IN-VITRO EFFECTS OF PARACETAMOL ON RHEOLOGICAL PROPERTIES OF ERYTHROCYTES AND ITS ANTIOXIDANT PROPERTIES Y.Y. Bilto

Human erythrocytes were pre-incubated in vitro with paracetamol and then erythrocyte’s rheological properties of deformability, osmotic fragility and aggregation were evaluated after being compromised by various means. Paracetamol (1, 2, 4mg/ml) significantly prevented the loss of deformability through 5m diameter pores of erythrocytes dehydrated with hypertonic buffer or with calcium ionophore A23187 at 4 mg/ml. When the potassium ionophore valinomycin was used to induce cell dehydration, paracetamol (4mg/ml) also prevented partially the loss of deformability. Paracetamol (4mg/ml) also decreased significantly erythrocyte osmotic fragility induced by hypotonic saline, and prevented significantly the aggregation of erythrocytes induced by dextran 70. The antioxidant properties of paracetamol was studied by chemical assays and found to be as follows: total antioxidant capacity (88.9 μg AAE/mg), reducing power (A 0 at 700 nm= 1.0 compared to 3.0 for Vit. C), DPPH scavenging activity (IC50= 62.5 μg/ml compared to 5.8 for Vit. C), OH· scavenging activity (IC50= 40.2 μg/ml compared to <10 for catecholamin), iron chelating (IC50= 144.6 μg/ml compared to 17.3 for EDTA) and Paracetamol at 1, 2, 4, 5 mg/ml also prevented significantly lipid peroxidation in a concentration dependent manner of human erythrocytes incubated with H2O2. The observed rheological and anti-lipid-peroxidant effects of paracetamol could be explained by its antioxidant activity, thus protecting membrane integrity and deformability. The results suggest that paracetamol could have a rheologically useful role on erythrocytes, preventing dehydration, aggregation and lipid-peroxidation, that may contribute positively to its analgesic and antipyretic effects. INTRODUCTION: Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug, which in overdose can lead to severe liver and renal damage 1, 2, 3, 4 . Paracetamol is metabolized primarily by conjugation with glucuronic acid and sulfate in the liver. QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.7(2).579-86 Article can be accessed online on: www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.7 (2).579-86 Less than 5% of the given dose is metabolized by hepatic cytochrome P-450 to produce a highly reactive toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified in the hepatocytes by the glutathione system 1, 2, 3, 4 . Once glutathione reserves are depleted, such as in overdose, multiple perturbations ensue that ultimately lead to cell damage. In addition to cellular damage inflicted by NAPQI metabolite, paracetamol itself may directly contribute to toxicity. Paracetamol (even in the absence of cytochrome P450 conversion to NAPQI