The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver

Philip A. Kern, Renata B. Fishman, Wei Song, Aliza Dicker Brown, Vivian Fonseca

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Reactive oxygen species are produced in response to environmental toxins, and previous studies have suggested that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) damages a number of target organs through the generation of oxygen free radicals and oxidative stress. Upon exposure, TCDD becomes concentrated in adipose tissue, and adversely affects many organs, including liver. This study examined whether oxidative stress was induced in adipocytes and liver that were exposed to TCDD. 3T3-F442A adipocyte cultures were treated with TCDD (5-200 nM) for up to 72 h, and the activity and mRNA levels of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) in adipocyte cell lysates were measured. The addition of 50 nM TCDD induced a two-fold increase in SOD activity after 48 h (P<0.05). In contrast, TCDD had no significant effect on the activity of catalase or GSH-Px in the adipocytes, and the increase in SOD activity was not accompanied by a change in SOD mRNA levels. To assess the effects of TCDD on oxidative stress enzymes in vivo, male Sprague-Dawley rats were injected weekly for 8 weeks with 30 ng/kg TCDD. In addition, the rats were fed either a low-fat complex-carbohydrate (LFCC) diet, or a high fat sucrose diet (HFS). The HFS diet has previously been shown to induce mild obesity and insulin resistance, without inducing diabetes. SOD, catalase, and GSH-Px activities were measured in the liver and adipose tissue of these rats. TCDD injection resulted in a 52% decrease in catalase activity in the adipose tissue of HFS rats (P<0.05). In contrast, SOD and GSH-Px activities were not altered in adipose tissue of TCDD-injected rats. In liver, however, there were significant decreases in GSH-Px activity in response to TCDD. This effect of TCDD was observed in both the LFCC and HFS dietary groups. In addition, GSH-Px activity in the HFS rats was significantly decreased when compared to GSH-Px activity in LFCC rats, in both TCDD-treated and control groups, suggesting that TCDD and a high fat diet may combine to exacerbate oxidative stress. Thus, TCDD induces complex changes in enzymes of oxidative stress in both adipocytes and liver. In adipocytes, these changes occurred post-transcriptionally, as there were no changes in mRNA levels. In addition, a high fat diet per se also resulted in a decrease in GSH-Px activity in liver.

Original languageEnglish
Pages (from-to)117-125
Number of pages9
JournalToxicology
Volume171
Issue number2-3
DOIs
StatePublished - Feb 28 2002
Externally publishedYes

Fingerprint

Adipocytes
Liver
Nutrition
Enzymes
High Fat Diet
Fats
Rats
Oxidative stress
Superoxide Dismutase
Sucrose
Oxidative Stress
Catalase
Adipose Tissue
Tissue
Carbohydrates
1,4-dioxin
Polychlorinated Dibenzodioxins
Messenger RNA
Reactive Oxygen Species
Dietary Sucrose

Keywords

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin
  • Adipocytes and liver
  • High fat diet
  • Oxidative enzymes

ASJC Scopus subject areas

  • Toxicology

Cite this

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver. / Kern, Philip A.; Fishman, Renata B.; Song, Wei; Brown, Aliza Dicker; Fonseca, Vivian.

In: Toxicology, Vol. 171, No. 2-3, 28.02.2002, p. 117-125.

Research output: Contribution to journalArticle

Kern, Philip A. ; Fishman, Renata B. ; Song, Wei ; Brown, Aliza Dicker ; Fonseca, Vivian. / The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver. In: Toxicology. 2002 ; Vol. 171, No. 2-3. pp. 117-125.
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