Toshiaki Kato

Plant lycopene exhibits antioxidant activity in animal tissues. Transient cerebral ischemia/reperfusion in Mongolian gerbils resulted in delayed neuronal death in hippocampal regions. We examined the antioxidant effects of lycopene because we expected lycopene to attenuate ischemia-related neuronal damage by controlling apoptosis at the gene level. The gerbils were divided into two groups: the normal feeding (control) group that received normal market food (MF) and the lycopene group that received MF containing lycopene (5 mg in 100 g MF food). After 1.5-2.0 months (when body weight were 60-65 g), the lycopene level was 38.2 +/- A 17.6 ng/ml in serum and 11.9 +/- A 4.0 mu g/g-wet weight tissue in the liver. Levels of B cell leukemia-2, an apoptosis-suppressing protein, decreased in control animal brains 1, 3, and 7 days after surgery, whereas the levels increased in lycopene-treated animal brains. Moreover, cysteinyl aspartate-specific protease-3 activity increased gradually after ischemia, but was suppressed in the lycopene-treated animal brains 7 days after surgery. Finally, hippocampal superoxide dismutase (SOD) activity decreased in the control group 3 h after ischemia and, gradually increased thereafter, whereas it was significantly elevated in the lycopene group. Thus, orally administered lycopene is accumulated in the body, and provided protections against ischemia/reperfusion-induced brain injury by inducing an increase in SOD activity and inhibiting apoptosis.

We analyzed the protective effect of 17 beta-estradiol (17 beta-ED) injection against delayed neuronal death in the hippocampus tissue of the brain in Mongolian gerbils after transient ischemia/recirculation treatment, especially in relation with bcl-2 gene expression and enzymatic activity changes of caspase-3 and tissue transglutaminase (tTGase). Daily intraperitoneal injection of 17 beta-ED to the animal after the ischemia stimulated the expression of an apoptosis suppressor gene, bcl-2, in the hippocampal tissue for a week. The gradually increasing apoptotic enzyme activity of caspase-3 and increased number of TUNEL positive fragmented neuronal nuclei caused by ischemic attack in the gerbil brain were clearly suppressed by 17 beta-ED administration. The reduced activity and enzyme protein of tTGase, a neurodegenerative marker of apoptosis in the hippocampus after ischemia, were also restored to nearly normal levels by 17 beta-ED injection. These results suggest that daily 17 beta-ED administration to the gerbil after transient ischemic insult with progressing neuronal deteriorative changes in hippocampus tissue can effectively prevent apoptotic changes through a molecular cascade involving gene expression regulation.