Kouno T, Egashira T, Takayama F, Kudo Y, Yamanaka Y
Department of Pharmacology, Oita Medical University, Japan.
Jpn J Pharmacol. 1994 Mar;64(3):163-9. doi: 10.1254/jjp.64.163.
The effects of methylprednisolone succinate (MP) on plasma lipid peroxidation, plasma SOD activity and superoxide production in polymorphonuclear leukocytes (PMNs) induced by lipopolysaccharide (LPS) were examined in rats in vivo and in vitro. In rats subjected to LPS treatment, plasma phosphatidylcholine hydroperoxide (PCOOH) levels significantly increased, and the plasma Cu,Zn-SOD activity decreased by about 75%. When rats were given 30 mg/kg of MP intravenously, MP suppressed the elevation of plasma PCOOH levels and partially inhibited the decrease in plasma Cu,Zn-SOD activity. MP also suppressed PMA-induced superoxide production in PMNs primed by LPS. In in vitro experiments, low concentrations of MP had no effect on NADPH-dependent lipid peroxidation, but 4 mM MP produced 50% inhibition. MP had little effect on PMA-induced superoxide production in PMNs primed by LPS. Moreover, MP had no radical-trapping effect on superoxide, hydroxyl radical and stable DPPH radical. These results suggest that the suppressive effect of plasma lipid peroxidation by MP is not due to radical-trapping effects or preventive anti-oxidation, but may involve the suppression of the lipid chain reaction in liver membrane resulting from PMA-induced superoxide anions generated by PMNs.
在体内和体外实验中，研究了琥珀酸甲泼尼龙（MP）对脂多糖（LPS）诱导的大鼠血浆脂质过氧化、血浆超氧化物歧化酶（SOD）活性及多形核白细胞（PMN）中超氧化物生成的影响。接受LPS处理的大鼠，血浆磷脂酰胆碱氢过氧化物（PCOOH）水平显著升高，血浆铜锌超氧化物歧化酶活性降低约75%。当给大鼠静脉注射30mg/kg的MP时，MP可抑制血浆PCOOH水平的升高，并部分抑制血浆铜锌超氧化物歧化酶活性的降低。MP还可抑制由LPS致敏的PMN中佛波酯（PMA）诱导的超氧化物生成。在体外实验中，低浓度的MP对NADPH依赖性脂质过氧化无影响，但4mM的MP可产生50%的抑制作用。MP对由LPS致敏的PMN中PMA诱导的超氧化物生成影响不大。此外，MP对超氧化物、羟基自由基和稳定的二苯基苦味酰基自由基没有自由基捕获作用。这些结果表明，MP对血浆脂质过氧化的抑制作用不是由于自由基捕获作用或预防性抗氧化作用，而是可能涉及对PMN产生的PMA诱导的超氧阴离子所导致的肝细胞膜脂质链反应的抑制。
