5497
Amira Abdel Kareem Mohammed Goda
Biochemical Studies On The Effect Of Astaxanthin And Docosahexaenoic Acid On The Neurotoxicity Caused By Occurrence Of Penitrem In Foods
Penitrem, Astaxanthin, Docosahexaenoic acid, rats, Caenorhbitidis elegans, Schwann cells CRL-2765, neurotransmitters, In- silico.
Penitrem A is a food mycotoxin produced by numerous Penicillium species. Penitrem A is a strong tremorgenic through selective antagonism of BK channels. Astaxanthin is a marine natural xanthophyll carotenoid with documented antioxidant interest. In contrast to other common antioxidants. Astaxanthin can cross blood brain barriers, inducing neuroprotective effects. Docosahexaenoic acid is polyunsaturated ω-3 fatty acid certainly occurring in fish and algae. Docosahexaenoic acid is crucial for normal neurological and cellular development. This study evaluated the protective activity of Astaxanthin and Docosahexaenoic against Penitrem A toxicity using Schwann cells CRL-2765 as an In- vitro model and two In- vivo models Sprague Dawely rats and Caenorhbitidis elegans. Penitrem A inhibited the viability of Schwann cells with an IC50 of 22.6 µM. Treatments with 10-100 µM of Docosahexaenoic acid significantly reversed the Penitrem A toxicity at its IC50 dose and improved the survival of Schwann cells to 70.5% and 98.8%, respectively. Treatment with Astaxanthin 10 µM and 20 µM increased the survival percent to 61.7% and 70.5%, respectively. BK channel inhibition in the nematode Caenorhbitidis elegans is related to abnormal reversal locomotion. Docosahexaenoic acid and Astaxanthin counteracted the In- vivo Penitrem A BK channel antagonistic activity in the Caenorhbitidis elegans. Rats fed on Penitrem A-contaminated diet showed high levels of glutamate, aspartate, and Gamma amino butyric acid neurotransmitters, with observed necrosis or complete absence of Purkinjie neurons. Dopamine, serotonin and Norepinephrine levels were abnormal. Nitric oxide, Malondialdehyde levels significantly increased, while Total antioxidant capacity level significantly decreased in serum and brain homogenate in Penitrem A treated rats. Docosahexaenoic and Astaxanthin remedies effectively reversed Penitrem A neurotoxic effects and normalized most of the studied biochemical parameters. Docosahexaenoic and Astaxanthin may be useful food additives to prevent and reverse Penitrem A food-induced toxicity. In- silico studies were correlated to understand the mode of action of Penitrem analogues. Penitrem A showed the best binding fitting at multiple BK channel crystal structure targeting with the Ca2+ - sensing aspartic acid moieties at the calcium bowel and calcium- binding site.
2018
Ph.d
Ain Shams
Science