Neurotoxic Effect of Paracetamol on Female Rats: Role of Antioxidant Treatment and Prevention

Abstract

Paracetamol (Acetaminophen) is the most common nonprescription analgesic and antipyretic drug used. It can be found in different pharmaceutical dosage forms such as syrup, capsule, suppositories and intravenous (I.V) infusion solution. The intake frequency and the dose of paracetamol usually varied during pregnancy with a tendency toward higher doses in the last trimester. The effect of Paracetamol overdose was extensively studied on hepatocyte and nephrocyte of laboratory animals. The aim of this study is to focus on the effect of paracetamol overdose on Neurotoxicity (within Hippocampus, Cerebellum, and Olfactory Bulbs) of Paracetamol in the last trimester of pregnant rats. And this will be done through studying oxidative stress markers, the biochemical and antioxidant tests that indicate the presence of Hepatotoxicity and Nephrotoxicity, along with the protective effect of Vitamin E as antioxidant in pre‐ and post‐single toxic dose administration. Twenty female pregnant Wistar rats (average weight 200 gm ± 10) at gestational day 18 (GD18) were used. The pregnant rats were divided into four groups; the first (control) group received a 0.5 ml p.o of corn oil. The second group (paracetamol) group received a 3000 mg/kg p.o paracetamol dissolved in corn oil. The third (E + paracetamol) group received a 3000 mg/kg paracetamol one hour after 300 mg/kg p.o vitamin E. The fourth (paracetamol + E) group received a 3000 mg/kg paracetamol one hour before 300 mg/kg p.o vitamin E dissolved in corn oil. Twenty‐four hours After Paracetamol administration the rats were anesthetized and the brain, the liver, the kidney, and the blood were collected. Various biochemical tests were performed to show the effect of paracetamol overdose on liver including Alanine aminotransferase (ALT), Aspartate aminotransferase (AST). Additionally, the effect of paracetamol on Blood urea nitrogen (BUN) and Creatinine levels were determined to detect nephrotoxicity, and the results showed significant elevation within the paracetamol treated group and levels were restored to the normal levels with vitamin E treated groups. Uric acid (UA) and superoxide dismutase (SOD) were used to detect the oxidative stress within the Liver, the Kidney, the Hippocampus, the Cerebellum, and the Olfactory Bulbs.Support or Funding InformationThis research is supported form Al‐Zaytoonah University of Jordan