Fansidar ® (sulfadoxine/pyrimethamine) and Coartem ® (artemether/lumefantrine) are drugs that destroy malarial parasites and also produce free radicals which cause hemolysis of malaria-parasitized erythrocytes. This study investigated the effect of these drugs on the viscoelasticity of erythrocytes of ten healthy female subjects using the BioProfiler. The concentration for each of the two drugs were determined based on the therapeutic dose as normal, half the therapeutic dose as low and double the therapeutic dose as high. For Fansidar ® , the concentrations were 0.15/0.01 mg/ml (low), 0.30/0.02 mg/ml (normal) and 0.60/0.04 mg/ml (high) based on the adult therapeutic dose of 1500/75 mg of sulfadoxine/pyrimethamine in the drug combination. For Coartem ® , the concentrations were 0.03/0.19 mg/ml (low), 0.06/0.38 mg/ml (normal) and 0.12/0.76 mg/ml (high) based on the adult therapeutic dose of 320/1920 mg of artermether/lumefantrine in the drug combination. There was a statistically significant (p < 0.05) decrease in viscosity, elasticity and relaxation time with Coartem ® at normal and high doses. Fansidar ® also showed significant (p < 0.05) reductions in these parameters only in the high dose. This suggests that Coartem ® generated significant free radicals at normal and high doses, with Fansidar ® only in the high dose, resulting in increased hemolysis and ultimately reduced viscoelasticity.
Background
The main biological activities of cannabis are due to the presence of several compounds known as cannabinoids. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the main cannabinoids. Studies have shown that the effects of THC can be modulated by CBD.
Objective
This study aims to look at the effect of different concentrations of THC and CBD separately and in combination, on blood viscosity, elasticity and membrane integrity.
Methods
Blood samples were collected from twenty-four healthy adult non-smokers. Blood viscosity and elasticity were determined using the Vilastic Scientific Bioprofiler for different concentrations (0, 2.5, 25, 50 and 100 ng/ml) of CBD and THC respectively, as well as in extracts with combinations of CBD and THC in 4:1 and 1:1 ratios respectively. Repeated measures analysis of variance (ANOVA) was used to determine the difference between the means of the groups.
Results
Blood viscosity increased significantly with increasing concentrations of both THC and CBD from 25 ng/ml up to 100 ng/ml ranging from 6.45 ± 0.36 mPa·s to 11.60 ± 1.12 mPa·s for THC and ranging from 5.46 ± 0.24 mPa·s to 9.91 ± 1.10 mPa·s for CBD respectively, being more pronounced in the extracts at 21.33 ± 2.17 mPa·s for the 4THC:1CBD extract and 21.76 ± 1.88 mPa·s for the 1THC:1CBD extract. There was no significant increase in elasticity for THC and CBD separately. However, a significant increase in elasticity was observed in the extracts. THC and CBD affected red cell morphology resulting in complete disintegration at the highest concentrations.
Conclusions
THC and CBD increased red blood cell viscosity and elasticity separately and in combination. They also adversely affected membrane integrity.
Cilostazol is a drug used for the treatment of intermittent claudication caused by narrowing of the blood vessels and reduced oxygen supply, characterized by intense pain in the leg when walking. This study was designed to investigate the effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve. A total of eight healthy adult subjects were studied. Blood samples (0.5 mL) from each subject were mixed with 5, 10, and 20 ?L of the 0.5 mg/mL stock solution of cilostazol to give concentrations of 10, 20, and 40 ?g/mL equivalent to adult doses of 50, 100, and 200?mg, respectively. The control sample had no drug added. The oxygen hemoglobin dissociation curve of each sample was plotted and the P50 determined with a Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA). The mean P50 for the control samples was 28.27???0.43?mm Hg. The values of the samples exposed to 10, 20, and 40 ?g/mL cilostozol were 29.63???0.66, 30.15???0.77, and 31.66???0.62?mm Hg, respectively. There was a statistically significant difference (p?0.01) between the control and samples exposed to 40 ?g/mL cilostazol. This study suggests that cilostazol caused an increase in the release of oxygen from hemoglobin as shown in the P50 values. This effect was significant at the highest concentration of 40 ?g/mL.
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