Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats

<i>Background and objectives:</i> Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular...

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Main Authors: Anmar M. Abdulrazzaq, Mujtaba Badr, Omar Gammoh, Asad A. Abu Khalil, Bayan Y. Ghanim, Tawfiq M. Alhussainy, Nidal A. Qinna
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1010-660X/55/5/181
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author Anmar M. Abdulrazzaq
Mujtaba Badr
Omar Gammoh
Asad A. Abu Khalil
Bayan Y. Ghanim
Tawfiq M. Alhussainy
Nidal A. Qinna
author_facet Anmar M. Abdulrazzaq
Mujtaba Badr
Omar Gammoh
Asad A. Abu Khalil
Bayan Y. Ghanim
Tawfiq M. Alhussainy
Nidal A. Qinna
author_sort Anmar M. Abdulrazzaq
collection DOAJ
description <i>Background and objectives:</i> Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. <i>Materials and Methods:</i> Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. <i>Results:</i> Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. <i>Conclusions:</i> The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.
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spelling doaj.art-bf6e1de7a6584eb79401df0553ae30702023-09-02T00:42:40ZengMDPI AGMedicina1010-660X2019-05-0155518110.3390/medicina55050181medicina55050181Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in RatsAnmar M. Abdulrazzaq0Mujtaba Badr1Omar Gammoh2Asad A. Abu Khalil3Bayan Y. Ghanim4Tawfiq M. Alhussainy5Nidal A. Qinna6Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, JordanUniversity of Petra Pharmaceutical Center (UPPC), University of Petra, P.O. Box 961343, Amman 11196, JordanDepartment of Pharmacy, Faculty of Health Sciences, American University of Madaba, P.O. Box 2882, Madaba 11821, JordanUniversity of Petra Pharmaceutical Center (UPPC), University of Petra, P.O. Box 961343, Amman 11196, JordanUniversity of Petra Pharmaceutical Center (UPPC), University of Petra, P.O. Box 961343, Amman 11196, JordanDepartment of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, JordanDepartment of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan<i>Background and objectives:</i> Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. <i>Materials and Methods:</i> Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. <i>Results:</i> Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. <i>Conclusions:</i> The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.https://www.mdpi.com/1010-660X/55/5/181acetaminophenascorbic acidsilymarinhepatoprotectionhepatotoxicityhepatocytesoxidative stress
spellingShingle Anmar M. Abdulrazzaq
Mujtaba Badr
Omar Gammoh
Asad A. Abu Khalil
Bayan Y. Ghanim
Tawfiq M. Alhussainy
Nidal A. Qinna
Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
Medicina
acetaminophen
ascorbic acid
silymarin
hepatoprotection
hepatotoxicity
hepatocytes
oxidative stress
title Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
title_full Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
title_fullStr Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
title_full_unstemmed Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
title_short Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
title_sort hepatoprotective actions of ascorbic acid alpha lipoic acid and silymarin or their combination against acetaminophen induced hepatotoxicity in rats
topic acetaminophen
ascorbic acid
silymarin
hepatoprotection
hepatotoxicity
hepatocytes
oxidative stress
url https://www.mdpi.com/1010-660X/55/5/181
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