Crambescidin-816 Acts as a Fungicidal with More Potency than Crambescidin-800 and -830, Inducing Cell Cycle Arrest, Increased Cell Size and Apoptosis in Saccharomyces cerevisiae

In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infectionsThe research leading to these results has received funding from the following FEDER cofunded-grants: From Ministerio de Ciencia y Tecnología, Spain: AGL2009-13581-CO2-01, AGL2012-40485-CO2-01. From Xunta de Galicia, Spain: 10PXIB261254 PR. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007-2013) under grant agreement Nos. 211326—CP (CONffIDENCE), 265896 BAMMBO, 265409 µAQUA, and 262649 BEADS, 315285 Ciguatools and 312184 PharmaSea. From the Atlantic Area Programme (Interreg IVB Trans-national): 2009-1/117 PharmatlanticS

Oral Toxicity of Okadaic Acid in Mice: Study of Lethality, Organ Damage, Distribution and Effects on Detoxifying Gene Expression

In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animalsThe research leading to these results has received funding from the following FEDER cofunded-grants: From Ministerio de Ciencia y Tecnología, Spain: AGL2009-13581-CO2-01, AGL2012-40485-CO2-01. From Xunta de Galicia, Spain: 10PXIB261254 PR. From the European Union’s Seventh Framework Programme managed by REA–Research Executive Agency (FP7/2007-2013) under grant agreement Nos. 265896 BAMMBO, 265409 µAQUA, and 262649 BEADS, 315285 Ciguatools and 312184 PharmaSea. From the Atlantic Area Programme (Interreg IVB Trans-national): 2009-1/117 PharmatlanticS