Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice
Introduction
Occupational exposure to structurally diverse environmental toxicants including heavy metals and polyhalogenated and/or polycyclic aromatic hydrocarbons may involve a common cascade of events which includes the production of reactive oxygen species (ROS) and an oxidative stress leading to lipid (Bagchi et al., 1997b, Stohs and Bagchi, 1995), DNA damage (Bagchi et al., 1995a, Bagchi et al., 1995b, Bagchi et al., 1995c, Bagchi et al., 1997a, Bagchi et al., 1998c, Bagchi et al., 1998, Hassoun et al., 1993), membrane damage with decreased membrane fluidity (Bagchi et al., 1992), apoptosis (Bagchi et al., 1998a), glutathione depletion (Bagchi et al., 1996a, Bagchi et al., 1996b, Stohs and Bagchi, 1995, Stohs, 1990), altered calcium homeostasis (Bagchi et al., 1997a, Stohs, 1990), activation of protein kinase C (Bagchi et al., 1997a), enhanced release of tumor necrosis factor alpha (Stohs and Bagchi, 1995, Stohs, 1990), induction of stress/heat shock protein 90 (Bagchi et al., 1996b), and stimulation of oncogene expression and inhibition of tumor suppressor genes (Hoffer et al., 1996, Miller et al., 1986). Thus, a common, complex pathway may exist regarding the toxicities of diverse environmental pollutants.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and endrin are environmental as well as industrial pollutants, and extensive research has provided evidence that ROS and oxidative stress are involved in the toxicity of these xenobiotics (Stohs, 1990). Investigations have shown that a 0.50 LD50 dose of sodium dichromate (chromium VI) more effectively induces formation of ROS and causes oxidative tissue and DNA damage as compared to chromium chloride (chromium III) (Bagchi et al., 1995b). The effect of an oral, low (0.05 LD50) dose of chromium VI (2.5 mg/kg/day) on hepatic and brain mitochondrial and microsomal lipid peroxidation, excretion of urinary lipid metabolites including malondialdehyde, formaldehyde, acetaldehyde and acetone, and hepatic and brain nuclear DNA-single strand breaks in Sprague–Dawley rats has shown that maximum increases in these parameters occur between 60 and 75 days of treatment. The results of these experiments clearly indicate that low dose sub-chronic administration of sodium dichromate induces an oxidative stress resulting in tissue damaging effects that may contribute to the toxicity and carcinogenicity of chromium VI (Bagchi et al., 1995c).
The toxic manifestations induced by naphthalene appear to involve the conversion of naphthalene to naphthoquinones as 1,2- and 1,4-naphthoquinone, as well as hydroxylated products including 1-naphthol, 2-naphthol and 1,2-dihydroxynaphthalene (Cho et al., 1994, Miller et al., 1986). Exposure to naphthalene is associated with the development of hemolytic anemia in humans and laboratory animals. Yamanouchi et al. (1986) demonstrated that daily 1 g/kg doses of naphthalene to rats resulted in elevated levels of serum and liver lipid peroxides, suggesting enhanced lipid peroxidation.
Germansky and Jamall (1998) observed that the oral administration of naphthalene enhanced hepatic lipid peroxidation and decreased selenium dependent glutathione peroxidase activity. Naphthalene has been shown to induce oxidative stress as evidenced by hepatic and brain lipid peroxidation, glutathione depletion, DNA-single strand breaks and membrane microviscosity, and excretion of urinary lipid metabolites in female Sprague–Dawley rats (Vuchetich et al., 1996) as well as in cultured macrophage J774A.1 cells (Bagchi et al., 1998). Furthermore, vitamin E succinate protected against these biomarkers of oxidative injury. Thus, the toxicity of naphthalene is at least in part related to free radicals and free radical-mediated oxidative stress.
In the present study, we have assessed the comparative effects of 0.01, 0.10 and 0.50 LD50 doses and 0–96 h of exposure to TCDD, endrin, naphthalene and chromium (VI) on lipid peroxidation, DNA fragmentation and enhanced production of superoxide anion (cytochrome c reduction) in liver and brain tissues of C57BL/6NTac mice in order to determine the comparative dose- and time-dependent effects produced by these structurally diverse xenobiotics.
Section snippets
Animals and treatment
Female C57BL/6NTac mice (4 weeks old) were obtained from Taconic (Germantown, NY). The animals were housed in a controlled environment at 25 °C with a 12 h light–dark cycle, and were acclimated for at least 3–5 days before use. Unless otherwise stated, all animals were allowed free access to food (Purina Rodent Lab Chow No. 5001) and tap water. The protocol for this project was approved by the Creighton University Animal Research Committee. The mice were treated with single oral (gavage) 0,
Lipid peroxidation
Dose- and time-dependent effects of the structurally diverse xenobiotics TCDD, endrin, naphthalene and chromium (VI) on brain and hepatic lipid peroxidation in C57BL/6NTac mice are given in Table 1, Table 2, respectively. Dose- and time-dependent effects were observed in all cases. No significant changes in brain or liver lipid peroxidation were observed at any timepoint following treatment with the four xenobiotics at the 0.01 LD50 dose. TCDD exhibited an increasing effect in lipid
Discussion
We have proposed that the toxicity of structurally diverse environmental toxicants may involve a common cascade of events which includes the production of ROS and an oxidative stress. Although the mechanisms for initiating ROS may vary, common events may occur as a result thereof.
In order to assess this hypothesis, the dose- and time-dependent effects of four structurally diverse xenobiotics, namely, TCDD, endrin, naphthalene, and chromium (VI) on the induction of oxidative stress and oxidative
Acknowledgments
Supported in part by grants (#94-0058 and #97-1-0016) from the Air Force Office of Scientific Research. The authors thank Dr Walter Kozumbo for scientific discussions and Ms Pansy Lim for technical assistance.
References (28)
- et al.
In vitro and in vivo generation of reactive oxygen species, DNA damage, and lactate dehydrogenase leakage by selected pesticides
Toxicology
(1995) - et al.
Chromium-induced excretion of urinary lipid metabolites, DNA damage, nitric oxide production, and generation of reactive oxygen species in Sprague–Dawley rats
Comp. Biochem. Physiol.
(1995) - et al.
Oxidative stress induced by chronic administration of sodium dichromate [Cr(VI)] to rats
Comp. Biochem. Physiol.
(1995) - et al.
Induction of oxidative stress by chronic administration of sodium dichromate [chromium VI] and cadmium chloride [cadmium II] to rats
Free Rad. Biol. Med.
(1997) - et al.
Naphthalene-induced oxidative stress and DNA damage in cultured macrophage J774A.1 cells
Free Rad. Biol. Med.
(1998) - et al.
Production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes from endrin-treated rats
Free Rad. Biol. Med.
(1993) - et al.
Comparative effects of endrin on the hepatic lipid peroxidation, DNA damage and nitric oxide production by peritoneal lavage cells from C57BL/6J and DBA/2 mice
Comp. Biochem. Physiol.
(1993) - et al.
Microsomal lipid peroxidation
Meth. Enzymol.
(1978) - et al.
Reactive naphthalene metabolite binding to hemoglobin and albumin
Fund. Appl. Toxicol.
(1994) - et al.
Comparative studies on lipid peroxidation and DNA-single stand breaks induced by lindane, DDT, chlordane and endrin in rats
Comp. Biochem. Physiol.
(1993)
Dioxin induces transcription of fos and jun genes by Ah receptor-dependent and independent pathways
Toxicol. Appl. Pharmacol.
Oxidative mechanisms in the toxicity of metal ions
Free Rad. Biol. Med.
Oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
Free Rad. Biol. Med.
Naphthalene-induced oxidative stress in rats and the protective effects of vitamin E succinate
Free Rad. Biol. Med.
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