Brij 35 inhibited the CYP2E1-mediated metabolism and P-gp mediated transport of paracetamol in rats and <i>in vitro</i> models: amelioration of paracetamol toxicity

The harmful by-product of paracetamol is known as N-Acetyl-p-benzoquinoneimine, (NAPQI). When paracetamol is given at therapeutic dosages or in excess, it undergoes Phase I metabolism in the liver <i>via</i> Cytochrome P-450 2E1 (CYP2E1), and then it produces NAPQI. Previous studies reported that a nonionic surfactant known as Brij 35 (Polyoxyethylene lauryl ether) has been shown to be an effective inhibitor of CYP2E1 and P-glycoprotein (P-gp). Hence, this <i>in vitro</i> and <i>in vivo</i> investigation set out to assess Brij 35 impact on paracetamol CYP2E1-mediated metabolism. For the <i>in vitro</i> investigation, isolated rat hepatocytes were used. Male Wistar rats were used for <i>in vivo</i> studies. There were 30 rats in total, with six individuals each group distributed among the five groups. The first group animals received 0.5% sodium carboxy methyl cellulose (control group); the second group animals treated with 300 mg/kg of paracetamol; the third group animals treated with Brij 35 (5 mg/kg) along with 300 mg/kg of paracetamol; the fourth group animals treated with 10 mg/kg of Brij 35 along with 300 mg/kg of paracetamol, and the fifth group animals treated with 20 mg/kg of Brij 35 along with 300 mg/kg of paracetamol for consecutive 21 days. The current study found that paracetamol plasma concentrations were much higher and NAPQI plasma concentrations were much lower when Brij 35 was co-administered may be due to inhibition of CYP2E1-mediated metabolism and P-gp-mediated intestinal transport of paracetamol. Brij 35 also reduced the increased hepatic and renal markers with significant hepatoprotective and nephroprotective changes in the histopathological investigation.