PubMed · 10366277
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R Walker, O R Dearlove, I Aguilera. 1999. Post tonsillectomy pain.. https://doi.org/10.1046/j.1460-9584.1999.00387.x
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The nitric oxide (NO) donor, O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO in the liver and possibly other tissues. V-PYRRO/NO has been shown to be hepatoprotective, but little is known about its effect in the kidney, another organ rich in P450s. Thus, mice were given V-PYRRO/NO (0.4-5.4 mg/ml, 8 microl/h) before and/or after a nephrotoxic dose of acetaminophen (APAP; 600 mg/kg, i.p.) to examine its nephroprotective effects. V-PYRRO/NO administration significantly reduced APAP-induced nephrotoxicity in a dose- and time-dependent manner, as evidenced by mitigation of increased blood urea nitrogen levels and by amelioration of renal pathology, specifically interstitial congestion, proximal tubular cell degeneration and necrosis. The best protection was observed at the highest dose (5.4 mg/ml) and with V-PYRRO/NO pretreatment (4-16 h). Implanting V-PYRRO/NO pumps simultaneously with APAP also attenuated APAP nephrotoxicity. The protection is probably not due to a decreased APAP toxication metabolism, as similar depletion of renal glutathione levels was observed regardless of V-PYRRO/NO treatment. APAP-induced renal lipid peroxidation was reduced by V-PYRRO/NO, as determined by the concentrations of hydroxynonenals and malondialdehyde. In summary, this study demonstrates that the NO donor V-PYRRO/NO is effective in blocking APAP-induced nephrotoxicity in mice. The protection is probably due to multiple mechanisms involving attenuation of APAP-induced congestion and lipid peroxidation in the kidney.
A method for the quantitative determination of acetaminophen by measuring the kinetics of its oxidation by the enzyme tyrosinase in the presence of the nucleophilic agent 3-methyl-2-benzothiazolone hydrazone (Besthorn's hydrazone) is described. The hydrazone traps the o-quinone product of the catalytic activity, 4-acetamido-o-benzoquinone, thus increasing the level of the catecholic intermediate, 3'-hydroxyacetaminophen, in the pathway, as was shown by liquid chromatography. This reduces the time necessary for the steady state to be reached and increases the steady state oxidation rate, reaching activations of 124 times at an initial concentration of 3mM hydrazone. Despite being rapid and simple the method is thorough and provides a linear range of quantification of the drug from 10 nmol/ml to 1.4 micromol/ml. The assay can be performed in continuous or discontinuous form, meaning that it can be used with the immobilized enzyme for the design of specific biosensors.
The effects of some crystallisation conditions on the formation of orthorhombic paracetamol from ethanolic solution are examined when seeding technique is applied under fixed agitation (700 rpm) and harvesting time (30 min). Three equally spaced levels were used for initial concentration, C(I) (30 +/- 4% w/v), for seeding temperature, T(S) (7 +/- 7 degrees C) and for cooling temperature, T(C) (-10 +/- 10 degrees C). The influences on parameters of temperature change in the crystallisation solution were quantitatively determined as were influences on crystal yield (Y%), crystal size and shape, and orthorhombic content of the final crystalline product. Conditions for improvement of Y% under reproducible formation of orthorhombic form were elucidated. It was found that Y% increases remarkably by increasing C(I) but there is a corresponding decrease in the content of orthorhombic form. Increased content of monoclinic form is explained by nucleation under conditions of high C(I) (34% w/v), low seeding temperature (below 7 degrees C) and long seeding time (more than 14.7 min) in addition to transformation of grown orthorhombic seeds. However, reproducible formation of pure orthorhombic form is possible at medium C(I) (30% w/v) and optimal crystal yield (60.9% w/w) corresponds to -20 degrees C T(C) and 0 degrees C seeding temperature. Crystal size is affected by all the crystallisation conditions due to the alteration in the degree of supersaturation, and consequently, in the nucleation and growth processes. Aspect ratio is affected due to the presence of less elongated monoclinic crystals. The fullness ratio increases with the cooling temperature but decreases with the initial concentration, probably because of secondary nucleation on the crystal surfaces or erosion due to initiation of transformation.