Abstract
DHG, a glycosaminoglycan extracted from the sea cucumber is known to show antithrombotic effects in animals and be a possible therapeutic agent for prevention of disseminated intravascular coagulation. In toxicology study, however, dose-dependent intracellular deposition of eosinophilic or basophilic droplets, and crystalloid substances were observed in the proximal tubular epithelial cells of the kidneys when male Sprague-Dawley rats were administered DHG daily for two weeks at the doses of 10, 100, and 200 mg/kg. In contrast to heparin, a glycosaminoglycan that has been reported to induced similar deposits which were identified to be composed of a hemoglobin-like substance using the alizarin red staining. The inclusions observed in rats given DHG were immunohistochemically positive for α2u-globulin. Moreover, the droplets showed metachromasia in toluidine blue staining, and negative for Hall's, Gmelin's, Schmol's tests, and alizarin red staining, but the crystalloids were positive for alizarin red staining. These results suggested that DHG-induced degeneration of proximal tubular epithelial cells in male rats is related to α2u-globulin accumulation.