Next Article in Journal
Targeting the Iron-Response Elements of the mRNAs for the Alzheimer’s Amyloid Precursor Protein and Ferritin to Treat Acute Lead and Manganese Neurotoxicity
Next Article in Special Issue
Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer
Previous Article in Journal
Botulinum Neurotoxin-A Injected Intrastriatally into Hemiparkinsonian Rats Improves the Initiation Time for Left and Right Forelimbs in Both Forehand and Backhand Directions
Previous Article in Special Issue
A Dual Role of Heme Oxygenase-1 in Cancer Cells
Article

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway

1
Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
2
Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt
3
Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
4
Department of Biological and Geological Sciences, Faculty of Education, Ain Shams University, Cairo 11341, Egypt
5
Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(4), 993; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040993
Received: 21 December 2018 / Revised: 14 February 2019 / Accepted: 20 February 2019 / Published: 25 February 2019
(This article belongs to the Special Issue Protective and Detrimental Role of Heme Oxygenase-1)
Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway. View Full-Text
Keywords: paracetamol; Myristica fragrans kernels; heme oxygenase 1; liver paracetamol; Myristica fragrans kernels; heme oxygenase 1; liver
Show Figures

Graphical abstract

MDPI and ACS Style

Dkhil, M.A.; Abdel Moneim, A.E.; Hafez, T.A.; Mubaraki, M.A.; Mohamed, W.F.; Thagfan, F.A.; Al-Quraishy, S. Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway. Int. J. Mol. Sci. 2019, 20, 993. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040993

AMA Style

Dkhil MA, Abdel Moneim AE, Hafez TA, Mubaraki MA, Mohamed WF, Thagfan FA, Al-Quraishy S. Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway. International Journal of Molecular Sciences. 2019; 20(4):993. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040993

Chicago/Turabian Style

Dkhil, Mohamed A., Ahmed E. Abdel Moneim, Taghreed A. Hafez, Murad A. Mubaraki, Walid F. Mohamed, Felwa A. Thagfan, and Saleh Al-Quraishy. 2019. "Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway" International Journal of Molecular Sciences 20, no. 4: 993. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040993

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop