Plasma F2-Isoprostane: A Biochemical Link Between Tissue Inflammation, Lipid Peroxidation and Cerebral Atherosclerosis in Uremic Children.

ABSTRACT
Background: Cerebral  atherosclerosis is a major contributing factor to the high prevalence of cerebrovascular mortalities in uremic children. Enhancement of lipid peroxidation (LPO), attributable mainly to inflammation, is an important risk factor for premature  atherosclerosis in chronic renal failure (CRF).  Plasma F2-Isoprostane may provide a quantitative index of LPO, thus it could be a link between inflammation, LPO and atherosclerosis in CRF. Objectives: This study aimed at investigation of LPO (measured by Plasma F2-Isoprostane) in relation to inflammation (indicated by C-reactive protein “CRP”) and Cerebral  atherosclerosis,  assessed by transcranial Doppler ultrasonography (TCD). In patients with (CRF).  In addition, the suppressive effect of Oral vitamin E antioxidant therapy on LPO, measured by Plasma F2-Isoprostane, was also investigated. Methods: Thirty-four patients with CRF (22 on regular hemodialysis “HD” and 12 on conservative management) were studied in comparison to 34 healthy children serving as controls. Beside clinical evaluation, assessment of plasma F2-Isoprostane (ELISA), CRP and cerebral circulation using TCD was done. Vitamin E was supplied orally to patients with high Plasma F2-Isoprostane levels (400 IU daily for two months) and re-estimation of Plasma F2-Isoprostane was done after completion of therapy. Results: Patients with CRF, either on regular HD or on conservative management, had significantly higher plasma F2-Isoprostane and CRP levels than healthy controls. Plasma F2-Isoprostane levels were elevated in 61.8% of CRP patients, There was a significant positive correlation between plasma F2-Isoprostane and CRP levels. Clinical neurological manifestations (such as transient ischemic attacks, convulsions, pyramidal weakness and peripheral neuritis) were found in 14 patients with CRF (41.2%).TCD abnormalities (impaired vasoreactivity “VR” ± flow abnormalities), which may point out to the presence of cerebral atherosclerosis, were found in 70.6% of CRF patients. These abnormalities were found in all patients with and in 50%of those without clinical neurological manifestations. There was a significant positive association between TCD abnormalities and both of Plasma F2-Isoprostane and CRP. In addition, vitamin E antioxidant therapy resulted in a significant decrease of Plasma F2-Isoprostane levels. Conclusions: LPO, measured by Plasma F2-Isoprostane, may be enhanced in uremic patients. This may be attributable to the inflammatory process of the disease. Both LPO and inflammation may be important factors contributing to premature Cerebral  atherosclerosis, assessed by TCD, in these patients. In addition vitamin E supplementation, as an antioxidant therapy, may result in suppression of the enhanced LPO in uremic patients. Wider scale studied investigating the suppressive effect of different regimens of vitamin E on LPO, measured by Plasma F2-Isoprostane, are warranted as this LPO marker may serve as an indicator for the effectiveness of antioxidant strategies in patients with CRF.