Pre-clinical Safety Evaluation of Soluble Glucan

Int J Immunopharmacol. 1988;10(4):405-14. doi: 10.1016/0192-0561(88)90127-0.

Abstract

Soluble glucan, a beta-1,3-linked glucopyranose biological response modifier, is effective in the therapy of experimental neoplasia, infectious diseases and immune suppression. Currently, soluble glucan is undergoing phase I clinical trials. The present study describes the pre-clinical safety evaluation of soluble glucan in mice, rats, guinea pigs and rabbits. ICR/HSD mice and Harlan Sprague-Dawley rats received a single i.v. injection of soluble glucan in doses ranging from 40 to 1000 mg/kg. Soluble glucan administration did not induce mortality, appearance or behavioral changes in mice or rats. In subsequent studies, mice and guinea pigs were injected i.p. with glucan (250 mg/kg) for 7 consecutive days. ICR/HSD mice gained weight at the same rate as the saline-treated controls. In contrast, guinea pigs receiving i.p. injections of soluble glucan showed a significant (P less than 0.05) 10-13% decrease in weight gain over the 7 day period. No other toxicologic, behavioral or appearance changes were noted. To examine chronic toxicity, soluble glucan was administered twice weekly for a period of 30 or 60 days to ICR/HSD mice in the dose of 40, 200 or 1000 mg/kg. No deaths were observed in any group. Chronic glucan administration did not alter body weight, liver, lung or kidney weight. However, a significant splenomegaly was observed in both the 30 and 60 day study. Histopathologic examination showed no tissue alterations at 40 or 200 mg/kg. However, at 1000 mg/kg a mononuclear infiltrate was observed in the liver. Pyrogenicity testing, employing New Zealand white rabbits, revealed that parenteral glucan administration (5 mg/kg) did not significantly alter body temperature. These data indicate that the systemic administration of soluble glucan, over a wide dose range, does not induce mortality or significant toxicity, an important consideration in preparing soluble glucan for parenteral administration to human populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Drug Evaluation, Preclinical
  • Female
  • Fever / chemically induced
  • Glucans / toxicity*
  • Guinea Pigs
  • Interleukin-1 / biosynthesis
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Organ Size / drug effects
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Solubility
  • Species Specificity

Substances

  • Glucans
  • Interleukin-1