ascorbic-acid has been researched along with procainamide-4-hydroxylamine* in 2 studies
2 other study(ies) available for ascorbic-acid and procainamide-4-hydroxylamine
| Article | Year |
|---|---|
Procainamide hydroxylamine lymphocyte toxicity--I. Evidence for participation by hemoglobin.
A number of lines of evidence suggest that the lupus-like symptoms associated with procainamide therapy may be caused by products of metabolic N-oxidation. In the present study, the perfusion of the isolated rat liver with a hemoglobin-free solution containing procainamide (100 microM) resulted in the rapid appearance of the N-oxidation metabolite procainamide hydroxylamine in the perfusate. Addition of procainamide hydroxylamine in vitro to whole rat blood (1-40 microM) resulted in a concentration-dependent loss of proliferative response among mononuclear cells isolated from the treated blood and cultured with mitogens (phytohemagglutinin, PHA-P: concanavalin A, Con A; and pokeweed mitogen, PWM), as well as a loss of viability. Similar effects on lymphocyte mitogen responsiveness were observed when procainamide hydroxylamine (1-40 microM) was added to rat whole splenic cell populations. Carbon monoxide or ascorbic acid pretreatment inhibited the toxicity of procainamide hydroxylamine to lymphocytes in whole blood, but only carbon monoxide pretreatment inhibited procainamide hydroxylamine-induced methemoglobin formation. These observations are consistent with the participation of hemoglobin in a redox cycle with procainamide hydroxylamine, generating products which are primarily responsible for its cytotoxicity in blood. Topics: Acecainide; Animals; Ascorbic Acid; Carbon Monoxide; Chemical Phenomena; Chemistry; Hemoglobins; In Vitro Techniques; Liver; Lymphocytes; Male; Methemoglobin; Monocytes; Procainamide; Rats; Rats, Inbred Strains; Spleen; Thymidine | 1989 |
Electrochemical determination of N-oxidized procainamide metabolites and functional assessment of effects on murine cells in vitro.
Because of the implication of N-oxidized metabolites of procainamide in the induction of drug-related lupus, we have studied the electrochemical behavior of these metabolites and developed an electrochemical synthesis of nitrosoprocainamide. This synthesis was developed using procainamide hydroxylamine as the starting material which was oxidized to the nitroso species at an applied potential of 700 mV vs Ag/AgCl using a carbon packed bed bulk electrolysis flow cell. Conversion efficiencies of greater than 95% were achieved with this method. Subsequent studies with a chemically diverse series of biocompounds were used to investigate possible reactions between the procainamide hydroxylamine and nitroso species and these selected molecules. Only antioxidants such as cysteine, glutathione and ascorbic acid were found to react with the nitroso compound as determined by electrochemical methods, and this reaction was characterized as primarily a simple redox reaction at physiological pH. Animal studies conducted with murine spleen cells incubated with mitogens and various procainamide compounds demonstrated that the N-oxidized metabolites are the active immunopharmacologic agents. Topics: Acecainide; Animals; Ascorbic Acid; Cell Survival; Cells, Cultured; Chemical Phenomena; Chemistry; Cysteine; DNA; Electrochemistry; Electrolysis; Glutathione; Hydrogen-Ion Concentration; Kinetics; Mice; Oxidation-Reduction; Procainamide; Rats; Spectrophotometry; Spleen | 1988 |