Ascorbic Acid Attenuates Acute Ethanol-Induced Liver Injury in SMP30 Knockout Mice

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.

Hepatic Protective Effects of <i>S</i>-Allyl-L-Cysteine (SAC) in Rats with Carbon Tetrachloride (CCl₄) Induced Liver Injury

S-allyl-L-cysteine (SAC) is an organosulfur compound derived from aged garlic extract (AGE). Studies have reported that AGE possesses bioprotective capacity, including antidiabetic, antimicrobial, antioxidant, and antitumor effects. The present study examined the protective effects of SAC against carbon tetrachloride (CCl4) induced hepatotoxicity in rats. Ten male Wistar rats aged 11 - 12 weeks were randomly divided into two groups (five rats/group) as control and SAC groups. All rats had ad libitum access to water, and the SAC group received water containing SAC intragastrically (200 mg/kg) once daily for five consecutive weeks. In the fifth experimental week, 50% CCl4 in olive oil (1 mL/kg) was administered intraperitoneally three times a week to induce liver injury in both groups. Rats were sacrificed at 24 hours after the last CCl4 injection, and liver tissues were excised for histopathological, immunohistochemical and antioxidant analyses. The rats in the SAC group did not show abnormal behavior, such as decreased water intake or food consumption, during the experimental period. Body weights in all groups did not change significantly over the experimental period. Histopathological analysis showed that the percentage of hepatic steatosis was lower in the SAC group at 12.75% ± 3.74% compared to 24.64% ± 5.29% in the control group (p < 0.05). The percentage of cytochrome P4502E1 (CYP2E1) distribution area in the SAC group was also lower at 19.61% ± 6.18% compared with 25.22% ± 6.21% in the control group (p < 0.05). These results suggest that SAC can alleviate CCl4-induced liver damage by decreasing hepatic steatosis and reducing CYP2E1 expression in rats.