The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats

Abstract

Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and olfactory bulb) was examined. Twenty pregnant female Wistar rats at gestational day 18 were used. Pregnant rats were divided into four groups: Control, APAP, E + APAP, and APAP + E. The Control group was treated with 0.5 mL p.o. corn oil. The APAP group received 3000 mg/kg p.o. APAP. The E + APAP group received 300 mg/kg p.o. vitamin E one hour before 3000 mg/kg APAP. The APAP + E group received 3000 mg/kg paracetamol one hour before 300 mg/kg p.o. vitamin E. Twenty-four hours after the last treatment administration, rats were euthanized and blood, brain, liver, and kidney samples were collected. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine levels, uric acid (UA), and superoxide dismutase (SOD) levels, as well as the relative mRNA expression of Cyp1a4, Cyp2d6, and Nat2, were determined. Acute APAP treatment upregulated ALT, AST, BUN, and creatinine levels. APAP treatment downregulated UA and SOD levels. APAP treatment upregulated the relative mRNA expression of Cyp1a4 and Cyp2d6, but downregulated Nat2 expression. Vitamin E treatment, either before or after APAP administration, attenuated the toxic effects of APAP. In conclusion, the results showed that an acute toxic APAP dose in late pregnancy can cause oxidative stress and dysregulation in Cyp isoform expression, and that vitamin E treatment attenuates these effects.

Keywords

• APAP
• <i>Cyp1a2</i>
• <i>Cyp2d6</i>
• <i>Nat2</i>
• ALT
• AST