Protective role of dehydroascorbate in rat liver ischemia-reperfusion injury.
BACKGROUND
Oxidative stress plays an important role in liver ischemia/reperfusion (I/R) injury. Thus, enhancing the liver antioxidant capacity could be a promising therapeutic strategy. Ascorbate (AA) is considered the perfect antioxidant, but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administering dehydroascorbate (DHA), which presents a several-fold greater uptake than AA, and undergoes rapid intracellular reduction to AA. Thus, our aim was to assess the protective role of DHA in liver I/R injury.


METHODS
Wistar rats (200-300 g bw) were pretreated iv with different doses of AA or DHA 20 min before liver ischemia, followed by 6 h reperfusion. Liver damage was assessed by biochemical and morphological indices.


RESULTS
DHA pretreatment induced a rapid increase in liver ascorbate levels, significantly higher than findings for AA, without any significant reduction in glutathione levels. Liver damage during I/R in controls showed significant increases in serum transaminases and hepatic thiobarbituric acid reactive substances with alterations of liver morphology. DHA administration induced a clear, significant protection against I/R injury, whereas liver damage was only moderately prevented by AA.


CONCLUSIONS
DHA might represent a simple, effective therapeutic option to prevent liver damage associated with ischemia/reperfusion.
De Tata
Vincenzo
V
Department of Experimental Pathology, Medical Biotechnologies, Infectivology and Epidemiology, University of Pisa, Pisa, Italy. v.detata@ipg.med.unipi.it
Brizzi
Stefania
S
Saviozzi
Michela
M
Lazzarotti
Alessandra
A
Fierabracci
Vanna
V
Malvaldi
Gino
G
Casini
Alessandro
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid