Anti-hypoxia Activity of the Novel NO Donor Acetyl Ferulic Isosorbide Mononitrate in Acute High-Altitude Hypoxia Mice.
Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H2O2 in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.
Department of Pharmacy, General Hospital of Lanzhou Command of PLA.
Peng-Cheng
PC
Fan
Hui-Ping
HP
Ma
Wei
W
Jiang
Lin
L
Li
Jun
J
Ren
Lin-lin
LL
Jing
Zheng-Ping
ZP
Jia
D000255:Adenosine Triphosphate / Q000378:metabolism; D000532:Altitude Sickness / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008315:Malondialdehyde / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D020030:Nitric Oxide Donors; C547606:acetyl ferulaic isosorbide; D019344:Lactic Acid; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D007548:Isosorbide Dinitrate