Fig. 5.

Ischemia-induced oxidation of DNA and protection by MnTE-2-PyP⁵⁺. Rats were treated with intracerebroventricular MnTE-2-PyP⁵⁺ (300 ng) or vehicle at 5 min or 6 hr after onset of reperfusion from 90 min middle cerebral artery occlusion (n = 6–8 per condition). Brains were sampled at 4 hr after treatment, respectively (n = 6–8 per condition). The ratio of 8-hydroxy-2′-deoxyguanosine (8-OHdG) to 2′-deoxyguanosine (dG) was determined in cortical tissue 4 hr after drug–vehicle treatment. There was no effect of MnTE-2-PyP⁵⁺ in the nonischemic hemisphere at either study interval. Ischemia increased the 8-OHdG/dG ratio nearly threefold at 4 hr, and this persisted at 10 hr after ischemia (see vehicle-treated groups). Treatment with MnTE-2-PyP⁵⁺reduced the ischemic 8-OHdG/dG ratio by 39% (p = 0.003) when given 5 min after reperfusion and by 21% when given 6 hr after ischemia. At both treatment intervals, the ratio in the ischemic hemisphere of MnTE-2-PyP⁵⁺-treated rats remained greater than in the respective nonischemic hemisphere. a, Difference between ischemic and nonischemic hemisphere (p ≤ 0.02); b, difference between treatment vehicle and MnTE-2-PyP⁵⁺ groups in the ischemic hemisphere (p < 0.05). Values represent mean ± SD.