Glutathione and phospholipid depletion of liver tumors after arterial ischemia.
Breakdown of membrane phospholipids is a causative event leading to irreversible cell injury after ischemia and reperfusion insults, which might be one mechanism leading to liver tumor cell death after repeated arterial ischemia as well. After 2 hr of hepatic dearterialization followed by 30 min of reperfusion tumor phospholipid was measured chromatographically, glutathione (GSH) analyzed by determining nonprotein sulfhydryl and activity of glutathione-S-transferase (GST) determined spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as the substrate. A transient, arterial ischemia for 2 hr induced a substantial decrease of phosphatidylserine (PS) and phosphatidylinosital (PI) compared with sham treatment (P < 0.01). Although phosphatidylcholine (PC) and phosphatidylethanolamine (PE) did not significantly decline after a single arterial ischemia for 2 hr, they dropped dramatically following 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 inactivated as well (P < 0.001). By contrast, neither liver phospholipid nor liver GSH or GST was significantly changed. Tumor growth was significantly retarded in rats subjected to repeated arterial ischemia compared with sham treatment (P < 0.01). Repeated arterial ischemia facilitated degradation of tumor membrane phospholipids and induced depletion of GSH and inactivation of GST without affecting the normal liver. Thus, ischemia/reperfusion induced depletion of membrane phospholipids and of GSH might represent two mechanisms by which repeated arterial ischemia led to tumor growth delay.
Wang
L Q
LQ
Department of Surgery, Lund University, Sweden.
Persson
B G
BG
Xu
N
N
Seidegård
J
J
Jeppsson
B
B
Bengmark
S
S
D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006499:Hepatic Artery; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF
D010743:Phospholipids; D005982:Glutathione Transferase; D005978:Glutathione