Protective effects of glutathione on 5-fluorouracil-induced myelosuppression in mice.
The protective effects of glutathione (GSH) administration on myelosuppression induced by 5-fluorouracil (5-FU) were investigated in female BALB/c mice. Animals were allocated to four groups (16 mice/group). GSH was given orally at a dose of 800 mg/kg to groups 3 and 4 for 21 consecutive days (day 0 to day 20). 5-FU was repeatedly administered at a dose of 40 mg/kg to groups 2 and 3 for 1 week (day 7 to day 13) by gavage. Group 3 served as a combined treatment group and group 1 as a non-treated control group. The total observation period was 3 weeks. Body weight was measured once a week. A decrease in body weight due to 5-FU treatment was observed in groups 2 and 3 on day 14. Although the body weight in group 2 had not increased by 1-week after cessation of 5-FU treatment, the value in group 3 markedly recovered. Hematology, total nucleated myelocyte count and histopathology of bone marrow were carried out on day 14 and day 21. In groups 2 and 3, these examinations showed thrombocytopenia, leukopenia, reticulocytopenia and myelosuppression on day 14. However, platelets and bone marrow were less affected in group 3 than in group 2. On day 21, the thrombocytopenia in groups 2 and 3 was resolved. The myelosuppression, leukopenia and reticulocytopenia resolved in group 3, but not in group 2. Although simple microcytic anemia occurred delayed on day 21, it was less severe in group 3 than in group 2. Therefore, GSH may have preventive effects against 5-FU-induced hematopoietic toxicity, and accelerate recovery after cessation of 5-FU treatment.
Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 2548 Fujimagari, Ube, Yamaguchi 755-8501, Japan.
Seiji
S
Kojima
Katsumi
K
Takaba
Naoya
N
Kimoto
Tsuyoshi
T
Takeda
Masakazu
M
Kakuni
Masato
M
Mizutani
Kazuo
K
Suzuki
Hitoshi
H
Sato
Takuji
T
Hara
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D004336:Drug Antagonism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D005978:Glutathione / Q000008:administration & dosage / Q000494:pharmacology*; D006402:Hematologic Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006403:Hematologic Tests; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C
D007166:Immunosuppressive Agents; D005978:Glutathione; D005472:Fluorouracil