Yamamoto Yutaro, Ura Kanae, Matsukawa Takuma, Saita Tetsuya, Shin Masashi
Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Acta Histochem Cytochem. 2022 Dec 28;55(6):185-192. doi: 10.1267/ahc.22-00032. Epub 2022 Dec 15.
We investigated the pharmacokinetics of alogliptin (AG) at the cell and tissue level in healthy Wistar rats and a type 2 diabetic Goto-Kakizaki (GK) rat model. Immunohistochemistry of the renal tissue in these rats, post 1 hr of AG administration, showed that the signal was observed in the glomeruli, proximal tubule S3 segments, distal tubules, collecting ducts, and only in the brush border of the epithelial cells of the proximal tubule S1, S2 segments. After 6 hr of AG administration, the staining intensity of the regions other than the S3 segments was considerably reduced in Wistar rats, with no change observed in GK rats. At 24 hr, the staining intensity was considerably reduced, even in GK rats; however, the staining of the S3 segment remained unaltered in both. Hepatocytes in zone III of the hepatic lobule were more intensely stained than those in zone I in Wistar rats at 1 hr. However, almost no staining was observed in the hepatocytes of GK rats at 1 hr. Complete loss of signal was observed in the hepatocytes of the Wistar rats after 6 hr. This study revealed that the pharmacokinetics of AG in GK rats are different from those in Wistar rats.
我们在健康的Wistar大鼠和2型糖尿病Goto-Kakizaki（GK）大鼠模型中，研究了阿格列汀（AG）在细胞和组织水平的药代动力学。在AG给药1小时后，对这些大鼠的肾组织进行免疫组织化学分析，结果显示在肾小球、近端小管S3段、远端小管、集合管以及仅在近端小管S1、S2段上皮细胞的刷状缘观察到信号。在AG给药6小时后，Wistar大鼠中除S3段外的其他区域的染色强度显著降低，而GK大鼠中未观察到变化。在24小时时，即使在GK大鼠中染色强度也显著降低；然而，两者的S3段染色均保持不变。在1小时时，Wistar大鼠肝小叶III区的肝细胞染色比I区的肝细胞更强。然而，在1小时时GK大鼠的肝细胞中几乎未观察到染色。6小时后Wistar大鼠的肝细胞中信号完全消失。这项研究表明，AG在GK大鼠中的药代动力学与Wistar大鼠不同。
