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Innovative Molecular Methodologies and Models in Assessing the Toxicity Potential...
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Innovative Molecular Methodologies and Models in Assessing the Toxicity Potential of Natural Products

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 7733

Special Issue Editors

Dr. Igor Koturbash

E-Mail Website
Guest Editor
1. Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2. Center for Dietary Supplements Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Interests: diet and dietary supplements; molecular toxicology; herb-induced liver injury; hepatotoxicity; dietary modulation of normal and cancerous tissue response to cancer therapy
Dr. Bill J. Gurley

E-Mail Website
Guest Editor
National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA
Interests: pharmacokinetics; natural products; dietary supplements; herb-drug interactions

Special Issue Information

Dear Colleagues,

Natural products have gained widespread acceptance among consumers worldwide. Unlike conventional medications, natural products sold in the form of dietary supplements are not required to undergo pre-market approval testing for safety; thus, the toxicity potential of such products is not realized until after their ingestion by the consuming public. This regulatory shortcoming is especially concerning with regard to unusual and heretofore untested combinations of exotic botanical extracts or purified phytochemicals. Of particular concern are hepato- and cardiotoxicity, as well as herb–herb and herb–drug interactions, which become especially concerning in lieu of the continuously growing number of natural products on the market.

Therefore, the development of novel molecular toxicology approaches and models that can effectively address these deficiencies is urgently required. In these regards, in silico approaches, microphysiological systems that mimic the complexity of human physiology and pathophysiology in an organ-specific context, and specialized animal models are of particular interest.

Dr. Igor Koturbash
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • botanicals
  • phytochemicals
  • natural products
  • dietary supplements
  • toxicity
  • molecular toxicology
  • herb–drug interaction
  • herb–herb interaction
  • models
  • organ-on-chip

Published Papers (2 papers)

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Research

13 pages, 2210 KiB  
Article
Dietary Methionine Deficiency Enhances Genetic Instability in Murine Immune Cells
by Regina L. Binz, Ratan Sadhukhan, Isabelle R. Miousse, Sarita Garg, Igor Koturbash, Daohong Zhou, Martin Hauer-Jensen and Rupak Pathak
Int. J. Mol. Sci. 2021, 22(5), 2378; https://doi.org/10.3390/ijms22052378 - 27 Feb 2021
Cited by 5 | Viewed by 2575
Abstract
Both cell and animal studies have shown that complete or partial deficiency of methionine inhibits tumor growth. Consequently, the potential implementation of this nutritional intervention has recently been of great interest for the treatment of cancer patients. Unfortunately, diet alteration can also affect [...] Read more.
Both cell and animal studies have shown that complete or partial deficiency of methionine inhibits tumor growth. Consequently, the potential implementation of this nutritional intervention has recently been of great interest for the treatment of cancer patients. Unfortunately, diet alteration can also affect healthy immune cells such as monocytes/macrophages and their precursor cells in bone marrow. As around half of cancer patients are treated with radiotherapy, the potential deleterious effect of dietary methionine deficiency on immune cells prior to and/or following irradiation needs to be evaluated. Therefore, we examined whether modulation of methionine content alters genetic stability in the murine RAW 264.7 monocyte/macrophage cell line in vitro by chromosomal analysis after 1-month culture in a methionine-deficient or supplemented medium. We also analyzed chromosomal aberrations in the bone marrow cells of CBA/J mice fed with methionine-deficient or supplemented diet for 2 months. While all RAW 264.7 cells revealed a complex translocation involving three chromosomes, three different clones based on the banding pattern of chromosome 9 were identified. Methionine deficiency altered the ratio of the three clones and increased chromosomal aberrations and DNA damage in RAW 264.7. Methionine deficiency also increased radiation-induced chromosomal aberration and DNA damage in RAW 264.7 cells. Furthermore, mice maintained on a methionine-deficient diet showed more chromosomal aberrations in bone marrow cells than those given methionine-adequate or supplemented diets. These findings suggest that caution is warranted for clinical implementation of methionine-deficient diet concurrent with conventional cancer therapy. Full article
(This article belongs to the Special Issue Innovative Molecular Methodologies and Models in Assessing the Toxicity Potential of Natural Products)
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14 pages, 12612 KiB  
Article
Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration
by Kristy R. Kutanzi, Laura E. Ewing, Charles M. Skinner, Charles M. Quick, Stefanie Kennon-McGill, Mitchell R. McGill, Larry A. Walker, Mahmoud A. ElSohly, Bill J. Gurley and Igor Koturbash
Int. J. Mol. Sci. 2020, 21(20), 7808; https://doi.org/10.3390/ijms21207808 - 21 Oct 2020
Cited by 5 | Viewed by 4470
Abstract
Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions [...] Read more.
Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model. For this purpose, 8-week-old male C57BL6/J mice received MSM-containing water (80 mg/100 mL) ad libitum for 17 days. During the last three days of treatment, mice received three doses of CRCE administered in sesame oil via oral gavage (123 mg/kg/day). Administration of MSM alone did not result in any evidence of liver toxicity and did not induce expression of mouse cytochrome P450 (CYP) enzymes. Administration of CRCE did produce significant (p < 0.05) increases in Cyp1a2, Cyp2b10, Cyp2c29, Cyp3a4, Cyp3a11, Cyp2c65, and Cyp2c66 messenger RNA, however, this effect was not amplified by MSM/CRCE co-treatment. Similarly, no evidence of liver toxicity was observed in MSM/CRCE dosed mice. In conclusion, short-term MSM/CRCE co-administration did not demonstrate any evidence of hepatotoxicity in the mouse model. Full article
(This article belongs to the Special Issue Innovative Molecular Methodologies and Models in Assessing the Toxicity Potential of Natural Products)
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