Epidermal growth factor reduces multiorgan failure induced by thioacetamide

Abstract

Background-Multiorgan failure is a severe life threatening state where present therapeutic approaches are suboptimal. Epidermal growth factor (EGF) is a potent stimulant of repair in in vitro and in vivo models. We therefore examined its potential beneficial eVect in reducing mortality and injury induced by the noxious agent thioacetamide (TAA). Methods-Mice (20 per group) were fasted overnight and received a single intraperitoneal dose of human recombinant EGF at 10 or 30 µg/kg or saline (control). Either 30 minutes before or after EGF, all animals also received TAA (40 mg/kg intraperitoneally). Twenty four hours later, surviving animals were killed, tissues collected, and degree of organ injury assessed. Results-Fifty per cent (10/20) of control animals died within the first 24 hour period. Mortality was almost completely prevented by the higher dose of EGF whether given before or after TAA (p<0.01) and was reduced by about 50% with the lower dose of EGF. In control animals, the entire length of the jejunum and ileum had necrosis with or without mucosal denudation. In contrast, necrosis aVected only about 10-20% of the total length in EGF treated groups (both p<0.01 v control). Control animals showed marked glomerular tuft collapse, interstitial haemorrhage, and increased plasma creatinine levels. These eVects were significantly reduced in animals given EGF (30 µg/kg; p<0.01). All groups showed similar changes in liver histology (centrilobular necrosis) and alanine transaminase levels (10-fold increase). Conclusions-Although EGF did not prevent the hepatotoxicity associated with TAA, it reduced mortality, renal injury, and gastrointestinal damage. These studies provide preliminary evidence that EGF may be a novel approach for the prevention and/or treatment of multiorgan failure. (Gut 2001;48:34-40)

Liver injury after an aggressive encounter in male mice

“…This is in contrast to the heart or gastric mucosa in which EGF protects against acute stressinduced injury (11,42). However, a lack of liver protection by exogenous EGF administration was also described by Caballero et al (14) in a model of thioacetamide-induced multiorgan failure. These authors observed however, that exogenous EGF did protect the small intestine and kidneys.…”

Contribution of hepatic adenosine A1 receptors to renal dysfunction associated with acute liver injury in rats

“…Light microscopic examination of the renal tissue found only minor degenerative acute alterations in the proximal tubules but without significant signs of tubular necrosis or loss of tubule patency, results generally in agreement with previous observations. 31,32 Renal function assessment also revealed no significant changes in fractional sodium excretion or free water and osmolar clearance in rats that received TAA, indicating the renal tubules retained the ability to concentrate urine. These results suggest that the decreased urine production observed in rats that received TAA in the present study was not likely to have been caused by the direct toxic effects of TAA on renal tissue but was related mainly to the alteration in renal function from the decrease in the GFR and the increased tubular reabsorption of water and sodium.…”

A calcified caecal mass

“…There are however a number of serious gastrointestinal pathologies where novel therapies might prove useful, including their use for multiorgan failure, 4 necrotising enterocolitis, 5 and liver protection and regeneration. 6 Three conditions worthy of particular focus are short bowel syndrome, chemotherapy induced mucositis, and inflammatory bowel disease. These are discussed further below.…”