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Effect of methylprednisolone on plasma lipid peroxidation induced by lipopolysaccharide
T Kouno1, T Egashira, F Takayama
1Department of Pharmacology, Oita Medical University, Japan.
Abstract:
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.
Insights
Methylprednisolone succinate (MP) reduces lipid peroxidation and superoxide production in rats. This steroid suppresses inflammation markers like phosphatidylcholine hydroperoxide (PCOOH) and superoxide generation in polymorphonuclear leukocytes (PMNs).
Area of Science:
- Biochemistry
- Pharmacology
- Immunology
Background:
- Lipopolysaccharide (LPS) induces oxidative stress, increasing plasma lipid peroxidation and decreasing superoxide dismutase (SOD) activity.
- Polymorphonuclear leukocytes (PMNs) play a role in LPS-induced inflammation.
- Methylprednisolone succinate (MP) is a corticosteroid with known anti-inflammatory properties.
Purpose of the Study:
- To investigate the effects of MP on LPS-induced oxidative stress markers in rats.
- To determine the impact of MP on plasma lipid peroxidation, SOD activity, and PMN superoxide production.
- To elucidate the mechanism by which MP exerts its protective effects against oxidative damage.
Main Methods:
- In vivo studies in rats treated with LPS and MP.
- In vitro experiments assessing MP's effects on lipid peroxidation and superoxide production in PMNs.
- Measurement of plasma phosphatidylcholine hydroperoxide (PCOOH) levels and Cu,Zn-SOD activity.
- Assessment of superoxide production in PMNs stimulated by phorbol 12-myristate 13-acetate (PMA).
Main Results:
- LPS treatment significantly increased plasma PCOOH and decreased plasma Cu,Zn-SOD activity.
- MP administration suppressed the elevation of plasma PCOOH and partially inhibited the decrease in Cu,Zn-SOD activity.
- MP suppressed PMA-induced superoxide production in LPS-primed PMNs.
- In vitro, high MP concentrations inhibited NADPH-dependent lipid peroxidation, but MP showed no radical-trapping effects.
Conclusions:
- MP effectively suppresses LPS-induced plasma lipid peroxidation and oxidative stress in rats.
- The anti-oxidative effect of MP may involve inhibiting lipid chain reactions rather than direct radical scavenging.
- MP's mechanism may involve modulating superoxide anion generation by PMNs in inflammatory conditions.