenal ulcer disease. Gut 33:1467–1472CrossRefGoogle Scholar
  20. 20.
    Ohara Y, Peterson TE, Harrison DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91:2546–2551CrossRefGoogle Scholar
  21. 21.
    Haklar G, Yüksel M, Yalçın AS (1998) Chemiluminescence in the measurement of free radicals: theory and application on a tissue injury model. Marmara Med. J 11:56–60Google Scholar
  22. 22.
    Carlberg I, Mannervik B (1981) Purification and characterization of glutathione reductase from calf liver glutathione reductase assays. Methods Enzymol 113:484–495CrossRefGoogle Scholar
  23. 23.
    Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMedGoogle Scholar
  24. 24.
    Carlberg I, Mannervik B (1981) Purification and characterization of glutathione reductase from calf liver glutathione reductase assays. Methods Enzymol 113:484–495CrossRefGoogle Scholar
  25. 25.
    Sun Y, Oberley LW, Li Y (1998) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500Google Scholar
  26. 26.
    Aebi H (1985) Catalase. Methods EnzymolGoogle Scholar
  27. 27.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefGoogle Scholar
  28. 28.
    Molina PE, Hoek JB, Nelson S, Guidot DM, Lang CH et al (2003) Mechanisms of alcohol-induced tissue injury. Alcohol Clin Exp Res 27:563–575CrossRefGoogle Scholar
  29. 29.
    Wu D, Cederbaum AI (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 27(4):277–284PubMedPubMedCentralGoogle Scholar
  30. 30.
    Wu CH, Chen CC, Lai CY, Hung TH, Lin CC et al (2016) Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage. J Neuroinflammation 13:62CrossRefGoogle Scholar
  31. 31.
    Kahraman A, Cakar H, Koken T (2012) The protective effect of quercetin on long-term alcohol consumption-induced oxidative stress. Mol Biol Rep 39:2789–2794CrossRefGoogle Scholar
  32. 32.
    Ambade A, Mandrekar P (2012) Oxidative stress and inflammation: essential partners in alcoholic liver disease. Int J Hepatol. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Coll TA, Chaufan G, Pérez-Tito LG et al (2018) Cellular and molecular oxidative stress-related effects in uterine myometrial and trophoblast-decidual tissues after perigestational alcohol intake up to early mouse organogenesis. Mol Cell Biochem 440(1–2):89–104CrossRefGoogle Scholar
  34. 34.
    Movileanu L, Neagoe I, Flonta ML (2000) Interaction of the antioxidant flavonoid quercetin with planar lipid bilayers. Int J Pharm 205(1–2):135–146CrossRefGoogle Scholar
  35. 35.
    Vanhees K, Godschalk RW, Sanders A et al (2011) Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood. Toxicology 290(2–3):350–358CrossRefGoogle Scholar
  36. 36.
    Afasenev IB, Dcrozhko A, Brodski AV et al (1989) Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochem Biopharmacol 38(11):1763–1769CrossRefGoogle Scholar
  37. 37.
    Cederbaum AI, Lu Y, Wu D (2009) Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol 83:519–548CrossRefGoogle Scholar
  38. 38.
    Ding RB, Tian K, Cao YW et al (2015) Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress. J Agric Food Chem 63:2413–2422CrossRefGoogle Scholar
  39. 39.
    Choi EJ, Chee KM, Lee BH (2003) Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol 482(1–3):281–285CrossRefGoogle Scholar
  40. 40.
    Tong M, Longato L, Ramirez T et al (2014) Therapeutic reversal of chronic alcohol-related steatohepatitis with the ceramide inhibitor myriocin. Int J Exp Pathol 95(1):49–63CrossRefGoogle Scholar
  41. 41.
    Chen L, Deng H, Cui H, Fang J, Zuo Z et al (2018) Inflammatory responses and inflammation associated diseases in organs. Oncotarget 9(6):7204–7218PubMedGoogle Scholar
  42. 42.
    Burd L, Blair J, Dropps K (2012) Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn. J Perinatol 32:652–659CrossRefGoogle Scholar
  43. 43.
    Tan Z, Luo M, Yang J et al (2016) Chlorogenic acid inhibits cholestatic liver injury induced by α-naphthylisothiocyanate: involvement of STAT3 and NFκB signalling regulation. J Pharm Pharmacol 68:1203–1213CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Medical Science Biology, Cerrahpasa Medical FacultyIstanbul University—CerrahpasaFatih/IstanbulTurkey

Personalised recommendations