Preventive effect of oral goshajinkigan on chronic oxaliplatin-induced hypoesthesia in rats.

Abstract

Oxaliplatin, a widely used chemotherapeutic agent, induces peripheral neuropathy that manifests itself as two distinct phases: acute cold hyperesthesia and chronic peripheral hypoesthesia/dysesthesia. The latter is a serious dose-limiting side effect that can often lead to withdrawal of treatment. We have developed a rat model expressing both phases and used the model to investigate the action of goshajinkigan (GJG), a traditional Japanese herbal medicine, which was reported to ameliorate oxaliplatin-induced neuropathy in a placebo-controlled double-blind randomized phase II study. In this study, neuropathy was induced by injection of oxaliplatin twice weekly for 8 wks. The maximum level of cold hyperesthesia was observed at 4 wks with heat hypoesthesia developing later. Microscopy studies revealed atrophy of axons of myelinated sciatic nerve fibers in oxaliplatin-treated rats at 8 wks. Co-administration of GJG ameliorated both abnormal sensations as well as histological damage to the sciatic nerve. A pharmacokinetic study revealed numerous neuroprotective components of GJG that are rapidly absorbed into the blood. GJG and some of its components attenuated the generation of oxaliplatin-induced reactive oxygen species, which is a possible mechanism of oxaliplatin-induced neurotoxicity. The present study provides a useful animal model for oxaliplatin-induced neurotoxicity as well as a promising prophylactic agent.

• Authors: Toru Kono, Yasuyuki Suzuki, Keita Mizuno, Chika Miyagi, Yuji Omiya, Hitomi Sekine, Yasuharu Mizuhara, Kanako Miyano, Yoshio Kase, Yasuhito Uezono
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 16078 (Nov 06 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26542342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drugs, Chinese Herbal
• Neuroprotective Agents
• Organoplatinum Compounds
• gosha-jinki-gan
• Oxaliplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Atrophy (chemically induced, drug therapy)
• Axons (drug effects)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Ganglia, Spinal (drug effects)
• Herbal Medicine (methods)
• Hypesthesia (chemically induced, drug therapy)
• Male
• Medicine, East Asian Traditional (methods)
• Nerve Fibers, Myelinated (drug effects)
• Neuroprotective Agents (pharmacology)
• Neurotoxicity Syndromes (drug therapy)
• Organoplatinum Compounds (adverse effects)
• Oxaliplatin
• Peripheral Nervous System Diseases (chemically induced, drug therapy)
• Phytotherapy (methods)
• Rats
• Rats, Sprague-Dawley