Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat

The objective of the present study was to explore the regulatory mechanisms of free radicals during streptozotocin (STZ)-induced pancreatic damage, wh ich may involve nitric oxide (NO) production as a modulator of cellular oxi dative stress. Removal of oxygen species by incubating pancreatic tissues i n the presence of polyethylene glycol-conjugated superoxide dismutase (PEG- SOD) (1 U/ml) produced a decrease in nitrite levels (42%) and NO synthase ( NOS) activity (50%) in diabetic but not in control samples. When NO product ion was blocked by N-G-monomethyl-L-arginine (L-NMMA) (600 muM), SOD activi ty increased (15.21 +/- 1.23 vs 24.40 +/- 2.01 U/mg dry weight). The increa se was abolished when the NO donor, spermine nonoate, was added to the incu bating medium (13.2 +/- 1.32). Lipid peroxidation was lower in diabetic tis sues when PEG-SOD was added (0.40 +/- 0.02 vs 0.20 +/- 0.03 nmol/mg protein ), and when L-NMMA blocked NOS activity in the incubating medium (0.28 +/- 0.05); spermine nonoate (100 muM) abolished the decrease in lipoperoxide le vel (0.70 +/- 0.02). We conclude that removal of oxygen species produces a decrease in pancreatic NO and NOS levels in STZ-treated rats. Moreover, inh ibition of NOS activity produces an increase in SOD activity and a decrease in lipoperoxidation in diabetic pancreatic tissues. Oxidative stress and N O pathway are related and seem to modulate each other in acute STZ-induced diabetic pancreas in the rat.