title: Effect of pre-treatment with St John's Wort on nephrotoxicity of cisplatin in rats.
abstract: An herbal health care supplement, St John's Wort (SJW, Hypericum perforatum) has become widely used in the treatment of depression, and is known to interact with therapeutic drugs. Here we report a preventive effect of SJW on cisplatin nephrotoxicity in rats. Rats were given SJW (400 mg/kg/day, p.o.) for 10 consecutive days, and were injected with cisplatin (5 mg/kg, i.v.) on the day after the final SJW treatment. Cisplatin treatment increased the serum creatinine level, which is an index of nephrotoxicity, to 1.51+/-0.22 mg/dl (mean+/-SE) from 0.28+/-0.05 mg/dl (control) on day 5 after the cisplatin injection. This increase fell significantly to 0.86+/-0.13 mg/dl by pre-treatment with SJW. Cisplatin-induced histological abnormality of the kidney was blocked by pre-treatment with SJW. When SJW was administered for 10 days, the amounts of renal metallothionein (MT) and hepatic multidrug resistance protein 2 (Mrp2) were increased to 164.8+/-13.0% and 220.8+/-39.3% (mean+/-SE) of controls, respectively. GSH levels in the kidney and liver were not changed. Total and free cisplatin concentration in serum was not influenced by SJW treatment. In conclusion, the results suggest that pre-treatment with SJW may diminish cisplatin nephrotoxicity.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shibayama
authors.forename: Akio
authors.initials: A
authors.lastname: Kawachi
authors.forename: Shunji
authors.initials: S
authors.lastname: Onimaru
authors.forename: Jin
authors.initials: J
authors.lastname: Tokunaga
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ikeda
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuchiiwa
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Norito
authors.initials: N
authors.lastname: Takamura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Motoya
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D020902:Hypericum; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000970:Antineoplastic Agents; D008668:Metallothionein; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin