X-Message-Number: 12112
Date: Sun, 11 Jul 1999 08:46:58 -0700 (PDT)
From: Doug Skrecky <>
Subject: reducing glycerol toxicity

Citations: 1-2
  Zurovsky Y.  Eligal Z.  Grossman S.  Bergman M.  Gafter U.
  Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
  Glycerol-induced augmentation of sensitivity to endotoxin in
  Toxicon.  32(1):17-26, 1994 Jan.
  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.

  Uche EM.  Arowolo RO.  Akinyemi JO.
  Toxic effects of glycerol in Swiss albino rats.
  Research Communications in Chemical Pathology & Pharmacology.  56(1):125-8,
  1987 Apr.
  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.

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