Exp Toxic Patho11997; 49: 141-146 Gustav Fischer Verlag Institute of Biochemistry, Academy of Sciences of Belarus, Grodno, Belarus 'Institute of Pathobiochemistry, Friedrich Schiller University, Jena, Germany Antioxidative effect of prostaglandin E2 in thioacetamide-induced liver cirrhosis VYACHESLAV BUKo, OXANA LUKIVSKAYA, VASIUY NIKITIN, ALEXANDR KURYAN and ROLF DARGEL 1 With 2 figures and 2 tables Received: January 23,1996; Accepted: February 15, 1996 Address for correspondence: Prof. Dr. Vy ACHESLA v BUKo, Institute of Biochemistry, Academy of Sciences of Belarus, Tarashkevich Boulevard 50, 230017 Grodno, Belarus. Key words: Prostaglandin E 2 ; Liver cirrhosis; Thioacetamide-induced liver cirrhosis; Antioxidative effect, prostaglan- din Er Abbreviations: PGE 2 -Prostaglandin E 2 , MDA-malondialdehyde, T AA-thioacetamide Summary Several studies provided evidence that various prostag- landins exhibited a hepatoprotective effect in vivo as well in vitro the mechanism of which is still in debate. Therefore, the aim of our studies was to examine the effect of PGE 2 on some biochemical and morphological alterations in chemi- cally induced liver cirrhosis in rats. A micronodular liver cirrhosis was induced by treatment of rats with thioaceta- mide for 3 months. Morphologically, the administration of PGEJ for 8 days reduced the extent of vacuolar transforma- tion of the hepatocytes and the density of the nuclear struc- ture without affecting the fibrotic state as assessed by the hepatic hydroxyproline content. The widening of the sinu- soids indicated an improved hepatic microcirculation. Ad- ministration of PGE 2 significantly elevated the percentage portion of arachidonic (20:4) and docosapentaenoic (22:5) acid in the hepatic phospholipids and reduced the ratio 20:3120:4 fatty acids in comparison to the untreated cirrho- tic animals. The hepatic MDA concentration was decreased by 40 % in PGE 2 -treated animals. PGE 2 treatment also re- duced the content of polar as well as of non-polar carbonyls when compared with the controls. Moreover, treatment with PGE 2 lowered iron-induced or iron plus ascorbate-in- duced MDA production of isolated hepatocytes. From the data it was concluded that the hepatoprotective effect of PGE 2 may be related to its antioxidative capacity. Introduction Some prostaglandins are known as hepatoprotective agents in fatty liver (BuKO 1991), hepatitis (NILIUS 1990) and liver cirrhosis (BRENNER and ALCORN 1990). The be- neficial effect of PGE is explained by its antifibrogenic reaction, its positive effect on hemodynamics, and by in- hibition of prolyI4-hydroxylase. The synthetic derivative of PGE, l6,16-dimethyl-PGE 2 , inhibits collagen biosyn- thesis in rats receiving a cirrhogenic diet (RUWART et al. 1990). PGE as vasodilatators are known to support renal function in cirrhotic patients with the hepatorenal syn- drome (DAVIDSON and DUNN 1987) and in experimental liver cirrhosis (LEEHA Yet al. 1989). Recently, we demonstrated that PGE z acted as an anti- oxidant in alcoholic liver steatosis decreasing free radical generation by the microsomal cytochrome P-450 system and lowering MDA and other carbonyl-containing pro- ducts of lipid peroxidation in the liver (BuKO and SA- DOVNICHY 1996). As was demonstrated previously, lipid peroxidation was altered in T AA -induced cirrhotic rat liver (MOLLER et al. 1991). Therefore, the aim of this work was to study the effect of PGE 2 on lipid peroxida- tion and some biochemical and morphological alterations in the rat liver caused by the pretreatment with TAA. Material and methods Chemicals: All chemicals were of reagent grade and were obtained from the following sources: collagenase, bo- vine serum albumin, and HEPES from Serva (Germany); si- lica gel G, malondialdehyde bisdimethylacetat, and dinitro- phenyl hydrazine from Sigma (USA); FeS0 4 x 7Hp from Merck (Germany); thioacetamide from P.O.C.H. (Poland); PGE 2 from Kemasol (Estonia); L-ascorbic acid and other chemicals from Laborchemie Apolda (Germany) and Rea- chim (Russia). Exp Toxic Pathol49 (1997) 1-2 141