Effects of cisplatin and taxol on inducible nitric oxide synthase, gastrin and somatostatin in gastrointestinal toxicity.
Cisplatin (9 mg/kg) or taxol (20 mg/kg) treatment of Wistar rats produced a sharp decrease in inducible nitric oxide synthase (iNOS) and gastrin in the pyloric region of the stomach, and an increase in iNOS and somatostatin in the pancreatic islets. Nitric oxide (NO) functions as a relaxation factor in the smooth muscle of the muscularis mucosa while gastrin plays an important role in the gastroprotection of the mucosa through NO. It is proposed that a decline of the iNOS and gastrin after cisplatin or taxol treatments is related to distention of the stomach, and possibly nausea and vomiting. Hyperglycemia and glucose intolerance after cisplatin treatment may be caused by increases of somatostatin and iNOS in the pancreatic islets. Combination therapy with cisplatin and taxol seems to ameliorate various toxicities due to these two individual drugs.
Wang
Y
Y
Department of Zoology, Michigan State University, East Lansing 48824-1115, USA.
Aggarwal
S K
SK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000096:biosynthesis*; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005755:Gastrins; D013004:Somatostatin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017239:Paclitaxel; D002945:Cisplatin