Protective effect of antioxidant ebselen (PZ51) on the cerebral cortex of stroke-prone spontaneously hypertensive rats.
An increase in reactive oxygen species has been shown to play a role in perpetuating hypertension and cerebral injury in stroke-prone spontaneously hypertensive rats (SHRsp). Lipid peroxidation in the cerebral cortex is much more intense in SHRsp after establishment of severe hypertension as compared to that in normotensive Wistar-Kyoto rats (WKY). Cortical neurons from SHRsp are more vulnerable to hypoxia and hyponutritional conditions. We sought to investigate whether long-term administration of seleno-glutathione peroxidase mimic ebselen (PZ51) would have a protective effect on cortical neurons in SHRsp, and, if so, the possible mechanisms of this effect. Twenty-two 8-week-old SHRsp were randomized into a PZ51 group and control group. Age-matched WKY were used as normal controls. We examined the levels of malonaldehyde (MDA) and nitric oxide (NO) in the cerebral cortex (CC) homogenate, detected the three isoforms of nitric oxide synthase (NOS) by Western blotting, and examined cortical neurons by transmission electron microscopy. The results showed that PZ51 treatment significantly decreased both MDA and NO in the CC, inhibited inducible nitric oxide synthase (iNOS) protein expression, and alleviated the damage to cortical neurons compared to the findings for the control group. In conclusion, the present study showed that PZ51 administration suppressed lipid peroxidation and inhibited iNOS protein expression in CC homogenate, and it was suggested that these mechanisms may play a role in the protective effects of PZ51 on cortical neurons of SHRsp.
Sui
Hui
H
Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No167 BeiLishi Road, Xicheng District, Beijing 100037, P.R. China. suihuipumc@sina.com
Wang
Wen
W
Wang
Pei He
PH
Liu
Li Sheng
LS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001794:Blood Pressure; D015153:Blotting, Western; D001835:Body Weight; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D054833:Isoindoles; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000517:prevention & control*
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D009419:Nerve Tissue Proteins; D016566:Organoselenium Compounds; D009569:Nitric Oxide; C042986:ebselen; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat