Lipoic acid protects gastric mucosa from ethanol-induced injury in rat through a mechanism involving aldehyde dehydrogenase 2 activation.
Numerous studies demonstrate that reactive aldehydes are highly toxic and aldehyde dehydrogenase 2 (ALDH2)-mediated detoxification of reactive aldehydes is thought as an endogenous protective mechanism against reactive aldehydes-induced cell injury. This study aims to explore whether lipoic acid, a potential ALDH2 activator, is able to protect gastric mucosa from ethanol-induced injury through a mechanism involving clearance of reactive aldehydes. The rats received 60% of acidified ethanol through intragastric administration and held for 1 h to establish a mucosal injury model. Lipoic acid (10 or 30 mg/kg) or Alda-1 (a positive control, 10 mg/kg) was given 45 min before the ethanol treatment. The gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) contents, and ALDH2 activity. The results showed that acute administration of ethanol led to an increase in gastric ulcer index, cellular apoptosis, 4-HNE and MDA contents concomitant with a decrease in ALDH2 activity; these phenomena were reversed by lipoic acid or Alda-1. The gastric protection of lipoic acid was attenuated in the presence of ALDH2 inhibitor. Based on these observations, we conclude that lipoic acid exerts the beneficial effects on ethanol-induced injury through a mechanism involving, at least in part, ALDH2 activation. As a dietary supplement or a medicine already in some countries, lipoic acid can be used to treat the ethanol - induced gastric mucosal injury.
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Jia-Hui
JH
Li
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Gui-Xia
GX
Ju
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Jun-Lin
JL
Jiang
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Nian-Sheng
NS
Li
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. Electronic address: junpeng@csu.edu.cn.
Jun
J
Peng
Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China. Electronic address: xjluo22@csu.edu.cn.
Xiu-Ju
XJ
Luo
D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*
D000431:Ethanol; D008063:Thioctic Acid; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat
4-Hydroxy-2-nonenal; Aldehyde dehydrogenase 2; Ethanol; Gastric mucosa; Lipoic acid