Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: In vivo and in vitro studies

Figure 1 The metabolism of NO in the circulation: the NO produced circulates both as nitrite/nitrate and in complexes as protein and nonprotein S-nitrosothiols. The formation of S-NO adducts, as well as the release of NO from these compounds, is strongly influenced by the bioavailability of glutathione (GSH) and cysteine (CYS) and by the redox status of plasma.

Figure 2 A: Correlation between S-NO and platelet number in each patient. As evident, S-NO levels were significantly directly correlated with platelet number (r = 0.58, P < 0.01). S-NO: S-nitrosothiol; B: Correlation between S-NO and % of platelet aggregation in each patient. As evident, S-NO levels were significantly inversely correlated with percent of platelet aggregation (r = -0.52, P < 0.05).

Figure 3 Percentage aggregation (mean ± SD) obtained in HCV-positive patients and controls, in basal conditions and after incubation with GSNO. Compared with controls % maximal aggregation induced by ADP was significantly increased in CH patients. Moreover, the collagen addition induced a significant increase in % maximal aggregation in the platelets from CH patients. After incubation with GSNO, % maximal aggregation induced by ADP was significantly reduced in both groups, but the reduction was much more evident in the CH patients, while % maximal aggregation induced by ADP was not changed by the addition of GSNO in control group and was significant reduced in CH patients. C: controls; CH: chronic hepatitis; GSNO: nitrosoglutathione. ^aP < 0.05, ^bP < 0.01 vs ADP; ^dP < 0.01 vs collagen; ^cP < 0.05 vs ADP; ^fP < 0.01 vs collagen.

Figure 4 Aggregation curves of a single representative CH patient before and after GSNO. GSNO was able to reduce platelet % maximal aggregation and modified the curve morphology by abolishing the delay in the beginning of the aggregation. GSNO: nitrosoglutathione.