GLUTATHIONE AND PHOSPHOLIPID DEPLETION OF LIVER-TUMORS AFTER ARTERIALISCHEMIA

Breakdown of membrane phospholipids is a causative event leading to ir reversible cell injury after ischemia and reperfusion insults, which m ight be one mechanism leading to liver tumor cell death after repeated arterial ischemia as well. After 2 hr of hepatic dearterialization fo llowed by 30 min of reperfusion tumor phospholipid was measured chroma tographically, glutathione (GSH) analyzed by determining nonprotein su lfhydryl and activity of glutathione-S-transferase (GST) determined sp ectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as the s ubtrate. A transient, arterial ischemia for 2 hr induced a substantial decrease of phosphatidylserine (PS) and phosphatidylinosital (PI) com pared with sham treatment (P < 0.01). Although phosphatidylcholine (PC ) and phosphatidylethanolamine (PE) did not significantly decline afte r a single arterial ischemia for 2 hr, they dropped dramatically follo wing repeated arterial ischemia for 2 hr during 5 days (P < 0.01 and P < 0.05 respectively). GSH was depleted in tumors after both a single (P < 0.01) and repeated arterial ischemia (P < 0.05) and GST was inact ivated as well (P < 0.001). By contrast, neither liver phospholipid no r liver GSH or GST was significantly changed. Tumor growth was signifi cantly retarded in rats subjected to repeated arterial ischemia compar ed with sham treatment (P < 0.01). Repeated arterial ischemia facilita ted degradation of tumor membrane phospholipids and induced depletion of GSH and inactivation of GST without affecting the normal liver. Thu s, ischemia/reperfusion induced depletion of membrane phospholipids an d of GSH might represent two mechanisms by which repeated arterial isc hemia led to tumor growth delay. (C) 1996 Wiley-Liss, Inc.