Effects of quercetin on Aroclor 1254-induced expression of CYP450 and cytokines in pregnant rats

J Immunotoxicol. 2019 Dec;16(1):140-148. doi: 10.1080/1547691X.2019.1604585.

Abstract

The present study aimed to investigate the protective effect of quercetin on polychlorinated biphenyls (PCB)-induced liver and embryo damage in pregnant Sprague-Dawley rats. Pregnant rats were divided into five groups, and then were orally gavaged daily with peanut oil (vehicle) or a commercial PCB mixture (Aroclor 1254) - with or without co-treatment with 75, 150, or 300 mg/kg quercetin - on gestation days (GD) 4-7. At GD 9, all rats were euthanized, and their blood, liver, and uterus were collected. Expressions of CYP450 mRNA and protein in liver, cytokines (IFNγ, IL-2, IL-4, and IL-6) and IFNγ/IL-4 ratios in liver and sera, liver morphology, and the status of implanted embryos were analyzed. The results showed Aroclor 1254 treatment alone caused hepatic cord damage (i.e. cell disorganization, swelling, decreased cytoplasm, vacuolization), and that quercetin co-treatment appeared to mitigate this damage. Similarly, levels of CYP1A1 and CYP2B1 mRNA in livers of Aroclor 1254-only-treated rats were significantly higher than those in rats co-treated with quercetin. Hepatic and sera levels of IFNγ, IL-2, IL-6, and IFNγ/IL-4 ratios, and the ratio of delayed-development embryos, all increased in Aroclor 1254-treated rats, but were relatively decreased as a result of quercetin co-treatments. IL-4 levels were decreased by Aroclor 1254 and tended to increase back to normal when quercetin was used. The results indicated that quercetin imparted a protective effect against Aroclor 1254-induced toxicity in pregnant rats, in part, by modulating levels of important pro-inflammatory cytokines and reducing induced CYP1A1 and CYP2B1 expression.

Keywords: Aroclor 1254; CYP; IFNγ/IL-4; Quercetin; cytokines; embryo; liver; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Chlorodiphenyl (54% Chlorine) / toxicity*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP2B1 / metabolism
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Embryo, Mammalian / drug effects
  • Embryo, Mammalian / metabolism
  • Female
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Pregnancy
  • Prenatal Injuries / blood
  • Prenatal Injuries / chemically induced
  • Prenatal Injuries / metabolism
  • Prenatal Injuries / prevention & control*
  • Quercetin / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

Substances

  • Antioxidants
  • Cytokines
  • Chlorodiphenyl (54% Chlorine)
  • Quercetin
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1