Dietary glycine decreases liver injury after haemorrhagic shock in rats

Abstract

Abstract Background Resuscitation from haemorrhagic shock induces profound changes in the physiological processes of the liver and activates inflammatory cascades that include activation of stress transcriptional factors and upregulation of tumour necrosis factor (TNF) synthesis. This process is accompanied by increased levels of free radicals that may contribute to acute organ damage. Intravenous administration of glycine, a simple amino acid, has been reported to decrease release of TNF and to improve the survival rate of rats after haemorrhagic shock or endotoxin administration. The effects of feeding a glycine-containing diet (5 per cent) on liver injury and on the oxidant–antioxidant balance in resuscitated haemorrhagic rats has been investigated. Methods Rats were bled to maintain mean arterial pressure at 30–35 mmHg for 1 h and subsequently resuscitated with 60 per cent shed blood and lactate Ringer's solution. Thiobarbituric acid reactive substances (TBARS) and the oxidized: reduced glutathione (GSSG: GSH) ratio were measured as markers of oxidative stresss. The activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) were determined in liver cytosol. Results Levels of aspartate aminotransferase (ASAT) were increased 22-fold and levels of alanine aminotransferase (ALAT) eightfold 20 h after resuscitation. Leucocyte infiltration and pericentral necrosis were also observed. Serum nitrite concentration increased by 69 per cent. Liver TBARS increased by 32 per cent and the GSSG: GSH ratio by 106 per cent. There was a significant reduction in total liver glutathione concentration (−42 per cent) and in the activities of SOD (−23 per cent), GPx (−26 per cent) and Cat (−46 per cent). Serum nitrite, liver TBARS concentration and the antioxidant enzyme activities remained unchanged in animals receiving dietary glycine. The GSSG: GSH ratio and total glutathione concentration did not significantly differ from control values. The increase in serum ASAT and ALAT levels and in hepatic necrosis were markedly reduced. Conclusion Dietary glycine prevents liver injury caused by haemorrhagic shock in the rat. Diminished availability of nitric oxide and maintenance of the oxidant–antioxidant balance may reduce the pathophysiological sequelae of severe haemorrhage.