Disease relevance of Secalonic acid D

• Enhancement of influenza virus infections by secalonic acid D [1].
• Relevance of the palatal protein kinase A pathway to the pathogenesis of cleft palate by secalonic acid D in mice [2].
• The mechanism of the antitumor activity of 5,5'-bis(2'-tetrahydropyranyl) secalonic acid D (PSA) was examined in Balb/c mice bearing Meth-A fibrosarcoma [3].
• Toxicity of Secalonic acid D [4].
• Exposure to a single lethal dose iv (25 mg/kg or more) of secalonic acid D caused limited hepatic portal necrosis but no peritonitis or other associated local effects observed in CD-1 male mice after ip exposure [4].

High impact information on Secalonic acid D

• Secalonic acid D uncoupled the oxidative phosphorylation of mitochondria and caused a mild inhibition of state 3 respiration [5].
• Inhibition by secalonic acid D of oxidative phosphorylation and Ca2+-induced swelling in mitochondria isolated from rat livers [5].
• The in vitro biological activity of secalonic acid D, a mycotoxin from Aspergillus ochraceus, was studied to assess its cytotoxicity for isolated rat liver mitochondria [5].
• Secalonic acid D (SAD), a mycotoxin causing cleft palate (CP), induces phosphorylation of palatal CREB in vivo [6].
• Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D [7].

Biological context of Secalonic acid D

• Secalonic acid D inhibited the three isozymes similarly (IC50 of 5 to 6.2 microM by direct extrapolation and 2.7 to 4 microM by logarithmic regression) [8].
• Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate [6].
• Craniofacial tissues including the secondary palate are vulnerable to disruption of cell cycle progression and proliferation by many chemicals including mycotoxin, secalonic acid D (SAD), glucocorticoids, retinoic acid and 2,3,7,8-tetrachlorodibenzodioxin [9].
• Behavioral and developmental effects in suckling mice following maternal exposure to the mycotoxin secalonic acid D [10].
• This review summarizes the available data on the essential role of this pathway in embryonic development as well as the functionality, ontogeny and consequences of genetic and chemical disruption of this pathway in the developing orofacial structures, especially the secondary palate as influenced by the mycotoxin, secalonic acid D [11].

Anatomical context of Secalonic acid D

• Incidence of cleft palate (CP) in full-term mouse fetuses was evaluated following administration of 25 mg/kg of the mycotoxin, secalonic acid D (SAD), to groups of female mice on each of Days 10, 11, 12, 13, 14, or 15 of pregnancy [12].
• A crucial role of the site of administration in the sensitivity of the alternative system using chick embryo for testing embryotoxicity was demonstrated by morphological evaluation of the effects of T-2 toxin and secalonic acid D, and by incorporation of [14C]sodium acetate radioactivity [13].
• Secalonic acid D, however, failed to induce dominant lethal mutations but produced a slight but statistically significant increase in the number of micronucleated polychromatic erythrocytes in mouse bone marrow at maximally tolerated doses [14].
• Two rodent mutagenicity tests, the dominant lethal test designed to evaluate male germ cell mutations and the micronucleus test designed to evaluate somatic cell mutations, were conducted in mice to assess the carcinogenic potential of secalonic acid D [14].

Gene context of Secalonic acid D

• Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E [15].
• Secalonic acid D also inhibits Ca2+-calmodulin-dependent myosin light chain kinase (MLCK) and plant Ca2+-dependent protein kinase (CDPK) [16].
• The results indicated that secalonic acid D is embryocidal and teratogenic as well as fetotoxic when given to female CD1 mice during pregnancy [17].
• Inhibition of adenylate cyclase in perfusion mouse palate by secalonic acid D [18].
• Death resulting from cardiac and/or pulmonary insufficiency was suggested by atelectasis, pulmonary hemorrhages and edema, and massive atrial dilation in mice that died after lethal ip or iv doses of secalonic acid D [4].

Analytical, diagnostic and therapeutic context of Secalonic acid D

• Secalonic acid D amounts ranged from 0.3 to 4.5 ppm (0.3 to 4.5 micrograms/g), as determined by reversed-phase high-performance liquid chromatography [19].
• Suckling mice exposed to secalonic acid D (SAD) mycotoxin postnatally (by gavaging dams with 0, 15 or 25 mg/kg on postgestational days 1 to 10) or prenatally (by gavaging with 25 mg/kg on gestational day 13 to produce a positive behavioral teratogenic control group) manifested subtle preweaning neurobehavioral, neurochemical and growth deficits [20].
• Enzyme-linked immunosorbent assay for secalonic acid D [21].

References