TITLE:
Ascorbic Acid Attenuates Acute Ethanol-Induced Liver Injury in SMP30 Knockout Mice
AUTHORS:
Eun-Mi Cho, H. M. Arif Ullah, Ahmed K. Elfadl, Myung-Jin Chung, Soong-Koo Kim, Yong Deuk Kim, Eun-Joo Lee, Kyu-Shik Jeong
KEYWORDS:
Ascorbic Acid, Alcohol, Liver, SMP30
JOURNAL NAME:
Food and Nutrition Sciences,
Vol.8 No.12,
December
19,
2017
ABSTRACT: Ascorbic acid (AA) is recognized as a free radical scavenger that protects cells
from oxidative stress-induced damage. However, no studies have investigated
the role of AA in acute alcoholic liver disease using senescence marker protein-30 (SMP30) knockout (KO) mice. SMP30 is a novel 34-kDa protein involved
in AA biosynthesis. The present study aimed to elucidate the physiological
functions of AA in acute ethanol-induced liver injury using SMP30 KO
mice, which cannot synthesize AA in vivo. After a 4-week experimental period,
mice were divided into six groups. The following three groups comprised
the ethanol treatment groups: WT-E group (wild-type), KV-E group
(AA-supplemented), and KT-E group (AA-deficient). Mice were exposed to
an acute dose of ethanol (6 g ethanol/kg) administered by gavage once a day
for three days. The other three control groups, namely, WT-C, KV-C, and
KT-C control groups, received an equal volume of water via oral administration.
Analysis of changes in body weight showed that mice in the KT-E group
had significant loss of body weight compared to the control, KV-E, and WT-E
groups. Behavioral analysis revealed that alcohol exposure significantly increased
alcohol sensitivity in the KT-E group, whereas the WT-E, KV-E, and
control groups developed ethanol tolerance. Aspartate transaminase (AST)
levels in the KT-E group were significantly higher than those in the control,
KV-E, and WT-E groups. The number of large and binucleated hepatocytes
was significantly higher in the KT-E group than in the KV-E and WT-E
groups. In addition, cytochrome P450 2E1 (CYP2E1) was over expressed in
the central vein in the KT-E group when compared to the KV-E and WT-E
groups. Our current findings indicate that AA supplementation in SMP30 KO
mice can alleviate alcohol-induced liver damage by down regulating CYP2E1
expression. These results suggest that reduced CYP2E1 expression is a novel mechanism responsible for AA-induced reduction of ethanol-mediated oxidative
stress.