A mycotoxin
Moniliformin induces mitotic arrest at the metaphase stage.
Mitosis is a part of the cell cycle when replicated chromosomes are separated into two new nuclei. The process of mitosis is divided into stages corresponding to the completion of one set of activities and the start of the next.
In vitro: Moniliformin, first isolated as a mycotoxin from Fusarium moniliforme, was found to be phytotoxic and arrests mitosis of maize root meristematic cells at the metaphase stage. The mitotic spindle could be disrupted by the treatment of moniliformin, but no direct effect on tubulin had been observed [1].
In vivo: A previous study was conducted on rat heart to in situ determine the myocardial toxicity of moniliformin, originally isolated from mouldy corn and soil samples in the Keshan disease prevalent area in China. Results showed that perfusion of moniliformin 10-7 mol/liter in isolated heart decreased myocardial contractile force by 52%. Intravenous injection of moniliformin at 1/6 and 1/4 LD50 could markedly inhibit cardiac hemodynamic variables associated with myocardial contractile function. Moreover, moniliformin was able to decrease +/- LV dP/dt max by 52%, and induce ventricular arrhythmia. These findings indicated that moniliformin was toxic to mammalian heart and might be an important factor relative to Keshan disease [2].
Clinical trial: So far, no clinical study has been conducted.
参考文献:
[1] Duke, S.?O. and Dayan, F.E. Modes of action of microbially-produced phytotoxins. Toxins (Basel) 3(8), 1038-1064 (2011).
[2] Fan LL, Li J, Sun LH.? Effect of moniliformin on myocardial contractility in rats. Biomed Environ Sci. 1991 Sep;4(3):290-4.
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Animal experiment: |
Rats: Moniliformin is prepared in water. In this experiment, 5 dose groups (3, 6, 9, 12 and 15 mg/kg moniliformin b.w.) of test animals are exposed to moniliformin for 28 days. Each group consists of 5 male Sprague-Dawley rats. The dose groups are determined based on our acute toxicity study of MON in rats. In addition, a control group administered with filtered tap water and two satellite groups (dosed 12 and 15 mg/kg b.w. moniliformin) are used. The two satellite groups are kept alive for an additional 14 days without treatment to detect possible delayed toxic effects and to follow up recovery[3]. Mice: Sterile aqueous solutions of moniliformin are injected intraperitoneally (0.2 mL) into five female and five male white mice, weighing about 25 g each, at concentrations equivalent to 0, 20, 25, 30, and 35 mg per kg of body weight. The mice are observed over a 4-day period, and LD50 values are determined[1]. |
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参考文献: [1]. Burmeister HR, et al. Moniliformin, a metabolite of Fusarium moniliforme NRRL 6322: purification and toxicity. Appl Environ Microbiol. 1979 Jan;37(1):11-3. |
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