title: 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.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, W-6, N-12, Kita-ku, Sapporo 060-0812, Japan.|Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, 3-1, N-33, E-14, Higashi-ku, Sapporo 065-0033, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Miyagi
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Omiya
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sekine
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Mizuhara
authors.affiliation: Division of Cancer Pathophysiology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Miyano
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
authors.affiliation: Division of Cancer Pathophysiology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001284:Atrophy / Q000139:chemically induced / Q000188:drug therapy; D001369:Axons / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects; D029001:Herbal Medicine / Q000379:methods; D006987:Hypesthesia / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008518:Medicine, East Asian Traditional / Q000379:methods; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy; D008517:Phytotherapy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; C119642:gosha-jinki-gan; D000077150:Oxaliplatin