STUDYING THE MITOCHONDRIAL TOXICITY OF PARACETAMOL AND ITS METABOLITE NAPQI

Introduction. Antipyretic effect of paracetamol has been known since the late 19th century. But the safety profile of this drug started to be analyzed much later, when some toxic effects were identified in using a drug that contained paracetamol, the most widely known of which was drug-induced liver damage. Aim. To study the effects of paracetamol and its toxic metabolite N-acetyl-p-benzoquinone-imine on the viability and mitochondrial membrane potential of astroglial cells in the cerebral cortex of newborn rats. Materials and Methods. Isolated astrocytes from the brains of newborn rats were exposed to 1 mM of paracetamol or 0.15 mM of its toxic metabolite NAPQI for 24 hours, then cell viability (colorimetric test for assessing the metabolic activity of cells, i.e. MTT method) and mitochondrial membrane potential (using TMPE fluorochrome) were identified. Results and Discussion. The paracetamol metabolite NAPQI decreased cell viability from 0.57 ± 0.02 down to 0.4507 ± 0.03 a.u. and mitochondrial membrane potential from 0.19±0.01 down to 0.16±0.003 a.u., the differences are significant compared to the control (p <0.05). Conclusions. The results obtained indicate the toxic effect provided by the paracetamol metabolite NAPQI on astroglial cells in the brains of newborn rats. Keywords: paracetamol, NAPQI, mitochondrial toxicity, astroglial cells.