Pathological analysis of lesions in the exocrine pancreas of rats induced by Zinc Maltol

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  • Fujiwara Sakura
    Department of Drug Safety Research, Preclinical Research, Tokushima Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0192, Japan
  • Moroki Takayasu
    Department of Drug Safety Research, Preclinical Research, Tokushima Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0192, Japan
  • Hitomi Masaya
    Department of Drug Safety Research, Preclinical Research, Tokushima Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0192, Japan
  • Sato Makoto
    Department of Drug Safety Research, Preclinical Research, Tokushima Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0192, Japan
  • Terayama Yui
    Department of Drug Safety Research, Preclinical Research, Tokushima Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0192, Japan
  • Yoshikawa Tsuyoshi
    Department of Drug Safety Research, Preclinical Research, Tokushima Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0192, Japan

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<p> The pancreas plays an important role in the homeostasis of zinc (Zn), a nutritionally essential metal. In several previous studies, Zn ions induced inflammatory changes in the exocrine pancreas; however, little is known about Zn complexes. In this study, we microscopically, immunohistochemically, and ultrastructurally examined pancreatic lesions in Sprague-Dawley (SD) rats induced by a 4-week repeated oral dose toxicity study of Zinc Maltol (ZM), a zinc (II) complex. ZM induces acinar atrophy and increases the number of duct-like structures. Immunohistochemistry revealed a decrease in the number of trypsin-positive cells, and an increase in the number of SOX9-positive cells. Interstitial fibrosis and macrophage infiltration also correlated with the degree of acinar atrophy. Electron microscopic evaluation revealed that the acinar cells that lost granules were surrounded by fibroblasts and collagen fibers. In conclusion, we provided a detailed description of ZM-induced pancreatic lesions in SD rats.</p>

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