D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

Abstract

Background: Short-term administration of Galactosamine to experimental animals causes liver damage and acute liver failure (ALF), as well as acute renal failure in some cases. The aim of our study was to describe kidney disorders that developed in the course of galactosamine-induced liver failure.

Material and methods: Sprague-Dawley rats were randomly divided into 2 groups: a study group administered galactosamine intraperitoneally and a control group administered saline.

Results: All the animals in the study group developed liver damage and failure within 48 h, with significant increase of alanine (p<0.001), aspartate aminotransferases (p<0.0001), bilirubin (p<0.004), and ammonia (p<0.005) and decrease of albumin (p<0.001) concentrations. Acute renal failure was observed in all test animals, with a significant increase in creatinine (p<0.001) and urea (p<0.001) concentrations and a decrease in creatinine clearance (p<0.0012). Moreover, osmotic clearance (p<0.001), daily natriuresis (p<0.003), and fractional sodium excretion (p<0.016) decreased significantly in this group of animals. The ratio of urine osmolality to serum osmolality did not change. Histopathology of the liver revealed massive necrosis of hepatocytes, whereas renal histopathology showed no changes.

Conclusions: Acute renal failure that developed in the course of galactosamine-induced ALF was of a functional nature, with the kidneys retaining the ability to concentrate urine and retain sodium, and there were no renal changes in the histopathological examination. It seems that the experimental model of ALF induced by galactosamine can be viewed as a model of hepatorenal syndrome that occurs in the course of acute damage and liver failure.

Figure 1

Profile of liver parameters after galactosamine intoxication. Within 48 h, administration of galactosamine caused severe liver damage and the development of acute liver failure with an increase of the serum levels of ALT, bilirubin, and ammonia. ALT – alanine aminotransferase. * p<0.05, values are means ±SD.

Figure 2

(A) Histopathological examination of the liver in sham rats. Lack of necrosis of hepatocytes in the liver from sham rats (Group 1) at 48 h after saline injection. Hematoxylin and eosin staining, light microscope, magnification ×20. (B) Histopathological examination of the liver in test rats. Diffuse necrosis of hepatocytes in the liver from test rats (Group 2) at 48 h after galactosamine injection. Diffused degenerative changes, including small and giant cells, infiltrations of eosinophilic granulocytes, portal tract fibrosis, and hyperemia. Hematoxylin and eosin staining, light microscope, magnification ×20.

Figure 3

Profile of renal parameters after galactosamine intoxication. Galactosamine administration resulted within 48 h in the development of acute functional renal failure with a reduction in creatinine clearance, fractional sodium excretion and osmotic clearance. * p<0.05, values are means ±SD.

Figure 4

(A) Histopathological examination of the kidney in sham rats. Lack of morphological changes in the kidney from sham SDR rats (Group 1) at 48 h after saline injection. Hematoxylin and eosin staining, light microscope, magnification ×20. (B) Histopathological examination of the kidney in test rats. Lack of morphological changes in the kidney from test rats (Group 2) at 48 h after galactosamine injection. Hematoxylin and eosin staining, light microscope, magnification ×20.