PMID- 9930921 OWN - NLM STAT- MEDLINE DCOM- 19990819 LR - 20191102 IS - 0946-2716 (Print) IS - 0946-2716 (Linking) VI - 77 IP - 1 DP - 1999 Jan TI - Monoclonal antibody to tumor necrosis factor-alpha modulates hepatocellular Ca2+ homeostasis during hemorrhagic shock in the rat. PG - 8-13 AB - Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of shock-induced cellular and humoral inflammatory cascades. The present study investigated the role of TNF-alpha in oxidative membrane injury and altered hepatocyte Ca2+ regulation, both of which are critical steps in cellular dysfunction during ischemia/reperfusion events. Hemorrhagic shock was induced by bleeding male Sprague-Dawley rats (200-250 g, n=6/group) to a mean arterial blood pressure of 40 mmHg for 60 min. Rats were resuscitated with 60% of shed blood and twice the shed blood volume as Ringers' lactate. At the end of hemorrhage and 60 min after resuscitation, hepatocytes were isolated by liver collagenase perfusion. Hepatocyte Ca2+ uptake (Ca2+up) and Ca2+ membrane flux (Ca2+flux) were determined by 45Ca2+ incubation techniques. Hepatocyte reduced/oxidized glutathione and lipid peroxidation were determined fluorometrically. Both hemorrhage and hemorrhage/resuscitation significantly increased hepatocyte Ca2+up and Ca2+flux. The monoclonal chimeric mouse gamma1 TNF-alpha antibody (TN3gamma1.19.12; 20 mg/kg b.w.) given with resuscitation significantly decreased hepatocyte Ca2+up and Ca2+flux and prevented hepatocyte lipid peroxidation. These findings suggest that oxidative membrane injury could be the result of TNF-alpha modulation of hepatocellular Ca2+ regulation during hemorrhage/resuscitation. FAU - Pizanis, A AU - Pizanis A AD - Department of Trauma, Hand and Reconstructive Surgery, University of Saarland, Homburg/Saar, Germany. FAU - Mutschler, W AU - Mutschler W FAU - Rose, S AU - Rose S LA - eng PT - Journal Article PL - Germany TA - J Mol Med (Berl) JT - Journal of molecular medicine (Berlin, Germany) JID - 9504370 RN - 0 (Antibodies, Monoclonal) RN - 0 (Tumor Necrosis Factor-alpha) RN - GAN16C9B8O (Glutathione) RN - SY7Q814VUP (Calcium) SB - IM CIN - J Mol Med (Berl). 1999 Jan;77(1):1-2. PMID: 9930919 MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Calcium/*metabolism MH - Glutathione/metabolism MH - Homeostasis MH - Lipid Peroxidation MH - Liver/cytology/*metabolism MH - Male MH - Oxidation-Reduction MH - Rats MH - Rats, Sprague-Dawley MH - Shock, Hemorrhagic/metabolism/*physiopathology MH - Tumor Necrosis Factor-alpha/immunology/*physiology EDAT- 1999/02/04 00:00 MHDA- 1999/02/04 00:01 CRDT- 1999/02/04 00:00 PHST- 1999/02/04 00:00 [pubmed] PHST- 1999/02/04 00:01 [medline] PHST- 1999/02/04 00:00 [entrez] AID - 10.1007/s001090050291 [doi] PST - ppublish SO - J Mol Med (Berl). 1999 Jan;77(1):8-13. doi: 10.1007/s001090050291.