Health Effects of Penitrem A – Oxidative Stress

 

 

This page lists medical journal articles discussing the association between oxidative stress issues and the mycotoxin known as penitrem A.

The Health Effects of Penitrem A page of the Paradigm Change site provides further information on the effects of this mycotoxin.

 

Berntsen HF, Bogen IL, Wigestrand MB, Fonnum F, Walaas SI, Moldes-Anaya A. The fungal neurotoxin penitrem A induces the production of reactive oxygen species in human neutrophils at submicromolar concentrations. Toxicology. 2017 Dec 1;392:64-70. PMID: 29037868

Penitrem A significantly increased the production of ROS in human neutrophils at concentrations as low as 0.25μM (40% increase over basal levels). ROS formation was significantly inhibited by the antioxidant vitamin E (50μM), the intracellular Ca+2 chelator BAPTA-AM (5μM), the mitogen activated protein kinase kinase (MEK) 1/2 and 5 inhibitor U0126 (1 and 10μM), the p38 mitogen activated protein kinase (MAPK) inhibitor SB203580 (1μM), the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 (10μM), and the calcineurin inhibitors FK-506 and cyclosporine A (1.5 and 0.5μM, respectively). These findings suggest that penitrem A is able to induce an increase in ROS production in neutrophils via the activation of several MAPK-signalling pathways.

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Goda AA, Naguib KM, Mohamed MM, Amra HA, Nada SA, Abdel-Ghaffar AB, Gissendanner CR, El Sayed KA. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A. Mar Drugs. 2016 Nov 9;14(11). pii: E208. PMID: 27834847

This study evaluated the protective activity of Astaxanthin (AST) and docosahexaenoic acid (DHA) against Penitrem A (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.

 

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