The antifibrotic and fibrolytic properties of date fruit extract via modulation of genotoxicity, tissue-inhibitor of metalloproteinases and nuclear factor- kappa B pathway in a rat model of hepatotoxicity

Hala Attia, Nouf Al-Rasheed, Raeesa Mohamad, Nawal Al-Rasheed, Maha Al-Amin

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6 Citations (Scopus)

Abstract

Background: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-ΚB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases -1 and -2. Methods: Rats were divided into the following groups: normal control, model control (CCl4 only), CCl4 + DFE, CCl4 + DPE and CCl4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl4 (0.4 ml/kg) 3� a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test. Results: Both DFE and DPE significantly attenuated CCl4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-ΚB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases -1 and -2 suggesting their fibrolytic activity. Conclusion: Our data suggest that DFE or DPE can prevent liver fibrosis by suppressing genotoxicity and nuclear factor-ΚB inflammatory pathway and by promoting collagen degradation.

Original languageEnglish
Article number414
JournalBMC Complementary and Alternative Medicine
Volume16
Issue number1
DOIs
Publication statusPublished - 24 Oct 2016

Fingerprint

Tissue Inhibitor of Metalloproteinases
NF-kappa B
Liver
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Fibrosis
Collagen
Coffee
DNA Damage
Heme Oxygenase-1
Matrix Metalloproteinase Inhibitors
Carbon Tetrachloride
Matrix Metalloproteinase 9
Liver Failure
Liver Cirrhosis
Catalase
Smooth Muscle
Phoeniceae
Liver Diseases
Actins

Keywords

  • 8-hydroxy deoxyguanosine
  • Cycloxygenase-2
  • Date Fruits
  • Liver fibrosis
  • Matrix metalloproteinase
  • Nuclear factor-kappa B

Cite this

@article{9368a750f6064e9f9d0ba0c697fcd5ed,
title = "The antifibrotic and fibrolytic properties of date fruit extract via modulation of genotoxicity, tissue-inhibitor of metalloproteinases and nuclear factor- kappa B pathway in a rat model of hepatotoxicity",
abstract = "Background: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-ΚB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases -1 and -2. Methods: Rats were divided into the following groups: normal control, model control (CCl4 only), CCl4 + DFE, CCl4 + DPE and CCl4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl4 (0.4 ml/kg) 3{\"i}¿½ a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test. Results: Both DFE and DPE significantly attenuated CCl4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-ΚB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases -1 and -2 suggesting their fibrolytic activity. Conclusion: Our data suggest that DFE or DPE can prevent liver fibrosis by suppressing genotoxicity and nuclear factor-ΚB inflammatory pathway and by promoting collagen degradation.",
keywords = "8-hydroxy deoxyguanosine, Cycloxygenase-2, Date Fruits, Liver fibrosis, Matrix metalloproteinase, Nuclear factor-kappa B",
author = "Hala Attia and Nouf Al-Rasheed and Raeesa Mohamad and Nawal Al-Rasheed and Maha Al-Amin",
year = "2016",
month = "10",
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doi = "10.1186/s12906-016-1388-2",
language = "English",
volume = "16",
journal = "BMC Complementary and Alternative Medicine",
issn = "1472-6882",
publisher = "BioMed Central Ltd.",
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}

The antifibrotic and fibrolytic properties of date fruit extract via modulation of genotoxicity, tissue-inhibitor of metalloproteinases and nuclear factor- kappa B pathway in a rat model of hepatotoxicity. / Attia, Hala; Al-Rasheed, Nouf; Mohamad, Raeesa; Al-Rasheed, Nawal; Al-Amin, Maha.

In: BMC Complementary and Alternative Medicine, Vol. 16, No. 1, 414, 24.10.2016.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The antifibrotic and fibrolytic properties of date fruit extract via modulation of genotoxicity, tissue-inhibitor of metalloproteinases and nuclear factor- kappa B pathway in a rat model of hepatotoxicity

AU - Attia, Hala

AU - Al-Rasheed, Nouf

AU - Mohamad, Raeesa

AU - Al-Rasheed, Nawal

AU - Al-Amin, Maha

PY - 2016/10/24

Y1 - 2016/10/24

N2 - Background: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-ΚB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases -1 and -2. Methods: Rats were divided into the following groups: normal control, model control (CCl4 only), CCl4 + DFE, CCl4 + DPE and CCl4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl4 (0.4 ml/kg) 3� a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test. Results: Both DFE and DPE significantly attenuated CCl4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-ΚB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases -1 and -2 suggesting their fibrolytic activity. Conclusion: Our data suggest that DFE or DPE can prevent liver fibrosis by suppressing genotoxicity and nuclear factor-ΚB inflammatory pathway and by promoting collagen degradation.

AB - Background: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-ΚB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases -1 and -2. Methods: Rats were divided into the following groups: normal control, model control (CCl4 only), CCl4 + DFE, CCl4 + DPE and CCl4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl4 (0.4 ml/kg) 3� a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test. Results: Both DFE and DPE significantly attenuated CCl4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-ΚB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases -1 and -2 suggesting their fibrolytic activity. Conclusion: Our data suggest that DFE or DPE can prevent liver fibrosis by suppressing genotoxicity and nuclear factor-ΚB inflammatory pathway and by promoting collagen degradation.

KW - 8-hydroxy deoxyguanosine

KW - Cycloxygenase-2

KW - Date Fruits

KW - Liver fibrosis

KW - Matrix metalloproteinase

KW - Nuclear factor-kappa B

UR - http://www.scopus.com/inward/record.url?scp=84992426947&partnerID=8YFLogxK

U2 - 10.1186/s12906-016-1388-2

DO - 10.1186/s12906-016-1388-2

M3 - Article

VL - 16

JO - BMC Complementary and Alternative Medicine

JF - BMC Complementary and Alternative Medicine

SN - 1472-6882

IS - 1

M1 - 414

ER -