Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A.
Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marinePenicilliumspecies. 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 wormCaenorhbitidis elegansand Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50of 22.6 μM. Dose-dependent treatments with 10-100 μM DHA significantly reversed the PA toxicity at its IC50dose, 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 IC50dose and raised these cells' survival to 61.7%-70.5%. BK channel inhibition in the nematodeC. elegansis associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in theC. elegansmodel. 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.
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA. amori65@yahoo.com.|Department of Food Contaminant and Toxicology, National Research Center, Cairo 12622, Egypt. amori65@yahoo.com.
Amira A
AA
Goda
Department of Food Contaminant and Toxicology, National Research Center, Cairo 12622, Egypt. naguib_kh@hotmail.com.
Khayria M
KM
Naguib
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt. mutation6119@yahoo.com.
Magdy M
MM
Mohamed
Department of Food Contaminant and Toxicology, National Research Center, Cairo 12622, Egypt. hassanamra2010@yahoo.com.
Hassan A
HA
Amra
Department of Food Contaminant and Toxicology, National Research Center, Cairo 12622, Egypt. somaianada@yahoo.com.
Somaia A
SA
Nada
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt. abdo@abdoscience.com.
Abdel-Rahman B
AB
Abdel-Ghaffar
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA. gissendanner@ulm.edu.
Chris R
CR
Gissendanner
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA. elsayed@ulm.edu.
Khalid A
KA
El Sayed
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D009183:Mycotoxins / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
D000975:Antioxidants; D001688:Biological Products; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009183:Mycotoxins; D018696:Neuroprotective Agents; D024341:Xanthophylls; D004281:Docosahexaenoic Acids; C003626:tremortin; C005948:astaxanthine
BK (Maxi-K) channels; astaxanthin; docosahexaenoic acid; food mycotoxin; penitrem A; toxicity