Next Article in Journal
Chemical and Genetic Diversity of Nodularia spumigena from the Baltic Sea
Previous Article in Journal
New Typical Vector of Neurotoxin β-N-Methylamino-l-Alanine (BMAA) in the Marine Benthic Ecosystem
Article Menu

Export Article

Open AccessArticle
Mar. Drugs 2016, 14(11), 208; doi:10.3390/md14110208

Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A

1
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA
2
Department of Food Contaminant and Toxicology, National Research Center, Cairo 12622, Egypt
3
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
*
Author to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Received: 1 September 2016 / Revised: 15 October 2016 / Accepted: 1 November 2016 / Published: 9 November 2016
View Full-Text   |   Download PDF [7679 KB, uploaded 9 November 2016]   |  

Abstract

Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST treatments effectively counteracted the toxic effects of PA and normalized most biochemical parameters in rats. DHA and AST can be useful food additives to prevent and reverse PA food-induced toxicity. View Full-Text
Keywords: astaxanthin; BK (Maxi-K) channels; docosahexaenoic acid; food mycotoxin; penitrem A; toxicity astaxanthin; BK (Maxi-K) channels; docosahexaenoic acid; food mycotoxin; penitrem A; toxicity
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Goda, A.A.; Naguib, K.M.; Mohamed, M.M.; Amra, H.A.; Nada, S.A.; Abdel-Ghaffar, A.-R.B.; Gissendanner, C.R.; El Sayed, K.A. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A. Mar. Drugs 2016, 14, 208.

Show more citation formats Show less citations formats

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

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top