Abstract
Retinoids influence the pathogenesis of alcohol liver disease (ALD). To analyze the impact of retinoid X receptor alpha (RXRα) on ALD, alcohol-induced hepatotoxicity was studied using mice fed ethanol intragastrically for 25 days. Alcohol-induced microvesicular fat around the central vein and drug-induced morphological changes (loss of rough endoplasmic reticulum, pinkish cytoplasm, and enlarged hepatocyte) in the pericentral area were observed in the liver of wild-type mice. In the hepatocyte RXRα-deficient mouse liver, alcohol induced fat accumulation, mitosis, acute inflammation, and necrosis. The histology score after alcohol treatment was significantly higher in mutant mice than in wild-type mice. However, drug-induced morphological changes were not apparent in alcohol-treated hepatocyte RXRα-deficient mice. Northern analysis showed that the basal and alcohol-induced CYP2B, CYP2A, and CYP3A mRNA levels were lower in hepatocyte RXRα-deficient mice than in wild-type mice, which in turn may protect mutant mice from morphological changes. Compared with wild-type mice, hepatocyte RXRα-deficient mice have significant lower levels of S-adenosylmethionine and glutathione, which is further reduced after alcohol treatment, and that may account for severe liver injury induced by alcohol. The overall result suggests an important role of RXRα in preventing alcohol-induced liver injury.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 194-200 |
| Number of pages | 7 |
| Journal | Experimental and Molecular Pathology |
| Volume | 75 |
| Issue number | 3 |
| DOIs | |
| State | Published - Dec 2003 |
Fingerprint
Keywords
- Alcohol
- Alcoholic liver disease
- Glutathione
- Retinoid X receptor alpha
- S-Adenosylmethionine
ASJC Scopus subject areas
- Clinical Biochemistry
- Molecular Biology
- Pathology and Forensic Medicine
Cite this
RXRα-regulated liver SAMe and GSH levels influence susceptibility to alcohol-induced hepatotoxicity. / Dai, Tiane; Wu, Yong; Leng, Ai She; Ao, Yan; Robel, Rose C V; Lu, Shelly C.; French, Samuel W.; Wan, Yu-Jui Yvonne.
In: Experimental and Molecular Pathology, Vol. 75, No. 3, 12.2003, p. 194-200.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RXRα-regulated liver SAMe and GSH levels influence susceptibility to alcohol-induced hepatotoxicity
AU - Dai, Tiane
AU - Wu, Yong
AU - Leng, Ai She
AU - Ao, Yan
AU - Robel, Rose C V
AU - Lu, Shelly C.
AU - French, Samuel W.
AU - Wan, Yu-Jui Yvonne
PY - 2003/12
Y1 - 2003/12
N2 - Retinoids influence the pathogenesis of alcohol liver disease (ALD). To analyze the impact of retinoid X receptor alpha (RXRα) on ALD, alcohol-induced hepatotoxicity was studied using mice fed ethanol intragastrically for 25 days. Alcohol-induced microvesicular fat around the central vein and drug-induced morphological changes (loss of rough endoplasmic reticulum, pinkish cytoplasm, and enlarged hepatocyte) in the pericentral area were observed in the liver of wild-type mice. In the hepatocyte RXRα-deficient mouse liver, alcohol induced fat accumulation, mitosis, acute inflammation, and necrosis. The histology score after alcohol treatment was significantly higher in mutant mice than in wild-type mice. However, drug-induced morphological changes were not apparent in alcohol-treated hepatocyte RXRα-deficient mice. Northern analysis showed that the basal and alcohol-induced CYP2B, CYP2A, and CYP3A mRNA levels were lower in hepatocyte RXRα-deficient mice than in wild-type mice, which in turn may protect mutant mice from morphological changes. Compared with wild-type mice, hepatocyte RXRα-deficient mice have significant lower levels of S-adenosylmethionine and glutathione, which is further reduced after alcohol treatment, and that may account for severe liver injury induced by alcohol. The overall result suggests an important role of RXRα in preventing alcohol-induced liver injury.
AB - Retinoids influence the pathogenesis of alcohol liver disease (ALD). To analyze the impact of retinoid X receptor alpha (RXRα) on ALD, alcohol-induced hepatotoxicity was studied using mice fed ethanol intragastrically for 25 days. Alcohol-induced microvesicular fat around the central vein and drug-induced morphological changes (loss of rough endoplasmic reticulum, pinkish cytoplasm, and enlarged hepatocyte) in the pericentral area were observed in the liver of wild-type mice. In the hepatocyte RXRα-deficient mouse liver, alcohol induced fat accumulation, mitosis, acute inflammation, and necrosis. The histology score after alcohol treatment was significantly higher in mutant mice than in wild-type mice. However, drug-induced morphological changes were not apparent in alcohol-treated hepatocyte RXRα-deficient mice. Northern analysis showed that the basal and alcohol-induced CYP2B, CYP2A, and CYP3A mRNA levels were lower in hepatocyte RXRα-deficient mice than in wild-type mice, which in turn may protect mutant mice from morphological changes. Compared with wild-type mice, hepatocyte RXRα-deficient mice have significant lower levels of S-adenosylmethionine and glutathione, which is further reduced after alcohol treatment, and that may account for severe liver injury induced by alcohol. The overall result suggests an important role of RXRα in preventing alcohol-induced liver injury.
KW - Alcohol
KW - Alcoholic liver disease
KW - Glutathione
KW - Retinoid X receptor alpha
KW - S-Adenosylmethionine
UR - http://www.scopus.com/inward/record.url?scp=0242594507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242594507&partnerID=8YFLogxK
U2 - 10.1016/S0014-4800(03)00091-1
DO - 10.1016/S0014-4800(03)00091-1
M3 - Article
C2 - 14611810
AN - SCOPUS:0242594507
VL - 75
SP - 194
EP - 200
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
IS - 3
ER -