Moderate hypothermia(MH30) is more effective than mild hypothermia(MH34) at preventing increases in lipid peroxidation(LP) but equally effective at preventing increases in vascular resistance(VR)

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(1 INCREASED SUPEROXIDE GENERATION IS ASSOCIATED WITH DECREASED SUPEROXIDE DISMUTASE ACTIVITY IN TROPHOBLASTS FROM PREECLAMPSIA. Yuoine Wang, Department of Obstetrics and Gynecology, LSUMC, Shreveport, LA 71130 Preeclampsia (PE) is a multi-system disorder unique to human pregnancy. Although the etiology of PE is unknown, increased placental oxidative stress is important in the pathophysiology of PE. The goal of this study was to determine if trophoblast cells (TC) generate more superoxides (-O,*) and if superoxide dismutase (SOD) activity is deficient in TC from PE placentas as compared to TC from normal (Nor) placentas. Placentas were obtained from 8 Nor and 10 PE pregnancies immediately after delivery. TC were isolated and purified by Percoll gradient centrifugation. -0,. generation and SOD activity were assayed. Total RNA was extracted and mRNA expression of CuZnSOD was determined by Northern blot analysis. 18s ribosomal RNA was used as an internal standard. Statistical analysis was performed with Student’s t-test and Mann-Whitney U test. Results: 1) TC from PE placentas generated significantly more -0,. than TC from Nor placentas: 17.62k3.19 vs. 4.7OkO.76 nmol/5x106 cells (mean&.E.), P
Premature aging disease Progeria has the altered levels of primary antioxidant enzymes Tao Yan Xiaohong Jiang, Shijun Li, and Larry W. Oberley Radiation Research Laboratory, The University of Iowa, Iowa City, IA 52242 Free radical may play a central role in aging process. The profile of primary antioxidant enzymes (AE) that scavenge reactive oxygen species (ROS) was examined in this study in human skin fibroblasts from progeria. Compared with normal control cells, basal level of MnSOD as well as the induction of MnSOD expression in response to chronic stress were decreased in progeria cells, CuZnSOD showed no progeria-related change. Two Hz02 removing enzymes demonstrated a significant reduction in progeria cells. Catalase is reduced by 50% and glutathione peroxidasel by 70%. This altered AE profile may lead to an imbalance of intracellular ROS, and further lead to a changed oxidative stress level. Therefore, diminished Hz02 removing capacity may play an important role in the development of progeria. The decreased MnSOD level may also contribute to this process.

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MODERATE HYPOTHERMIA(MH30) IS MORE EFFECTIVE THAN MILD HYPOTHERMIA(MH34) AT PREVENTING INCREASES IN LIPID PEROXIDATION BUT EQUALLY EFFECTIVE AT PREVENTING INCREASES IN VASCULAR RESISTANCE(VR). Harvey Zar and Daelim Jee. U.of North Carolina. Hypothermia is routinely used in medicine to protect against ischemic injury. The mechanisms of hypothermic protection have not been well studied. We have shown previously that MH34 decreases reperfusion oxygen free radical formation, LP and postischemic increases in VR. In this investigation, we used chemiluminescence (CL) as a measure of LP to study if MH30 would be more effective than MH34 in decreasing reperfusion LP and postischemic increases in VR in a perfused rat liver model. Livers, perfused with a modified Krebs Henseleit solution were exposed to 2.5 h of ischemia

and 2h of reperfusion

at 3OoC, 34’C

or normothermia(NT), 38oC. CL and hepatic vascular resistance were monitored simultaneously. CL increased in the NT group at 60-120 min of reperfusion. MH34, CL was only increased at 120 min but less than for NT. CL was unchanged MH30. VR increased in the NT group at 60-120 min of reperfusion. VR only increased at 0 min for MH34 and not at all for MH30. At 120 min, VR was not different between MH34 and MH30. MH30 is more effective than MH34 at preventing increases in LP but equally effective at preventing increases in VR. The cost of either therapy must be weighed against the benefits.

OXYGEN

ETHANOL INDUCES HEPATIC LIPID PEROXIDATION THROUGH INTERLEUKIN-6 IN MICE Jill Pete Smith, Evan T. Keller. Unit Lab. v ‘. Murtha, Paula Habib, Animnl ediczne, Dept.Pnthology and Inst. Gerontology, U. of Michigan, Ann

Arbor,

MI 48109.0940

 Alcohol-induced oxidative stress leading to hepatic inflammation may be a key factor in the development of hepatic cirrhosis. Pro-inflammatory cytokines such as interleukin-6 (IL-6) promote radical formation. Accordingly, we hypothesized that alcohol induces hepatic oxidative stress through induction of interleukin-6 expression. To explore this hypothesis, wildtype and IL-6 gene knockout 6-month-old female C57B1/6 mice were fed a 4% (v/v) ethanol diet for 2 weeks. Parallel sets of gene knockout and wildtype mice were pair-fed a control diet. At the end of 2 weeks, the mice were sacrificed and the liver collected for evaluation of malonaldehyde (MDA). Hepatic MDA levels were elevated by approximately 20% in the alcohol-fed vs. control diet-fed wildtype mice. In contrast, hepatic MDA levels were decreased by approximately 30% in the alcohol-fed IL-6 gene knockout mice vs. the control-fed wildtype or control-fed IL-6 gene knockout mice. Thus, the hepatic MDA levels in the alcohol-fed IL-6 gene knockout mice were approximately 50% lower than those of the alcohol-fed wildtype mice. To further determine if oxidative stress induces hepatic IL-6 expression, we incubated hepatic tissue from mice that were transgenic for the IL-6 promoter driving the luciferase gene with hydrogen peroxide (1, 10,100,1000 uM). Luciferase activity was increased over 100-fold at 100 uM. These data demonstrate that alcohol-induced hepatic MDA depends, in part, on IL-6. Furthermore, they suggest that alcohol-induced oxidative stress stimulates IL-6 expression. We conclude that oxidative stress-mediated IL-6 expression may be a contributing factor to alcohol-induced hepatic cirrhosis. This work was supported by NIA R01 AG15904.

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