Protective effects of alpha-lipoic acid against benzene induced toxicity in experimental rats.

OBJECTIVE: The aim of the present study was to examine the potential protective effects of Alpha-Lipoic Acid (ALA) against benzene induced alteration in CYP2E1 gene function, DNA damage as well as the oxidant-antioxidant status. MATERIALS AND METHODS: Fifty adult male Wister rats were used for this study. Rats were randomized and divided into four groups: Group I was designated as control group and received a vehicle of olive oil; Group II was received alpha lipoic acid in a dose of (20 mg/kg, i.p.); Group III received only I.M. injection of benzene in a dose of 2 ml/kg. Group IV received both alpha lipoic acid in a dose of (20 mg/kg, i.p.) and I.M. injection of benzene in a dose of 2 ml/kg. The animals were treated on each alternate day for 30 days then all rats were sacrificed and both blood and liver tissue samples were taken to measure serum malondialdehyde (MDA) Level; serum level of reduced glutathione (GSH); level of serum 8-hydroxy-2'-deoxyguanosine; hepatic microsomal cytochrome P450 2E1 activity and gene expression. RESULTS: Benzene significantly increased serum malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and both CYP2E1 activity and gene expression but significantly decreased level of reduced glutathione (GSH). These changes are reversed upon administration of ALA. CONCLUSIONS: The current study provided evidence that the linkage between CYP2E1-dependent oxidative stress, DNA damage, and GSH homeostasis could contribute to the toxic actions of benzene which can be counteracted by ALA by its suppression action on CYP2E1, inhibition of lipid peroxidation and oxidative DNA damage as well as maintenance of intracellular antioxidants status.

Interactions between Trichinella spiralis infection and induced colitis in mice.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation afflicting any part of the bowel wall as a result of a deregulated and inappropriate immune response. In recent years, experimental and clinical evidence has demonstrated that infection with parasitic worms could protect hosts from IBD. The aims of this study were to determine if the underlying mechanism of the host immune regulation inherent to Trichinella spiralis infection involves Foxp3-expressing regulatory T cells, and to gain insight about time-related interactions between intestinal nematode infection and induced colitis using an experimental model for ulcerative colitis. Mice were experimentally subjected to acetic acid-induced colitis, which was either preceded or followed by T. spiralis infection. Assessment of colitis was done by histopathological examination of the colon and determination of pentraxin 3 levels. Immunohistochemistry was done for demonstration of Foxp3-expressing regulatory T cells in colonic tissues. It was evident that T. spiralis infection ameliorated the severe inflammation induced by acetic acid, evidenced by amelioration of histopathological changes and diminution of pentraxin 3 levels. The amelioration was more pronounced when T. spiralis infection preceded the induction of colitis. Regarding the immunohistochemical staining of regulatory T cells, T. spiralis infection induced recruitment of Foxp3-expressing regulatory T cells to areas of inflammation. In conclusion, T. spiralis regulatory mechanism can improve inflammation of the colon through the 'inflammatory-regulatory' axis. Finally, it would be of great importance to apply these results to the development of new therapeutic approaches for the treatment of ulcerative colitis.