Cytoprotective effect of 16, 16' dimethyl prostaglandin E2 and some drugs on an acute galactosamine induced liver damage in rat

Present experiment was aimed to study whether 16, 16' dimethylprostaglandin E2 (dmPGE2), Hepatofalk (HF), or Orotofalk (OF) may prevent an acute liver damage induced in rats with D-galactosamine (GalN). Fifty male rats were divided into 5 groups: 1. controls, 2. rats receiving GalN 750 mg/kg b. w. intraperitoneally, 3. animals pretreated with 5 microgram/kg dmPGE2 given subcutaneously 24 hours prior to, 30 min prior to and 6 hours after GalN. Rats of group 4 received HF 0,8 ml/kg intramuscularly and group 5 OF 0,3 caps/kg intragastrically 24 hours prior to, 30 min prior to and 6 hours after GalN. Animals were sacrificed 24 hours after GalN injection. Histological, histochemical and ultrastructural studies of the liver were performed. In rats receiving GalN alone (group 2) typical severe liver damage consisting of acidophilic necrosis of hepatocytes, periportal and intralobular inflammatory infiltration, hypertrophy and hyperplasia of Browicz-Kupffer cells has been observed. Histochemical investigations showed in this group fatty degeneration and a decrease in glycogen content in hepatocytes, irregular distribution of lysosomes, numerous cytolysosomes and uneven decrease in lysosomal enzymes activity (acid phosphatase and beta-glucuronidase). Ultrastructural studies revealed depletion in glycogen, fat droplets, hypertrophy of smooth endoplasmic reticulum and numerous autophagic vacuoles. Some of these vacuoles or residual bodies were dropping out into intercellular space. Focal accumulation of lamellar cytomembranes as well as condensation of heterochromatin in nuclei were also observed. Pretreatment of animals with dmPGE2 (group 3), HF (group 4) or OF (group 5) prior to GalN prevented liver cell necrosis. Histological, histochemical and ultrastructural picture of the liver was in these groups close to normal. Only very slight hypertrophy and hyperplasia of Browicz-Kupffer cells, was seen as well as depletion of glycogen and hypertrophy of smooth endoplasmic reticulum in hepatocytes. We conclude dmPGE2, HF and OF offered impressive cytoprotection against GalN induced liver damage in rat.