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

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 quercetinon gestation days (GD) 4-7. At GD 9, all rats were euthanized, and their blood, liver, and uterus were collected. Expressions of CYP 450 mRNA and protein in liver, cytokines (IFNc, IL-2, IL-4, and IL-6) and IFNc/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 IFNc, IL-2, IL-6, and IFNc/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.

Upregulation of CCL7, CCL20, CXCL2, IL-1β, IL-6 and MMP-9 in Skin Samples of PCB Exposed Individuals—A Preliminary Study

“…We found an upregulation of IL-6 in skin biopsies of PCB exposed workers. In agreement with our study, increased IL-6 levels (together with IFNγ, Il-2, and IFNγ/IL-4 ratios) were found in livers and serum of PCB (Aroclor 1254) treated rats [36]. An upregulation of IL-6 has been reported in several kinds of malignancies, and works as a tumor promotor in the tumor microenvironment through multiple pathways including the NF-kB and MAPK/ERK signaling pathway, including promotion of proliferation, angiogenesis and invasiveness [37].…”

The influence of sex, genotype, and dose on serum and hippocampal cytokine levels in juvenile mice developmentally exposed to a human-relevant mixture of polychlorinated biphenyls

“…Rodent models of PCB exposure demonstrate altered cytokines in maternal serum ( Xu et al, 2019 ) as well as fetal brain tissue and serum following gestational exposure to legacy PCB congeners or mixtures. Increased concentrations of inflammatory cytokines TNF-α, interleukin-1β (IL-1β), and interferon-gamma (IFN-γ) were observed in fetal serum following developmental exposure of rats to the coplanar (dioxin-like) congener PCB 126 ( Ahmed et al, 2018 ).…”

Gene × environment interactions in autism spectrum disorders

“…Rodent studies further strengthen the association of PCBs with altered immune/inflammation responses. In pregnant rats, exposure to Aroclor 1254 increased expression of IL-6, IFNγ and IL-2 in liver and serum (Xu, Guo, Li, Pan, & Ma, 2019). In another rat study, developmental exposure to PCB 126 via the dam increased ILl-1B and IFNγ in the serum of offspring (Ahmed, El-Gareib, & Shaker, 2018).…”