Effects of polaprezinc on gastric mucosal damage and neurotransmitters in a rat model of chemotherapy-induced vomiting

J Int Med Res. 2018 Jun;46(6):2436-2444. doi: 10.1177/0300060518771492. Epub 2018 May 13.

Abstract

Objective To investigate the effects of polaprezinc (PZ) on cyclophosphamide (CTX)- or cisplatin (DDP)-induced gastric mucosal injury and on a rat model of neurotransmitter-mediated vomiting. Methods Sprague-Dawley rats were divided at random into Control, CTX, DDP, PZ+CTX, and PZ+DDP groups. After 20 days, brain tissues and sera were analyzed for the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and nuclear factor kappa B (NF-κB). Hematoxylin and eosin-stained sections of stomach, intestine, and brain tissues were examined using light microscopy. Results The levels of DA, 5-HT, and NF-κB in brain and serum samples of rats treated with CTX or DDP were significantly increased compared with those of rats in the Control group. There was a significant decrease in these values in the PZ group. Moreover, PZ reduced damage to brain tissue caused by CTX or DDP. Conclusions PZ decreased the levels of DA, 5-HT, and NF-κB in blood and brain tissues caused by CTX or DDP and reduced the chemotherapy-induced damage to the small intestine, stomach, and brain. These findings can be translated to the clinic to enhance the efficacy and safety of chemotherapy.

Keywords: 5-hydroxytryptamine; Polaprezinc; cancer chemotherapy; cisplatin; cyclophosphamide; dopamine; nuclear factor kappa B.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Anti-Ulcer Agents / pharmacology*
  • Anti-Ulcer Agents / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Brain / pathology
  • Brain Chemistry
  • Carnosine / analogs & derivatives*
  • Carnosine / pharmacology
  • Carnosine / therapeutic use
  • Cisplatin / adverse effects*
  • Cyclophosphamide / adverse effects*
  • Disease Models, Animal
  • Dopamine / analysis
  • Dopamine / blood
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / injuries
  • Gastric Mucosa / pathology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / injuries
  • Intestinal Mucosa / pathology
  • Intestine, Small / drug effects
  • Intestine, Small / injuries
  • Intestine, Small / pathology
  • Male
  • NF-kappa B / analysis
  • NF-kappa B / blood
  • Neurotransmitter Agents / analysis
  • Neurotransmitter Agents / blood
  • Organometallic Compounds / pharmacology*
  • Organometallic Compounds / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / analysis
  • Serotonin / blood
  • Vomiting / chemically induced*
  • Vomiting / pathology
  • Zinc Compounds / pharmacology
  • Zinc Compounds / therapeutic use

Substances

  • Anti-Ulcer Agents
  • Antineoplastic Agents
  • NF-kappa B
  • Neurotransmitter Agents
  • Organometallic Compounds
  • Zinc Compounds
  • polaprezinc
  • Serotonin
  • Carnosine
  • Cyclophosphamide
  • Cisplatin
  • Dopamine