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Neurotoxicity of Penicillium Crustosum Secondary Metabolites: Tremorgenic Activity of Orally Administered Penitrem A and Thomitrem A and E in Mice

Neurotoxicity of Penicillium Crustosum Secondary Metabolites: Tremorgenic Activity of Orally Administered Penitrem A and Thomitrem A and E in Mice

Angel Moldes-Anaya, Thomas Rundberget, Christiane K Fæste, Gunnar S Eriksen, Aksel Bernhoft

Toxicon. 2012 Dec 15;60(8):1428-35.

PMID: 23085423

Abstract:

Several cases of neurological disease in dogs after poisoning by food- and feed-borne Penicillium toxins in Norway during the last years have uncovered a lack of knowledge regarding the toxicity and mechanism of action of neuroactive mycotoxins. In the present study, the lowest tremor-inducing dose after single oral administration of penitrem A to mice was 0.50 mg/kg bw. The estimated half maximal effective dose (ED(50)) in respect to the visual tremor scale was 2.74 mg/kg bw. Mice receiving the maximum penitrem A dose (8 mg/kg bw) suffered severe spontaneous tremors and even convulsions. Thomitrem A and E are penitrem analogues lacking the C-16-C-18 ether linkage and possessing an olefin at C-18-C-19. Compared with penitrem A, the lowest tremor-inducing dose of thomitrem A was 16-times higher (8 mg/kg bw) and thomitrem E was found to be non-tremorgenic at the highest dose tested (16 mg/kg bw). During a recovery phase of two weeks post administration animals appeared restored and no changes in feeding and other biological processes were observed. An initial dose-related weight reduction was observed 2 days after penitrem A administration. Penitrem A was absorbed and distributed to gastrointestinal tract, liver, kidneys and brain in the mice. Elimination of penitrem A appeared to be mainly hepatic and the highest concentration levels were found 1 h post administration for all investigated organs. The relationship between liver and gastrointestinal tract concentration levels showed time-dependent linear correlation and a doubling within 1.5 h.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP12627359	Penitrem A		12627-35-9	Price

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