Hepatoprotective effects of vitamin E against hexachlorobenzene-induced hepatotoxicity and oxidative stress in rats: histological, biochimical and antioxidant status changes.

The protective effects of α-Tocopherol (vitamin E) on liver injury induced by hexachlorobenzene (HCB) were investigated in adult male rats of Wistar strain. Animals were randomly divided into six groups of eight rats each. Group 1 and 2 have received HCB, dissolved in olive oil, at a dose of 4 mg or 16 mg/kg b.w., respectively. Group 3 and 4 were treated by the same doses of HCB (4 mg and 16 mg/kg b.w.) after 1 h of pretreatment with α-tocopherol at a dose of 100 mg kg-1 b.w. The other two groups served as controls; which received either olive oil only, a solvent of HCB, or α-tocopherol. A significant increase in hepatic lipid peroxidation (LPO) and GSH activity were observed following HCB administration. The activities of antioxidant enzymes like superoxide dismutase and catalase were significantly decreased while glutathione peroxidase was significantly increased following HCB administration. Similarly, a significant increase in plasma levels of various marker enzymes [aminotransferase (aspartate aminotransférase (AST) and alanine aminotransferase (ALT)), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and a decrease of total protein level were observed. Pretreatment with vitamin E of HCB treated rats ameliorated all biochemical parameters to near normal values. Liver histological study confirmed biochemical parameters and the beneficial role of vitamin E.

Irreversible thyroid disruption induced after subchronic exposure to hexachlorobenzene in male rats.

Thyroid hormones play a complex role in the toxicity of hexachlorobenzene (HCB) and related compounds. Time-course and dose-response experiments for free- and total thyroxine (T4) and triiodothyronine (T3) plasma levels for thyroid-stimulating hormone (TSH) and thyroid gland histomorphology were determined in male Wistar rats. Also, we examined the possible reversibility of changes noted after removal of HCB. Rats treated with this organochlorine compound resulted in a hypertrophy of the thyroid gland and altered thyroid function by decreasing significantly the levels of total- and free T4 in a dose-dependent manner (total T4: 28 and 51%; free T4: 21 and 37%), and this decrease was seen as early as 21 days and thereafter. Free T3 was also decreased by 21% with the highest dose starting from day 21. No significant changes were observed in the circulating levels of total T3 In response to the decrease of thyroid hormones, a dose-dependent increase of TSH levels (27 and 31%, respectively, for 4 mg and 16 mg/kg of HCB body weight) was observed after 21 days of HCB treatment. We have observed a hypertrophy and hyperplasia of follicular cells and a decrease in colloid volume in histological picture. When HCB was removed and changed by vehicle, the thyroid relative weight and plasma TSH continued to rise and serum thyroid hormones remained suppressed. These findings suggest that subchronic exposure of rats to HCB induced an irreversible hypothyroidism state.

DNA damage and oxidative stress induced at low doses by the fungicide hexachlorobenzene in human intestinal Caco-2 cells.

CONTEXT: Hexachlorobenzene (HCB), a persistent chlorinated organic chemical, could be detected in human tissues in several countries of the world. Human exposure to Persistent Organic Pollutants (POPs) occurring primarily through diet, HCB and its metabolites are therefore supposed to interact directly with intestinal mucosa. OBJECTIVE: The aim of this study was to investigate the possible effects of low doses of HCB on DNA integrity, cellular viability, differentiation and oxidative status in vitro in human colonic carcinoma cell line Caco-2. MATERIALS AND METHODS: Cells were exposed to increasing doses of HCB for 14 days to assess the cytotoxic, genotoxic and oxidative properties of this compound. The involvement of oxidative stress in the observed effects was evaluated by co exposure of Caco-2 cells with HCB and α-tocopherol. RESULTS: Exposure of Caco-2 cells to HCB resulted in a dose-dependent cytotoxicity, DNA damages and alterations of the cell layer integrity and the barrier function. Moreover, exposure of Caco-2 cells to HCB led to an enhancement of H(2)O(2) production and to an increased activity of antioxidant enzymes. In addition, Co exposure of Caco-2 cells to HCB and α-tocopherol reversed the effects observed in cells exposed to HCB alone. CONCLUSION: These results suggested that HCB effects on Caco-2 cells could be linked, at least in part, to its pro-oxidative potential.