Production of superoxide anion, lipid peroxidation and DNA damage in the hepatic and brain tissues of rats after subchronic exposure to mixtures of TCDD and its congeners

Abstract

In this study the induction of oxidative stress in the hepatic and brain tissues of rats after subchronic exposure to various mixtures of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and two of its congeners, namely 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was investigated. Four mixtures of TCDD and its congeners, corresponding to 10, 22, 46 and 100 ng of toxic equivalence (TEQ) kg(-1) day(-1), were administered to groups of rats for 13 weeks. The animals were sacrificed at the end of the exposure period and the biomarkers of oxidative stress, including the production of superoxide anion, lipid peroxidation and DNA single-strand breaks (SSBs), were determined in the hepatic and brain tissues. All mixtures caused dose-dependent increases in the production of superoxide anion, lipid peroxidation and DNA SSBs in both tissues, with significantly higher damage in the hepatic compared with the brain tissues. The 22 ng TEQ dose level (TEQ = 22) contains TCDD, PeCDF and PCB 126 at levels that correspond to 7.3, 14.5 and 73.3 ng kg(-1) day(-1), respectively, and it produced effects that correspond to ca. 50% of the maximal production of superoxide anion, lipid peroxidation and DNA SSBs in the hepatic and brain tissues of those animals. Relative to the doses that are required to produce 50% of the maximal production of the biomarkers of oxidative stress by the individual congeners in hepatic and brain tissues of rats, the concentrations of the congeners in TEQ = 22 did result in significant interactivity, probably in the form of additive effects in the hepatic but not in brain tissues.

Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes

“…TCDD-induced oxidative stress causes 8-OH-dG and single strand breaks in DNA from liver and brain tissues of rats (Hassoun et al 2000;Hassoun et al 2001). In our study, 8-OH-dG significantly increases by the effect of TCDD.…”

Olfactory Epithelial Metaplasia and Hyperplasia in Female Harlan Sprague–Dawley Rats Following Chronic Treatment with Polychlorinated Biphenyls

“…With respect to this it should be noted that TCDD and related DLCs are not direct acting genotoxic agents. However they do have the ability to induce oxidative stress and hepatic oxidative DNA damage after prolonged exposure (Hassoun et al, 2000(Hassoun et al, , 2001Wyde et al, 2004).…”

Clinical and Experimental Applications of NIR-LED Photobiomodulation

“…[35][36][37] Further, dioxin has long been known to induce cellular oxidative stress and increase production of free radicals. 38 It is through a combination of these mechanisms that dioxin and the PHAHs are believed to increase the incidence of birth defects, and a variety of cancers and hormonally linked dysfunctions in humans and wildlife. In addition, late embryo mortality, which is typical of birds exposed to higher levels of dioxin, has long been hypothesized to be due to cellular stress decreasing available energy needed for the animal to peck out of the shell.…”