Effect of pre-treatment with St John's Wort on nephrotoxicity of cisplatin in rats.
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.
Shibayama
Yoshihiko
Y
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Kawachi
Akio
A
Onimaru
Shunji
S
Tokunaga
Jin
J
Ikeda
Ryuji
R
Nishida
Kentaro
K
Kuchiiwa
Satoshi
S
Nakagawa
Shiro
S
Takamura
Norito
N
Motoya
Toshiro
T
Takeda
Yasuo
Y
Yamada
Katsushi
K
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
D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000970:Antineoplastic Agents; D008668:Metallothionein; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin