Brain damage following subarachnoid hemorrhage: the imbalance between anti-oxidant systems and lipid peroxidative processes.
We have studied the pattern of enzymatic antioxidant activities (Cu-Zn superoxide dismutase = SOD, Mn-SOD and glutathione peroxidase = GSH-Px) in brain cortex of rats subjected to experimental induction of subarachnoid hemorrhage (SAH), in order to discuss the modifications of antioxidant systems in relation to the development of lipid peroxidative processes occurring in brain cortex. Lipid peroxidation (quantified as TBRAs content) did not show significantly changes, when sham-operated and SAH rats were compared; meanwhile at 1 hour TBARs content shows an increasing trend both in sham-operated and hemorrhagic rats. The release of leukotriene C4, the major lipoxygenase metabolite, is significantly enhanced at 1, 6 and 48 hours after SAH induction. Cu-Zn SOD activity is significantly reduced at 6 and 48 hours after SAH induction; Mn-SOD activity is significantly affected at 1, 6 and 48 hours after the hemorrhage. GSH-Px activity is significantly reduced only in the late phase (48 hours) after SAH. The results of the present study suggests that: (a) in brain compartment a significant reduction of antioxidant enzymatic activities is related to the increasing trend of enzymatic lipid peroxidation; (b) antioxidant activities showed specific time-dependent modifications: Cu-Zn and Mn SOD activities, which are specific scavengers of superoxide radicals, showed an early impairment, while GSH-Px activity is significantly reduced only after 48 hours; (c) the enhancement of enzymatic lipid peroxidation via the lipoxygenase pathway seems to play a primary role in brain response to SAH. These results should be considered the rationale for pharmacological treatment with antioxidant compounds for brain protection against detrimental effects of subarachnoid hemorrhage.
Gaetani
P
P
Department of Surgery, Neurosurgery, IRCCS Policlinico S. Matteo, University of Pavia, Italy.
Lombardi
D
D
D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000517:prevention & control; D015227:Lipid Peroxidation; D008084:Lipoxygenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism*
D013189:SRS-A; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D008084:Lipoxygenase; D013482:Superoxide Dismutase