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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MDPI AG
2023-04-01
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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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