THE EFFECT OF NORDIHYDROGUAIARETIC ACID ON LEUKOTRIENE-C(4) AND PROSTAGLANDIN-E(2) PRODUCTION FOLLOWING DIFFERENT REPERFUSION PERIODS IN RAT-BRAIN AFTER FOREBRAIN ISCHEMIA CORRELATED WITH MORPHOLOGICAL-CHANGES

Leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) are the 5-lipoxygena se and cyclooxygenase metabolites of arachidonic acid (AA). They const rict blood vessels and enhance vascular permeability inducing vasogeni c edema that may hurt the ischemic penumbra after cerebral ischemia an d reperfusion. Nordihydroguaiaretic acid (NDGA) is known as the most p otent inhibitor of 5-lipoxygenase in different tissues. Furthermore, i t has considerable inhibitory activity against cyclooxygenase. In this study, after developing a global ischemic model in the rat, the level s of LTC4 and PGE2 in the forebrain were measured, following different reperfusion periods after 10 min ischemia including 8 rats for each r eperfused group. Sham operations were performed for each corresponding control group (n = 8). AA metabolites were then correlated with neuro pathological findings. In the combined reperfused groups both metaboli tes increased significantly when compared with 10 min, ischemic group (P < 0.05). In the 8 min reperfused group, PGE2 and LTC4 increased sig nificantly compared with each corresponding control group (P < 0.005). These mediators also increased to high levels compared with the 4 min reperfused group (P < 0.05, P < 0.005). PGE2 and LTC4 were reduced si gnificantly at the 15th and 60th min of reperfusion compared with the 8 min reperfused group (P < 0.05, P < 0.005). NDGA (0.1 mg/kg) reduced both metabolites in the 8 min reperfused group significantly (P < 0.0 5). Brain cortex specimens were taken for light and electromicroscopic al investigations. No significant differences were noted between the s tructural changes in the 4, 8 and 15 min of reperfusion and NDGA admin istered groups. Widenings of subendothelial spaces around capillaries and degeneration of neurons were seen at the 60th min of reperfusion w hereas similar but lesser changes was observed at 60 min in the NDGA-a dministered animals. In conclusion, NDGA reduced LTC4 as well as PGE2 at a dosage of 0.1 mg/kg following 8 min reperfusion. It may be helpfu l in protecting the ischemic penumbra in the early min of reperfusion by reducing the formation of both 5-lipoxygenase and cyclooxygenase me tabolites.