Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis

AIM: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP).Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation.METHODS: AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done.RESULTS: Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO.CONCLUSION: NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress.

Potential effects of L-NAME on alcohol-induced oxidative stress

AIM: Nitric oxide (NO) is a highly reactive oxidant synthesized from L-arginine by nitric oxide synthase (NOS). NO may cause injury through the generation of potent radicals. Nwnitro-L-arginine methyl ester (L-NAME) is a non-selective inhibitor of NOS. We aimed to evaluate whether L-NAME treatment had protective effects against oxidative stress in rats intragastrically fed with ethanol during a 4 wk-period.METHODS: Thirty-six male Wistar rats were divided into 3 equal groups: group 1 (control group-isocaloric dextrose was given), group 2 (6 g/kg.d ethanol-induced group) and group 3 (both ethanol 6 g/kg.d and L-NAME 500 mg/L in drinking water-given group). Animals were sacrificed at the end of 4 wk-experimental period, and intracardiac blood and liver tissues were obtained. Biochemical measurements were performed both in plasma and in homogenized liver tissues. Alanine amino transferase (ALT), aspartate amino transferase (AST), malondialdehyde (MDA), NO, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels were measured by spectrophotometry.RESULTS: ALT and AST in group 2 (62 U/L and 128 U/L,respectively) were higher than those in group 1 (24 U/L and 38 U/L) and group 3 (37 U/L and 81 U/L) (P＜0.001 for both).Plasma and tissue levels of MDA in group 2 (4.66 μmol/L and 0.55 nmol/mg protein) were higher than in group 1 (2.65 μmol/L and 0.34 nmol/mg protein) and group 3 (3.43 μmol/L and 0.36 nmol/mg protein) (P＜0.001 for both). Plasma and liver tissue levels of NO in group 2 (54.67 μmol/L and 586.50 nmol/mg protein) were higher than in group 1 (34.67 μmol/L and 435.33 nmol/mg protein)and group 3 (27.50 μmol/L and 412.75 nmol/mg protein )(P＜0.001 for both). Plasma and liver tissue SOD activities in group 2 (15.25 U/mL and 5.38 U/ mg protein,respectively) were lower than in group 1 (20.00 U/mL and 8.13 U/mg protein) and group 3 (19.00 U/mL and 6.93 U/mg protein) (P＜0.001 for both). Plasma and liver tissue CAT activities in group 2 (145 U/mL and 37 U/ mg protein,respectively) were lower than in group 1 (176 U/mL and 73 U/mg protein) and group 3 (167 U/mL and 61 U/mg protein) (P＜0.001 for both). Meanwhile, erythrocytes and liver tissue levels of GSH in group 2 (4.12 mg/g Hb and 5.38 nmol/mg protein, respectively) were lower than in group 1 (5.52 mg/g Hb and 4.49 nmol/mg protein) and group 3 (5.64 mg/g Hb and 4.18 nmol/mg protein) (P＜0.001 for both).CONCLUSION: Our findings show that L-NAME may produce a restorative effect on ethanol-induced liver damage via decreasing oxidative stress and increasing antioxidant status.