Hypoglycemia in Mice Administered With Fusarenon-X

Shimizu, Tsutomu; Nakano, Naoko; Matsui, Tadaaki; Aibara, Kageaki

doi:10.7883/yoken1952.32.189

Cited by 5 publications

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“…In studying toxicity of intraperitoneally (ip) administered FX in mice, Shimizu et al found rapidly developing hypoglycemia and cell death in the intestinal crypt cells after 2 hr postadministration (PA) [16]. In preliminary study of FX-intoxication, we have ascertained that the same kind of cell death is observed in rat stomach and that vulnarability of the stomach is higher in rats than in mice as reported formerly [14,19].…”

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confidence: 57%

Rapid Apoptotic Changes in the Gastric Glandular Epithelium of Rats Administered Intraperitoneally with Fusarenon-X.

Shimizu

Miyoshi

et al. 1997

The Journal of Veterinary Medical Science

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ABSTRACT. Fusarenon-X (FX) 1.5 mg/kg was administered intraperitoneally (ip) to 6-week-old male Wistar rats for examination of pathologic effects on the glandular stomach. Rats ip-treated with sterilized physiological saline were used as control. FX-administered rats showed dilatation of the stomach with increased fluid contents after 1-4 hr. Light microscopically, a few apoptotic karyopyknosis were seen in chief cells in the basal region at 1 hr postadministration (PA) and mitotic inhibition was evident after 2 hr PA. Marked apoptosis of nuclear pyknosis and cytoplasmic inclusions in both zymogenic and oxyntic cells developed from basal to middle regions of the gastric mucous membrane at 2-4 hr PA with a peak at 3 hr. Apoptotic changes of differentiating neck cells and surface epithelia were less evident. Electron microscopy revealed that the chief cells were the main target of FX-induced apoptotosis. The parietal cells were secondarily involved because they phagocytosed chief cell-derived apoptotic bodies. In situ detection of DNA breaks by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction revealed the positive nuclei after 1 hr PA, which increased with time and reached a peak at 3 hr PA, in accordance with apoptotic changes in histological study. Agarose gel electrophoresis of DNA isolated from the gastric mucosae of FX-administered rats showed ladder pattern of DNA fragments after 1.5 hr PA with the maximum distinctness at 3 hr PA. -KEY WORDS: apoptosis, DNA fragmentation, fusarenon-X, rat stomach, TUNEL.

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confidence: 57%

Rapid Apoptotic Changes in the Gastric Glandular Epithelium of Rats Administered Intraperitoneally with Fusarenon-X.

Shimizu

Miyoshi

et al. 1997

The Journal of Veterinary Medical Science

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“…In a study on the toxicity of intraperitoneally (ip) administered FX in mice, Shimizu et al found rapidly developing hypoglycemia and cell death in the intestinal crypt cells at 2 hr postadministration (PA) [19]. In both rats and mice, intestinal crypt cell damage caused by sublethal toxic doses of FX was rapid and severe when administered ip, whereas it was slight to moderate when administered perorally (po) (unpublished data).…”

Section: Animalsmentioning

confidence: 99%

Course of Apoptotic Changes in the Rat Gastric Mucosa Caused by Oral Administration of Fusarenon-X.

Shimizu

1997

J. Vet. Med. Sci.

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ABSTRACT. Male 5-week-old Wistar rats orally (po) administered with fusarenon-X (FX) 1.5 mg/kg and control rats po-treated with distilled water were sacrificed at 0-48 hr after gavage. FX-administered rats showed significant dilatation of the stomach with increased fluid contents at 1-24 hr postadministration (PA). Histopathologically, karyopyknosis of chief cells in the basal region of the gastric glands began to appear at 1 hr, and nuclear fragments were seen in the neck cell region at 1.5 hr PA. At 2-4 hr PA, apoptotic cells appeared diffusely in the neck region and focally in the basal region. Electron microscopy revealed that cells phagocytosing apoptotic bodies were the surface epithelia, undifferentiated neck cells, parietal cells and chief cells. No evidence was detected to show that parietal cells underwent apoptotic changes. The apoptotic lesions peaked at 4-6 hr PA, gradually subsided at 12 hr PA, and became minimal leaving apoptotic remnants in the basal region at 24 hr PA. At 48 hr PA, however, diffuse apoptotic lesions reappeared in the basal region at a level similar to that at 2-3 hr PA. This might be attributable to absorption of FX retaining in the stomach for 24 hr. In situ detection of DNA breaks by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction was consistent with the histopathologic findings. Agarose gel electrophoresis of DNA fragments isolated from the gastric mucosae of FX-administered rats showed a ladder pattern after 1.5 hr PA and the pattern became more distinct at 2-4 hr PA. -KEY WORDS: apoptosis, DNA fragmentation, fusarenon-X, oral administration, rat stomach.J. Vet. Med. Sci. 59(3): 191-199, 1997 MATERIALS AND METHODS Animals:A hundred and four male 5-week-old Wistar rats weighing 140 ± 10.0 g purchased from the Kumamoto Agency of Japan SLC Co., Ltd., Shizuoka, Japan were randomly divided into the respective experimental and control groups for examination of pathomorphological changes and DNA fragmentation of the glandular stomach in rats po-treated with FX. They were kept in cages each containing 4 or 5 animals. Commercial breeder pellets for rats and mice (Japan Agricultural Products Co., Ltd., Yokohama) and tap water were given ad libitum. The room temperature and humidity during the experiment were conditioned 24 ± 1.0°C and 50-60%.Toxin administration: Each rat of the experimental group was po administered with 1.5 mg/kg of FX (purity 97.4%, Wako Pure Chemical Industries Ltd., Osaka) dissolved in distilled water at 0.5 mg/ml. The control group received po 0.5 ml of distilled water.Pathomorphological examination: Eighty rats, consisting of the equal number of FX-treated and control groups were sacrificed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, and 48 hr PA of the toxin by exsanguinating from the jugular vein under light ether anesthesia: each 4 animals for 0 to 4 hr and each 3 for 6 to 48 hr PA. The stomach with contents was removed and weighed using Mettler P1200 (Mettler Inc., Darmstadt, Germany). Data were analyzed using Stude...

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“…administration [ 29 ] and 1.5 hr after ingestion [ 28 ]. FX disrupted glycolysis and induced intestinal malabsorption by causing hypoglycemia and inhibiting mitosis of intestinal crypt cells [ 53 ]. Furthermore, FX damaged the active transport system of monosaccharides and impaired diffusional movements between the intestinal epithelial layer and mesenteric vein [ 27 ].…”

Section: Toxicitymentioning

confidence: 99%

An overview of the toxicology and toxicokinetics of fusarenon-X, a type B trichothecene mycotoxin

Aupanun

Poapolathep

Giorgi

et al. 2017

The Journal of Veterinary Medical Science

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Fusarenon-X (FX) is a type B trichothecene mycotoxin that is frequently observed along with deoxynivalenol (DON) and nivalenol (NIV) in agricultural commodities. This review aims to give an overview of the literature concerning the toxicology and toxicokinetics of FX. FX is primarily found in cereals grown in temperate regions, but it can also be found worldwide because of the global transport of products. The major toxicity of FX occurs through inhibition of protein synthesis, followed by the disruption of DNA synthesis. Moreover, FX has also been shown to induce apoptosis in in vitro and in vivo studies. The targets of FX are organs containing actively proliferating cells, such as the thymus, spleen, skin, small intestine, testes and bone marrow. FX causes immunosuppression, intestinal malabsorption, developmental toxicity and genotoxicity. In addition, sufficient evidence of carcinogenicity in experimental animals is currently lacking, and the International Agency for Research on Cancer (IARC) classifies it as a group 3 carcinogen.

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Hypoglycemia in Mice Administered With Fusarenon-X

Cited by 5 publications

References 12 publications

Rapid Apoptotic Changes in the Gastric Glandular Epithelium of Rats Administered Intraperitoneally with Fusarenon-X.

Rapid Apoptotic Changes in the Gastric Glandular Epithelium of Rats Administered Intraperitoneally with Fusarenon-X.

Course of Apoptotic Changes in the Rat Gastric Mucosa Caused by Oral Administration of Fusarenon-X.

An overview of the toxicology and toxicokinetics of fusarenon-X, a type B trichothecene mycotoxin

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