Kaempferol protects against rat striatal degeneration induced by 3-nitropropionic acid.
3-Nitropropionic acid (NPA) produces degeneration of striatum and some neurological disturbances characteristic of Huntington's disease in rodents and primates. We have shown that the flavonoid kaempferol largely reduced striatal damage induced by cerebral ischaemia-reperfusion in rats (Lopez-Sanchez et al. 2007). In this work, we report that intraperitoneal (i.p.) administration of kaempferol affords an efficient protection against NPA-induced neurodegeneration in Wistar rats. We studied the effects of daily i.p. injections of 7, 14 and 21 mg of kaempferol/kg body weight during the NPA-treatment (25 mg/kg body weight/12 h i.p., for 5 days) on the neurological deficits, degeneration of rat striatum and oxidative stress markers. Intraperitoneal injections of 14-21 mg of kaempferol/kg body weight largely attenuated motor deficit and delayed mortality. The higher dose of kaempferol prevented the appearance of NPA-induced striatal lesions up to the end of treatment, as revealed by haematoxylin-eosin and TUNEL staining, and also NPA-induced oxidative stress, because it blocked the fall of reduced glutathione and the increase of protein nitrotyrosines in NPA-treated rats. It was found that striatal degeneration was associated with calpains activation and a large inactivation of creatine kinase, which were also prevented when the higher doses of kaempferol were administered.
Lagoa
Ricardo
R
Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.
Lopez-Sanchez
Carmen
C
Samhan-Arias
Alejandro K
AK
Gañan
Carlos M
CM
Garcia-Martinez
Virginio
V
Gutierrez-Merino
Carlos
C
D000818:Animals; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000188:drug therapy; D044949:Kaempferols / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D003292:Convulsants; D044949:Kaempferols; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C006552:kaempferol; D003402:Creatine Kinase; D002154:Calpain; D020169:Caspases; C015392:3-nitropropionic acid