Immunohistochemical Localization of Alogliptin, a DPP-4 Inhibitor, in Tissues of Normal and Type 2 Diabetes Model Rat.

IF 1.6 4区生物学 Q4 CELL BIOLOGY

Acta Histochemica Et Cytochemica Pub Date : 2022-12-28 DOI:10.1267/ahc.22-00032

Yutaro Yamamoto, Kanae Ura, Takuma Matsukawa, Tetsuya Saita, Masashi Shin

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Abstract

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.

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DPP-4抑制剂阿格列汀在正常和2型糖尿病模型大鼠组织中的免疫组织化学定位

我们在健康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)在细胞和组织水平上的药代动力学。AG给药1小时后，对大鼠肾组织进行免疫组化，结果显示肾小球、近端小管S3段、远端小管、集合管均可见信号，近端小管S1、S2段上皮细胞刷状缘可见信号。AG给药6小时后，Wistar大鼠除S3节段外其他区域的染色强度明显降低，而GK大鼠未见变化。24小时时，即使在GK大鼠中，染色强度也明显降低;然而，两者S3节段的染色保持不变。Wistar大鼠肝小叶III区肝细胞在1小时时染色较I区肝细胞强烈。而GK大鼠肝细胞在1小时后几乎未见染色。6小时后观察到Wistar大鼠肝细胞完全丧失信号。本研究发现AG在GK大鼠和Wistar大鼠体内的药代动力学存在差异。

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来源期刊

Acta Histochemica Et Cytochemica 生物-细胞生物学

CiteScore

3.50

自引率

8.30%

发文量

审稿时长

>12 weeks

期刊介绍： Acta Histochemica et Cytochemica is the official online journal of the Japan Society of Histochemistry and Cytochemistry. It is intended primarily for rapid publication of concise, original articles in the fields of histochemistry and cytochemistry. Manuscripts oriented towards methodological subjects that contain significant technical advances in these fields are also welcome. Manuscripts in English are accepted from investigators in any country, whether or not they are members of the Japan Society of Histochemistry and Cytochemistry. Manuscripts should be original work that has not been previously published and is not being considered for publication elsewhere, with the exception of abstracts. Manuscripts with essentially the same content as a paper that has been published or accepted, or is under consideration for publication, will not be considered. All submitted papers will be peer-reviewed by at least two referees selected by an appropriate Associate Editor. Acceptance is based on scientific significance, originality, and clarity. When required, a revised manuscript should be submitted within 3 months, otherwise it will be considered to be a new submission. The Editor-in-Chief will make all final decisions regarding acceptance.