Acetaminophen-induced forestomach lesion in normal rats following intravenous exposure

Four groups of ten male and ten female rats each were treated intravenously with saline, 400 mg/kg/day of a commercially available injectable acetaminophen formulation, or 400 mg/kg/day of a new injectable acetaminophen formulation with (aged) or without (fresh) impurities daily for fourteen days. Gross observations of the mucosal surface of the stomachs from treated rats included multifocal to diffuse pale, elevated foci confined to the nonglandular region of the stomach. Treatment-related histologic observations consisted of epithelial hyperplasia and hyperkeratosis of the nonglandular mucosa of the stomach. The epithelial hyperplasia was characterized by a thickened epithelium, frequently accompanied by the development of undulations at the basement membrane zone, resulting in the formation of rete ridgelike structures protruding into the underlying tissue. The submucosa was usually expanded by edema and occasionally contained an infiltrate of neutrophils, eosinophils, and macrophages. The hyperplasia was usually accompanied by hyperkeratosis resulting in thickening of the stratum corneum. The incidence and severity of the gastric changes were similar across all treatment regimens. Although considered clinically irrelevant since humans do not have a forestomach equivalent, these results are significant in that this appears to be the first report of forestomach hyperplasia and hyperkeratosis following intravenous exposure to acetaminophen.