The effect of exogenous L-arginine on the arginase, paraoxonase, nitric oxide and antioxidant enzyme level in streptozotocin induced diabetic rats

ABSTRACTTHE EFFECT OF EXOGENOUS L-ARGININE ON THE ARGINASE,PARAOXONASE, NITRIC OXIDE AND ANTIOXIDANT ENZYME LEVELIN STREPTOZOTOCIN INDUCED DIABETIC RATSBulent TASDEMIRDiabetes mellitus is a group of metabolic diseases characterized byhyperglycemia resulting from defects in insulin secretion, insulin action, orboth. Oxidative stress has an important role on diabetes and pathogenesisof the further complications of diabetes. The levels of induced free-radicalsand decline of antioxidant defense mechanisms can lead to damage ofenzymes and cell organelles, increased lipid peroxidation anddevelopment of insulin resistance.In the present study, it was aimed to investigate the effect of L-arginine given intrapertoneally on the arginase, paraoxonase (PON1),nitric oxide, malondialdehyde (MDA) and some antioxidant enzyme levelsin streptozotocin-induced diabetic rats.Twelve weeks-old wistar albino male rats were used for the study.The rats were separated in to four groups as following: control, diabetic,diabetic+L-arginin and L-arginine. The control group was induced by theinjection of only fosfate-citrat buffer intraperitonelly (0.5 ml/ rat) in rats. Thediabet group was caused by the injection of streptozotocin intraperitoneally(55 mg/kg body weight, in fosfate-citrat buffer). Diabet+L-arginin and L-arginin groups were given by the injection of 10 mM L-arginine (0.5ml/each rat) intraperitoneally.Plasma (5.72±0.31 nmol/ml), liver (1.15±0.24 nmol/g protein) andkidney (1.51±0.31 nmol/g protein) MDA levels were significantly increasedin the diabetic group compared to the control group (p<0.05). Plasma(3.9±0.66) and liver (0.48±0.13) MDA levels of diabetic +L-arginin groupwere significantly decreased when compared to the diabetic group(p<0.05).Erythrocyte (14.54±3.47 U/g Hb), liver (1.48±0.36 U/g protein) andkidney (1.52±0.22 U/g protein) GSH-Px activities reduced significantly inthe diabetic group in comparison to the control group (19.41±3.55 ,3.33±0.25 , 3.44±0.29, respectively ) , on the other hand a significant toimprovement was observed in the diabetic +L-arginin group in comparisonto the diabetic group.Erythrocyte (40.72±9.82 k/g Hb), liver (181±10.71 k/g protein) andkidney (7.64±0.57 k/g protein) catalase activities reduced in the diabeticgroup in comparison to the control group (59.41±13.95 , 209.16±11.93,14.83±2.48, respectively), but a significant increase was observed in thediabetic +L-arginin group in comparison to the diabetic group (p<0.05).The activity of arginase enzyme in liver (266.9±18.45 U/mg protein)and kidney (8.86±1.01 U/mg protein) of diabetic group was significantlyhigher than the control group (159.61±11.97, 7.81±0.82, respectively). Nosignificant difference was observed between the control group anddiabetic +L-arginin group (165.6±14.56, 8.73±1.9 respectively) in the liverand kidney arginase enzyme activity levels.Plasma (34.66±3.75 µmol/L) and kidney (28.74±2.01 µmol/L) nitricoxide levels reduced significantly in the diabetic group in comparison tothe control group (47.2±7.77, 33.14±2.84), but the liver tissue nitric oxidelevels (23.91±1.69) were significantly increased in the diabetic group(25.63±2.0) in comparison to the control group (p<0.05).The activity of SOD enzyme of diabetic group (320.09±45.03 U/gHb) reduced in comparison to the control (396.73±66.95 U/g Hb) group(p<0.05).The levels of plasma PON 1 activities reduced in the diabetic group(57.22±13.17 U/L) in comparison to the control group (72.47±9.55 U/L).L- arginin is also metabolized to L-ornithine, which can beprocessed to polyamines and proline. As polyamines are importantmediators of cell growth and L-proline is a substrate for collagensynthesis, it is thought that both pathways have an important role onpancreatic repair processes.In conclusion, it was observed that L-arginine has a regulatoryeffect on the antioxidant system in induced diabetic rats. In addition to this,it was also observed that L-arginine may be useful in the prevention orreduction of oxidative stress depending on diabetes.Key words: Diabetes mellitus, L- arginine, antioxidant enzymes, rat,arginase, MDA, NO.