The Effect of S-Nitroso-N-Acetylpenicillamine and S-Nitroso-Captopril Co-Administered with Cysteine on Blood Glucose Concentration in an Animal Model

Abstract

The study sought to test the hypothesis that co-administration of SNAP and cysteine or CapSNO and cysteine in normoglycaemic rats may further reduce glucose tolerance. An oral glucose tolerance was carried out and the plasma nitrite concentrations were measured and taken as the biochemical markers of in vivo NO formation. The results showed blood glucose levels were significantly elevated at fasting (F2) and 2.5 h time intervals of the oral glucose tolerance test on administration of SNAP at 12.5 mg kg^-1 body weight (BW) or CapSNO at 12.5 mg kg^-1 BW compared to captopril (12.5 mg kg^-1 BW, control). Co-administration of SNAP and cysteine (30 mg kg^-1 BW), or CapSNO and cysteine enhanced the postprandial hyperglycemic effect at the 2.0 or 2.5 h time intervals compared with the administration of SNAP or CapSNO only (p<0.05). The increased postprandial blood glucose concentration was associated with a significant elevation of NO produced from CapSNO and SNAP as assessed by plasma nitrite concentration. Co-administration of cysteine and CapSNO caused a significant increase in total nitrite concentration compared with the administration of only CapSNO (52.63±2.69 µM vs 32.36±3.66 µM, p = 0.03). The results suggested that in normoglycaemic rats, NO released from SNAP and CapSNO caused a significant hyperglycaemic effect (p<0.05). This effect was enhanced by cysteine as evidenced by the observed increased total nitrite concentration resulting in exacerbation of the impaired glucose tolerance.