Impact of 30-Day Oral Dosing With N-Acetyl-L-Cysteine on Sprague-Dawley Rat Physiology
Final rept. Mar-Dec 2003
NAVAL HEALTH RESEARCH CENTER (DET) WRIGHT-PATTERSON AFB OH ENVIRONMENTAL HEALTH EFFECTS LAB
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A number of studies have demonstrated a protective effect associated with N-acetyl-L-cysteine NAC against toxic chemical exposure. However, the impact of long-term oral dosing on tssue pathology has not been determined. In this study, we assessed the impact of long-term oral NAC administration on organ histopathology and tissue glutathione GSH and total glutathione-S-transferase GST activity levels in Sprague-Dawley SD rats. Groups of 20 SD rats 10 male, 10 female, 8 weeks of age, were dosed daily by oral gavage with deionized H2O negative controls or NAC solution at a rate of 600 or 1,200 mglkgld for 30 days. Animals were euthanized 6 hours after treatment on study Day 30. There were no significant differences in final body weights or weekly average weight gain between treatment groups. Serum alanine aminotransferase ALT activities were significantly elevated p less than or equal to 0.05 in NAC-treated animals compared to controls when measured on study Day 30. Histopathologic evaluation of the liver, stomach, small intestine, liver, kidneys, spleen, thymus, and lungs revealed no lesions associated with NAC administration. When measured on study Day 30, total GST acUvity for kidney and skin from NAC-treated animals were increased 39-131 as compared to controls. Tissue GSH concentrations from NAC-treated animals were increased 24-81 as compared with negative controls. Further studies are needed to determine if the observed increase in tissue GSH concentraion and GST activity provide a degree of chemoprotection against dermal and systemic chemical toxicants.
- Anatomy and Physiology