Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls

Abstract

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μ mol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPARα, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.

Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

“…Recent studies have demonstrated PCBs’ interaction with other nuclear receptors including human PXR and rodent peroxisome-proliferator activated receptor alpha (PPARα) (Al-Salman and Plant, 2012; Robertson et al, 2007; Wahlang et al, 2014). We hypothesized that Aroclor 1260 may interact with these receptors in our animal model.…”

Acute toxicity of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) in male Sprague–Dawley rats: Effects on hepatic oxidative stress, glutathione and metals status

“…This reduction in hepatic SeGPx activity may increase oxidative stress by reducing the liver’s capacity to remove hydrogen peroxide. In a separate study we found that PCB 126 also suppresses hepatic catalase activity, further diminishing the liver’s ability to remove hydrogen peroxide (Robertson et al 2007). The PCB 126-induced decrease in total GPx activity, which consists of both SeGPx and glutathione transferase (GST) activities, was diminished, but at a lower magnitude to that of SeGPx, suggesting an induction of GST (Prohaska 1980; Schramm et al 1985).…”

Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

“…For peroxisome proliferator activated receptors (PPARs) Ariyoshi et al (1998) and Robertson et al (2007) found that the highly toxic more co-planar PCB 126 acts as inverse agonist and reduces liver peroxisomal enzyme activity in the rat model. Other co-planar meta-and parasubstituted PCBs should have the same potential (Ludewig et al, 2007).…”