Tokyay R

L-glutamine enemas attenuate mucosal injury in experimental colitis

PURPOSE: The aim of this study was to investigate the role of I-glutamine, short chain fatty acid, prednisolone, and mesalazine (5-aminosalicylic acid) enemas on mucosal damage and inflammation in experimental colitis. METHODS: Colitis was induced in rats with trinitrobenzene sulfonic acid in ethanol. Saline (n=14), prednisolone (n=13), 5-aminosalicylic acid (n=14), I-glutamine (n=14), and short chain fatty acid (n=13) enemas were applied twice daily to the rats for seven days after the induction of colitis. The sham group (n=9) received only saline enemas. Rats were killed at the seventh day and their colonic macroscopic inflammatory scores were determined. Colonic mucosal gamma glutamyl transpeptidase activity and colonic mucosal malondialdehyde levels were measured. The same measurements but no enemas were done in the control group (n=7). RESULTS: There were significant differences in macroscopic inflammatory scores between sham and colitis groups (P<0.001). The macroscopic inflammatory scores of the colitis group were higher than the short chain fatty acid and glutamine groups (P<0.05). Whereas the mucosal gamma glutamyl transpeptidase activity was diminished in prednisolone, 5-aminosalicylic acid, and short chain fatty acid groups when compared with the control group; in the colitis, sham, and glutamine groups the activity of this enzyme did not change. The mucosal malondialdehyde levels were significantly lower in the prednisolone and glutamine groups than in the colitis group. CONCLUSION: Only one of four agents tested, namely, I-glutamine enemas, could decrease the severity of colitis both morphologically and biochemically. Moreover, L-glutamine prevented the colitis-induced oxidant injury in the colonic mucosa. On the other hand, prednisolone and short chain fatty acids seemed to improve only the physiologic changes of colitis.

Hypertonic saline dextran alleviates hepatic injury in hypovolemic rats undergoing porta hepatis occlusion.

To monitor the ischemic and/or reperfusion injury after porta hepatis occlusion (Pringle maneuver) in livers subjected to hypotension, serum alanine amino transferase (ALT), liver malondialdehyde (MDA), and liver glutathione (GSH) levels were measured. MDA is a by-product of oxidant-induced lipid peroxidation, and GSH is an endogenous antioxidant. The effects of lactated Ringers (LR) and hypertonic saline (7.5%)/Dextran (6%; HSD) resuscitation on liver injury, if any, was investigated. Rats in sham (S, n = 8) and five other groups (n = 8) underwent femoral artery and vein catheterization and laparotomy. The hemorrhage and ischemia (HI) group was bled 30% of their blood volume and had their porta hepatis occluded for 30 min. The HI, LR, and HSD groups underwent both hemorrhage and occlusion. Thirty minutes after hemorrhage, the LR and HSD groups received either LR (equivalent to three times the shed blood) or HSD (10 mL/kg) resuscitation over 30 min. Both LR and HSD resuscitation lowered the increased ALT and liver tissue MDA seen in the HI group. ALT was decreased from 348 ± 93 IU/L in the HI group to 200 ± 98 IU/L in the LR and 139 ± 74 IU/L in the HSD groups. Liver tissue MDA was 353 ± 22 nmol/g/tissue in the HI group and LR decreased it to 261 ± 17 nmol/g/tissue, whereas HSD decreased it to 273 ± 20 nmol/g/tissue. The decrease in ALT and the increase in liver GSH were more pronounced with HSD resuscitation (P < 0.05). HSD seems to be more effective than LR in decreasing the liver tissue damage produced by total hepatic inflow occlusion under hypovolemic conditions.

PROSTAGLANDIN SYNTHETASE INHIBITION REDUCES PERITONITIS-INDUCED EARLY LIVER OXIDANT STRESS

This study was undertaken to determine whether or not the prostanoid metabolism contributes to peritonitis-induced early liver oxidant stress. Lipid peroxidation products, malondialdehyde (MDA) and conjugated dienes (CD), were used to monitor oxidant stress. The rats were given a 5-cc intraperitoneal (i.p.) injection of 25% rat feces suspension and then received either i.p. saline (peritonitis group,n=11), vitamin E (n=6), or diclofenac (n=6). The liver and plasma MDA and CD levels were measured after 3h. The plasma and liver MDA and CD levels were significantly higher in the peritonitis group than in the control (n=9). Prostaglandin synthetase inhibitor (diclofenac) kept the liver and plasma MDA and CD at control levels. Antioxidant alpha tacopherol (vitamin E) was thus found not to be effective in reducing these increased MDA and CD levels. Peritonitis-induced early oxidant stress in the liver seems to be mediated by the oxidant-independent activation of the cyclooxygenase pathway.

Oxothiazolidine carboxylate provides protection against hepatocellular injury seen after porta hepatis occlusion (Pringle maneuver) under hypovolemic conditions

The sensitivity of liver to warm ischemia has always been a concern for surgeons. To monitor the ischemia and/or reperfusion injury after the Pringle maneuver (occlusion of porta hepatis) in livers subjected to hemorrhage, blood pressure, blood pH, base deficit (BE), serum alanine aminotransferase (ALT), serum and liver malondialdehyde (MDA), and liver glutathione (GSH) levels were measured. MDA is a by-product of oxidant induced lipid peroxidation, and GSH is an endogenous antioxidant. The effect of lactated Ringer’s (LR) resuscitation with or without the addition of 2-oxothiazolidine-4-carboxylate (OTC), a cysteine prodrug (enhancing glutathione production) on liver injury, if any, were investigated. Rats in the sham group (n = 8) and five other groups (n = 8) underwent femoral artery and vein catheterization and laparotomy. The hemorrhage group was bled 30% of their blood volume and the ischemia group underwent occlusion of the porta hepatis 30 minutes. The hemorrhage-ischemia (HI), LR, and OTC groups underwent both hemorrhage and occlusion. The LR and OTC groups, 30 minutes after hemorrhage, received either LR resuscitation (equivalent to three times the shed blood) or LR resuscitation plus IV OTC (100 mg/kg before clamping and 100 mg/kg after de-clamping). Porta hepatis occlusion in the presence of hypovolemia (HI group) caused an increase in serum ALT, plasma MDA, liver MDA, and base deficit and a decrease in blood pH levels. LR resuscitation lowered only MDA (plasma and liver) and base deficit but did not reduce ALT and increase blood pH. Although liver GSH did not change, OTC kept all parameters at control levels. OTC prevents the deleterious effects of total hepatic inflow occlusion under hypovolemic conditions, but this does not occur through enhancement liver glutathione production. OTC may protect the liver by accelerating hepatic glutathione turnover, but further studies are needed to explain its mechanism of action.