Chronic toxicity of taurohyodeoxycholic acid in rats.

Fifty-two-week oral toxicity and 24-week intraperitoneal toxicity of a new synthetized biliary acid, taurohyodeoxycholic acid (Io, Praxis, CAS 2958-04-5), were investigated in rats. Taurohyodeoxycholic acid was orally administered at dose levels up to 500 mg/kg/d and intraperitoneally administered at dose levels up to 200 mg/kg/d. The treated animals showed no deviations from normality in mortality, physical appearance and general behavior. Food and water consumption and body weight gain of the treated groups did not differ from those of the control. No treatment-related changes were observed in hematology, serum biochemistry, urinalysis, organ weights and post-mortem macroscopic or histopathological examinations. No dose- or sex-related differences were observed. The no-effect dose level was estimated to be 500 mg/kg/d in the chronic oral toxicity study and 200 mg/kg/d in the intraperitoneal study.

Chronic toxicity study on a new glucan extracted from Candida albicans in rats.

Fifty-two-week oral toxicity of a new glucan (Glucanil, Gluimmun) extracted from Candida albicans ATCC 20955 was investigated in rats. The glucan was orally administered in dose levels up to 200 mg/kg/d and was well tolerated. No deviation from normality was observed in mortality, physical appearance and general behaviour of the treated animals. Food and water consumption and body weight gain of glucan-fed groups did not differ from those of control animals. In these groups no alteration of the weight of the main organs was also observed. Hematology, blood chemistry, urinalysis and autopsy findings were within normal ranges in every group of rats treated. No sex difference was noted. In the 200 mg/kg group soft stools or diarrhoea and cecal enlargement with variable hyperplasia of the colon mucosa were observed. These symptoms are typical of exposure to substances which are absorbed incompletely in the small intestine and subjected to microbial metabolism in the cecum and colon. Diarrhoea, cecal enlargement and mucosal hyperplasia are reversible. The no-effect dose level was estimated to be 100 mg/kg/d under these conditions.

Preliminary evaluation of immunoadjuvant activity of an orally administered glucan extracted from Candida albicans.

The immunoadjuvant activity of an orally administered glucan (Glucanil, Gluimmun) was investigated in mice. Glucan was extracted from Candida albicans ATCC 20955 and purified by an alkali-acid and detergent treatment. In this study the chronic intravenous infection with Candida albicans (treated or not with amphotericin B) or Staphylococcus aureus was the experimental model. Moreover the production of interleukin-2 was evaluated in treated animals. Oral treatment with glucan at 1 mg/mouse/day repeated doses, starting from 10 days before the experimental infection, significantly increased polymorphonuclear leukocytes and peripheral monocytes number. A significant increase in number and in vitro candidacidal activity was also observed for alveolar macrophages. The resistance towards systemic infection with Candida albicans or Staphylococcus aureus increased, significantly reducing the growth of microorganisms in the kidneys of infected animals. Glucan significantly increased the candidacidal spleen cells activity and synergized with amphotericin B chemotherapeutic action. Higher doses (eg. 2 or 5 mg/mouse) were not effective. A 10 days oral treatment with 1 mg/mouse/d significantly increased the interleukin-2 production. Toxicological studies showed that glucan is highly tolerated.