Exposure to polychlorinated biphenyls enhances lipid peroxidation in human normal peritoneal and adhesion fibroblasts: A potential role for myeloperoxidase

Abstract

Nitric oxide (NO), superoxide and lipid peroxidation (LPO) produced under oxidative stress may contribute to development of postoperative adhesions. The objective of this study was to determine the effects of polychlorinated biphenyls (PCBs) on LPO, superoxide dismutase (SOD3), myeloperoxidase (MPO), and nitrite/nitrate in human normal peritoneal and adhesion fibroblasts. PCB treatment reduced iNOS expression as well as levels of nitrite/nitrate in both cell lines. Although there was no difference in iNOS expression between the two cell lines, adhesion fibroblasts manifested lower basal levels of MPO as compared to normal peritoneal fibroblasts. There was a reduction in MPO expression and its activity in response to PCB treatment in normal peritoneal fibroblasts; however this effect was minimal in adhesion fibroblasts. Moreover, adhesion fibroblasts manifested higher levels of LPO as compared to normal peritoneal fibroblasts, whereas PCB treatment increased LPO levels in both cell types. We conclude that PCBs promote the development of the adhesion phenotype by generating an oxidative stress environment. This is evident by lower iNOS, MPO, nitrite/nitrate and the simultaneous increase in LPO. Loss of MPO activity, possibly through a mechanism involving MPO heme depletion and free iron release, is yet another source of oxidative stress.

Developmental toxicity, oxidative stress, and related gene expression induced by dioxin-like PCB 126 in zebrafish (Danio rerio)

“…Persistent oxidative stress may produce an imbalance between the oxidants and antioxidants, which can lead to potential cell damage, toxicity, and related pathophysiological effects caused by increased production of ROS, lipid peroxidation and DNA damage (Covarrubias et al, ; Lassen et al, ). Several toxic effects induced by TCDD and PCBs are related to oxidative stress since these chemicals can alter the antioxidant defense system in a variety of tissues in several mammalian species (Hassoun et al, ; Jin et al, ; Park and Rho, ; Saed et al, ) including the rat but very little is known in fish species. The antioxidant system includes in addition to the antioxidant enzymes Sod, Gpx, Cat, several nonenzyme antioxidants such as glutathione (GSH), vitamins A, C, and E (Schlezinger et al, ).…”

“…The antioxidant enzymatic protection against ROS include superoxide dismutase (Sod), catalase (Cat), glutathione‐ S ‐transferase (Gst), and glutathione peroxidase (Gpx) enzymes (Lassen et al, ). Acute doses of TCDD or PCBs cause lipid peroxidation and significant oxidative damage to peritoneal and adhesion fibroblasts in the human (Saed et al, ) testicular and Sertoli cell (Krishnamoorthy et al, ). Twaroski et al () demonstrated that PCB77 decreased hepatic Gpx activity and Gpx1 messenger RNA (mRNA) gene expression in rats.…”

Effects of hypoxia on the expression of inflammatory markers IL-6 and TNF-a in human normal peritoneal and adhesion fibroblasts

“…Understanding how TNF-α and IL-6 function at the site of peritoneal injury and what factors modulate its activity will help delineate the mechanism of postoperative adhesion development, thereby revealing new pathways for pharmacological and/or biological modulation. Based on prior extensive studies characterizing the adhesion phenotype, and in view of these observations, we now hypothesize that hypoxia modulates TNF-α and IL-6 expression in normal peritoneal fibroblasts, thereby creating an inflammatory-like milieu, which in part contributes to postoperative adhesion [Alpay et al 2008;Awonuga et al 2009;Fletcher et al 2008;Jiang et al 2008;Saed and Diamond 2006;Saed et al 2009;Saed et al 2008b;Saed et al 2010]. In support of this hypothesis, it was recently found that acute inflammation in the mouse peritoneal cavity was associated with increased incidence and severity of adhesion development [Corona et al 2011].…”

Nicotinamide Adenine Dinucleotide Phosphate Oxidase Expression Is Differentially Regulated to Favor a Pro-oxidant State That Contributes to Postoperative Adhesion Development

“…8 Adhesion fibroblasts manifest an altered redox balance that includes decreased myeloperoxidase, superoxide dismutase (SOD), caspase-3 activity, nitrate/nitrite, S-nitrosylation of caspase-3, and lipid peroxidation as compared to normal peritoneal fibroblasts. 26 –28 Indeed, scavenging O 2 •− , by SOD, restores the adhesion phenotype markers, TGF-β1 and type I collagen, levels in adhesion fibroblasts to the levels observed in normal peritoneal fibroblasts. 8 Furthermore, during hypoxia exposure scavenging O 2 •− protected against the development of adhesion phenotype.…”