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

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)...

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Main Authors: Alaa M. Hammad, Baraa Shawaqfeh, Suhair Hikmat, Tariq Al-Qirim, Lama Hamadneh, Sameer Al-Kouz, Mariam M. Awad, Frank S. Hall
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/11/4/368
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author Alaa M. Hammad
Baraa Shawaqfeh
Suhair Hikmat
Tariq Al-Qirim
Lama Hamadneh
Sameer Al-Kouz
Mariam M. Awad
Frank S. Hall
author_facet Alaa M. Hammad
Baraa Shawaqfeh
Suhair Hikmat
Tariq Al-Qirim
Lama Hamadneh
Sameer Al-Kouz
Mariam M. Awad
Frank S. Hall
author_sort Alaa M. Hammad
collection DOAJ
description 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 <i>Cyp1a4</i>, <i>Cyp2d6</i>, and <i>Nat2</i>, 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 <i>Cyp1a4</i> and <i>Cyp2d6</i>, but downregulated <i>Nat2</i> 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.
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spelling doaj.art-800c8762efa94316ae318e4ecfcb87032023-11-17T21:37:53ZengMDPI AGToxics2305-63042023-04-0111436810.3390/toxics11040368The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female RatsAlaa M. Hammad0Baraa Shawaqfeh1Suhair Hikmat2Tariq Al-Qirim3Lama Hamadneh4Sameer Al-Kouz5Mariam M. Awad6Frank S. Hall7Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USAParacetamol (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 <i>Cyp1a4</i>, <i>Cyp2d6</i>, and <i>Nat2</i>, 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 <i>Cyp1a4</i> and <i>Cyp2d6</i>, but downregulated <i>Nat2</i> 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.https://www.mdpi.com/2305-6304/11/4/368APAP<i>Cyp1a2</i><i>Cyp2d6</i><i>Nat2</i>ALTAST
spellingShingle Alaa M. Hammad
Baraa Shawaqfeh
Suhair Hikmat
Tariq Al-Qirim
Lama Hamadneh
Sameer Al-Kouz
Mariam M. Awad
Frank S. Hall
The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
Toxics
APAP
<i>Cyp1a2</i>
<i>Cyp2d6</i>
<i>Nat2</i>
ALT
AST
title The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
title_full The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
title_fullStr The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
title_full_unstemmed The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
title_short The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
title_sort role of vitamin e in protecting against oxidative stress inflammation and the neurotoxic effects of acute paracetamol in pregnant female rats
topic APAP
<i>Cyp1a2</i>
<i>Cyp2d6</i>
<i>Nat2</i>
ALT
AST
url https://www.mdpi.com/2305-6304/11/4/368
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