Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: in vivo and in vitro studies.
OBJECTIVE
To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).


METHODS
In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO).


RESULTS
In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150000/microL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFalpha, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150000/microL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen.


CONCLUSIONS
The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.
Federico
A
A
Inter-University Research Centre on Foods, Nutrition and Gastrointestinal Tract, Gastroenterology School, 2nd University of Naples, Via Alcide De Gasperi 80, 84018 Scafati, Italy. alessandro.federico@unina2.it
Filippelli
A
A
Falciani
M
M
Tuccillo
C
C
Tiso
A
A
Floreani
A
A
Naccarato
R
R
Rossi
F
F
Del Vecchio Blanco
C
C
Loguercio
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D003545:Cysteine / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D010976:Platelet Count; D010979:Platelet Function Tests; D026422:S-Nitrosoglutathione / Q000378:metabolism; D026403:S-Nitrosothiols / Q000097:blood* / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood / Q000378:metabolism / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000447:Aldehydes; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D026403:S-Nitrosothiols; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D026422:S-Nitrosoglutathione; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D003545:Cysteine