In flammopharmacology. 1991;1:49-60. Copyright t[~ Kluwer Academic Publishers by - Printed in the Netherlands SOLCOSERYL PREVENTS INFLAMMATORY AND HYPOXIC BUT NOT TOXIC LIVER DAMAGE IN RODENTS T. HARTUNG, M. LEIST, G. TIEGS, W. BASCHONG* and A. WENDEL** Faculty of Biology, University of Konstan7~ POB 5560, D-7750 Konstanz, Germany *M.E. Mfdler Institute at the Biocenter, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland **correspondence address ABSTRACT Hartung T, Leist M, Tiegs G, Baschong W, Wendel A. Solcoseryl prevents inflammatory and hypoxic but not toxic liver damage in rodents. Inflammopharmacology. 1991;1:49-60. Soictr~ryt is a non-toxic, low-molecular-weight fraction of blood from veal calves, which is in clinical use against hypoxic conditions frequently associated with chronic inflammation. The pharmaco- dynamic actions of this haemo--dialysate were studied in different types of liver damage, including hepatic lesions induced/n v/vo in mice by direct hepatotoxins or by endotoxin plus galactosamine. The isolated liver was perfused under hypoxic conditions. In addition, /n vitro experiments with Kupffer cell/hepatocyte eocultures were carried out. Solcoseryt proved to be effective in protecting against endotoxin-induced liver damage in vivo. Perfnsion with Solcoseryl reduced hylX~xic liver damage in the /n s/tu perfused mouse liver. In the /n v/tro model, the preparation prevented endotoxin-induced lesions, but not xenobiotic-induced toxic lesions. In line with these findings, Soleoseryl inhibited the endotoxin-indueible release of turnout necrosis factor~ from isolated Kupffer cells. This eytokine is known to be deleterious in several inflammatory pathomechanisms including endotoxin-induced hepatic lesions. It is concluded that Solcoseryl interacts with specific endogenous cytotoxicity mechanisms. Keywords: endotoxin, Solcoseryl, hypoxia, tumour necrosis factor-a, liver injury INTRODUCTION Solcoseryl is the low-molecular-weight fraction of a calf blood dialysate. So far, more than 80 substances have been identified in this fraction. Its influence on hepatotoxicity in vivo and in v/tro was studied in order to elucidate possible mechanisms involved in its beneficial action in ischaemia-related chronic inflammations such as ulcus cruris and decubitus. Solcoseryl has been clinically used for many years to treat dermal and mucosal injuries as well as peripheral and cerebral vascular disorders [1,2]. These indications for Solcoseryl cannot easily be ascribed to a single pathophysiological mechani.~m. It seems that Solcoseryl antagonizes various processes that interfere with the integrity of the local microcirculation [3]. ABBREVIATIONS LPS: lipopolysaccharide, endotoxin TNF: tumour necrosis factor KC: Kupffer cells PC: parenehymal ceils, hepatocytes GAIN: galactosamine LDH: lactate dehydrogenasr (EC.1.1.1.27) BST: bromo~ulphthalein, sulphobromophthalein ALT: alanine aminotransferase, glutamate/ pyruvate transaminase (GPT) (E.C.2.6.1.2) ROS: reactive oxygen species