Cargando…

Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is a central dietary mutagen, produced when proteinaceous food is heated at very high temperatures potentially causing DNA strand breaks. This study investigates the protective potential of a well-researched flavonoid, myricetin in its bulk and...

Descripción completa

Detalles Bibliográficos
Autores principales: Akhtar, Shabana, Najafzadeh, Mojgan, Isreb, Mohammad, Newton, Lisa, Gopalan, Rajendran C., Anderson, Diana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367907/
https://www.ncbi.nlm.nih.gov/pubmed/32342131
http://dx.doi.org/10.1007/s00204-020-02754-x
_version_ 1783560509607378944
author Akhtar, Shabana
Najafzadeh, Mojgan
Isreb, Mohammad
Newton, Lisa
Gopalan, Rajendran C.
Anderson, Diana
author_facet Akhtar, Shabana
Najafzadeh, Mojgan
Isreb, Mohammad
Newton, Lisa
Gopalan, Rajendran C.
Anderson, Diana
author_sort Akhtar, Shabana
collection PubMed
description 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is a central dietary mutagen, produced when proteinaceous food is heated at very high temperatures potentially causing DNA strand breaks. This study investigates the protective potential of a well-researched flavonoid, myricetin in its bulk and nano-forms against oxidative stress induced ex vivo/in vitro by PhIP in lymphocytes from pre-cancerous monoclonal gammopathy of undetermined significance (MGUS) patients and those from healthy individuals. The results from the Comet assay revealed that in the presence of myricetin bulk (10 µM) and myricetin nano (20 µM), the DNA damage caused by a high dose of PhIP (100 µM) was significantly (P < 0.001) reduced in both groups. However, nano has shown better protection in lymphocytes from pre-cancerous patients. Consistent results were obtained from the micronucleus assay where micronuclei frequency in binucleated cells significantly decreased upon supplementing PhIP with myricetin bulk (P < 0.01) and myricetin nano (P < 0.001), compared to the PhIP treatment alone. To briefly determine the cellular pathways involved in the protective role of myricetin against PhIP, we studied gene expression of P53 and ATR kinase (ATM- and Rad3-related), using the real-time PCR technique.
format Online
Article
Text
id pubmed-7367907
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-73679072020-07-21 Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients Akhtar, Shabana Najafzadeh, Mojgan Isreb, Mohammad Newton, Lisa Gopalan, Rajendran C. Anderson, Diana Arch Toxicol Nanotoxicology 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is a central dietary mutagen, produced when proteinaceous food is heated at very high temperatures potentially causing DNA strand breaks. This study investigates the protective potential of a well-researched flavonoid, myricetin in its bulk and nano-forms against oxidative stress induced ex vivo/in vitro by PhIP in lymphocytes from pre-cancerous monoclonal gammopathy of undetermined significance (MGUS) patients and those from healthy individuals. The results from the Comet assay revealed that in the presence of myricetin bulk (10 µM) and myricetin nano (20 µM), the DNA damage caused by a high dose of PhIP (100 µM) was significantly (P < 0.001) reduced in both groups. However, nano has shown better protection in lymphocytes from pre-cancerous patients. Consistent results were obtained from the micronucleus assay where micronuclei frequency in binucleated cells significantly decreased upon supplementing PhIP with myricetin bulk (P < 0.01) and myricetin nano (P < 0.001), compared to the PhIP treatment alone. To briefly determine the cellular pathways involved in the protective role of myricetin against PhIP, we studied gene expression of P53 and ATR kinase (ATM- and Rad3-related), using the real-time PCR technique. Springer Berlin Heidelberg 2020-04-27 2020 /pmc/articles/PMC7367907/ /pubmed/32342131 http://dx.doi.org/10.1007/s00204-020-02754-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Nanotoxicology
Akhtar, Shabana
Najafzadeh, Mojgan
Isreb, Mohammad
Newton, Lisa
Gopalan, Rajendran C.
Anderson, Diana
Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients
title Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients
title_full Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients
title_fullStr Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients
title_full_unstemmed Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients
title_short Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients
title_sort ex vivo/in vitro protective effect of myricetin bulk and nano-forms on phip-induced dna damage in lymphocytes from healthy individuals and pre-cancerous mgus patients
topic Nanotoxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367907/
https://www.ncbi.nlm.nih.gov/pubmed/32342131
http://dx.doi.org/10.1007/s00204-020-02754-x
work_keys_str_mv AT akhtarshabana exvivoinvitroprotectiveeffectofmyricetinbulkandnanoformsonphipinduceddnadamageinlymphocytesfromhealthyindividualsandprecancerousmguspatients
AT najafzadehmojgan exvivoinvitroprotectiveeffectofmyricetinbulkandnanoformsonphipinduceddnadamageinlymphocytesfromhealthyindividualsandprecancerousmguspatients
AT isrebmohammad exvivoinvitroprotectiveeffectofmyricetinbulkandnanoformsonphipinduceddnadamageinlymphocytesfromhealthyindividualsandprecancerousmguspatients
AT newtonlisa exvivoinvitroprotectiveeffectofmyricetinbulkandnanoformsonphipinduceddnadamageinlymphocytesfromhealthyindividualsandprecancerousmguspatients
AT gopalanrajendranc exvivoinvitroprotectiveeffectofmyricetinbulkandnanoformsonphipinduceddnadamageinlymphocytesfromhealthyindividualsandprecancerousmguspatients
AT andersondiana exvivoinvitroprotectiveeffectofmyricetinbulkandnanoformsonphipinduceddnadamageinlymphocytesfromhealthyindividualsandprecancerousmguspatients