Immunohistochemical localizations of secretin, cholecystokinin, and somatostatin in the rat small intestine after acute cisplatin treatment.
Cisplatin (CDDP) is an antitumor platinum complex that causes the well-studied side effect of renal tubular failure. In the present study, the acute effects of CDDP treatment on the localization of gut hormones in the rat small intestine were examined by immunohistochemistry. Male Sprague-Dawley rats were used for these experiments. Rats were injected intravenously with CDDP (3 mg/kg) in saline or were left untreated (control). After the rats were euthanized at 1, 3, 5, or 10 days after CDDP treatment, the small intestines (duodenum, jejunum, and ileum) were quickly removed, fixed, embedded in paraffin, and cut. No mucosal toxicity was detected by histopathological observation in any of the intestines of CDDP-treated rats. The immunohistochemical detection was performed using anti-secretin, anti-cholecystokinin (CCK), and anti-somatostatin with the avidin-biotin-immuno-peroxidase procedure. The total number of immunoreactive cells per complete cross-section was counted. In the duodenum, the numbers of secretin-immunoreactive cells and somatostatin-immunoreactive cells were dramatically increased 5 days after CDDP treatment. In the jejunum, the number of CCK-immunoreactive cells was increased 1 day after CDDP treatment and those of secretin-immunoreactive cells and CCK-immunoreactive cells were increased 5 days after CDDP treatment. In the ileum, the number of CCK-immunoreactive cells was increased 1 day after CDDP treatment. The change in the secretin-immunoreactive cell count may be caused by metabolic inhibition of gastrin following CDDP-induced nephrotoxicity. The change in the CCK-immunoreactive cell count may promote the excretion of bile. Therefore, somatostatin may regulate secretin and CCK secretion. We conclude that the distribution of these hormone-immunoreactive cells in the rat small intestine might be controlled by CDDP-induced nephrotoxicity without gut mucosal toxicity.
Miyamoto
Yohei
Y
Toxicology Laboratory, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa 248-8555, Japan. Youhei_Miyamoto@nts.toray.co.jp
Miyamoto
Mari
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002452:Cell Count; D002766:Cholecystokinin / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D007124:Immunoenzyme Techniques; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D013997:Time Factors
D000970:Antineoplastic Agents; D012633:Secretin; D013004:Somatostatin; D002766:Cholecystokinin; D003404:Creatinine; D002945:Cisplatin