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Mar. Drugs 2016, 14(11), 208;

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

Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA
Department of Food Contaminant and Toxicology, National Research Center, Cairo 12622, Egypt
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
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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

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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.

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