X-Message-Number: 12112 Date: Sun, 11 Jul 1999 08:46:58 -0700 (PDT) From: Doug Skrecky <> Subject: reducing glycerol toxicity Citations: 1-2 <1> Authors Zurovsky Y. Eligal Z. Grossman S. Bergman M. Gafter U. Institution Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. Title Glycerol-induced augmentation of sensitivity to endotoxin in rats. Source Toxicon. 32(1):17-26, 1994 Jan. Abstract Combined sepsis and rhabdomyolysis result in a mortality rate much higher than that caused by each process alone. An analogous rat model is obtained by simultaneous i.p. administration of a nonlethal dose of lipopolysaccharide (LPS 0.025 mg/100 g) and a nonlethal i.m. injection of glycerol (1 ml/100 g). The aim of this study was to determine the factors contributing to the high mortality rate in this rat model. The factors examined include: Dehydration, plasma volume expansion, 'immunization' to glycerol, induction of LPS tolerance and the effect of free radicals formed in this model. Neither dehydration nor volume expansion affected mortality. 'Immunization' with glycerol was also not effective. In contradistinction, tolerance to LPS achieved by a daily injection with gradual increasing doses of LPS (from 0.05 mg/100 g to 1 mg/100 g) for 6 days reduced the mortality rate by 60% (P < 0.001). Moreover, decreasing free radical activity using the natural antioxidant (NAO) (5 mg/100 g) reduced mortality rates by 50%. A different antioxidant, dimethylthiourea (DMTU) (50 mg/100 g) failed to reduce mortality rates. This study suggests that the synergism between glycerol and LPS is apparently due to an increase in the rats' sensitivity to endotoxin following glycerol injection. However, endotoxin apparently does not enhance sensitivity to glycerol in the rat. The new antioxidant NAO significantly reduced the high mortality rate. <2> Authors Uche EM. Arowolo RO. Akinyemi JO. Title Toxic effects of glycerol in Swiss albino rats. Source Research Communications in Chemical Pathology & Pharmacology. 56(1):125-8, 1987 Apr. Abstract The acute toxicity of glycerol was studied in swiss albino rats. The median lethal dose (LD50) of glycerol in the local strain of swiss albino was determined to be 4.42 gm/kg body weight. Nervous signs were observed in the rats before death. Organ: body weight ratios of the heart, kidneys and liver were higher than normal, while those of the spleen and brain remained normal. No gross pathological lesion of these organs was observed. The histopathological lesions observed include congestion of blood vessels of the lungs and kidneys; accumulation of hemoglobin in renal tubules; renal tubular epithelial degeneration and desquamation; neuronal degeneration and necrosis, as well as occurrence of haemosiderin pigments. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=12112