Is it possible to antagonize 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin- induced cleft palate by prenatal administration of folic acid? An experimental study.
ABSTRACT 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can cause a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including C57BL/6J. In this study, folic acid (FA) was tested for antiteratogenic effects on TCDD-induced cleft palate in fetal mice. The pregnant C57BL/6J mice were dosed with 24 microg TCDD/kg and/or 5 mg, 10 mg, 20 mg, 40 mg FA/kg body weight on gestation day (GD) 10. The control group mice received 50 mL sesame oil/kg body weight on GD10. The mice were sacrificed on GD12.5, GD13.5, GD14.5, GD15.5, and GD16.5. The harvested embryos were examined to detect the incidence of cleft palate and the developing palatal shelves on different phases were investigated morphologically and histologically among different groups. Total frequency of clefts was 55.56% in TCDD group and 17.50% (5 mg), 42.85% (10 mg), 42.10% (20 mg), 28.26% (40 mg) in TCDD + FA groups. FA (5 mg) reduced the incidence of the cleft palate from 55.56% to 17.50% (p = 0.005). There were no significant differences between the TCDD group and 10 mg, 20 mg, 40 mg TCDD + FA groups. Based on the these results, the present study suggests that FA can reduce the incidence of 2,3,7,8-TCDD-induced cleft palate in mice.
- [Show abstract] [Hide abstract]
ABSTRACT: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that leads to the development of hepatotoxicity. Docosahexaenoic acid (DHA) has been proposed to counteract oxidative stress and improve antioxidant status, and several studies suggest that supplementations with antioxidants can influence hepatotoxicity. The aim of the current study was to explore the role of DHA in modulating the toxicity of TCDD in the liver of Sprague-Dawley rats. Animals were assigned to four groups (n = 5): control (only dimethyl sulfoxide (DMSO)), 8 μg/kg body weight (b.w.) TCDD in DMSO solution; 250 mg/kg b.w. DHA and TCDD plus DHA; respectively. Rats were intraperitoneally administered their respective doses daily for 21 days. On day 21, the animals were killed, and then biochemical tests, pathological examination, and micronucleus (MN) assay were performed in the liver. Our results showed that the activities of antioxidant enzymes were significantly decreased and serious pathological findings were established in rats that received TCDD. Beside the rate of MNs in hepatocytes was increased after the treatment with dioxin. In rats treated with DHA alone, MNs were not changed and the activities of antioxidant enzymes were significantly increased. The presence of DHA with TCDD alleviated its pathological effects in hepatic tissue. DHA also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. It can be concluded that DHA has beneficial influences and could be able to antagonize TCDD toxicity in liver.Toxicology and Industrial Health 10/2011; 28(8):687-96. · 1.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to explore the effectiveness of L-glutamine (Gln) in alleviating the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in liver of rats. Rats were intraperitoneally administered Gln and TCDD doses daily for 21 days. In the liver of rats, the biochemical tests, pathological examination and micronucleus (MN) test were performed. TCDD significantly decreased the activities of antioxidant enzymes and serious pathological findings. Moreover, the rate of MNs in hepatocytes increased after treatment with dioxin. In rats treated with Gln alone, the MNs remained unchanged, but the ratio of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) were significantly increased. Gln also prevented the suppression of GSH-Px (except for superoxide dismutase and catalase) and GSH in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. Thus, our findings for Gln might provide new insight into the development of therapeutic and preventive approaches in TCDD toxicity.Toxicology and Industrial Health 10/2011; 28(7):663-72. · 1.71 Impact Factor