Protective effect of N-benzyl-D-glucamine dithiocarbamate against cis-diamminedichloroplatinum-induced toxicity in gastrointestinal tract and bone marrow in rats.
The protective effect of N-benzyl-D-glucamine dithiocarbamate (BGD) against gastrointestinal and bone marrow toxicities produced by cis-diamminedichloroplatinum (DDP) injection in rats was studied. Rats were injected i.p. with BGD (2 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg). A scanning electron micrograph of the jejunum after DDP treatment showed damage in the villi, and that BGD protected the DDP-induced jejunal damage. BGD treatment also had a protective effect against DDP-induced diarrhea. BGD significantly reversed the reduction in maltase and sucrase activities of jejunal mucosa of rats treated with DDP. Platinum (Pt) concentrations in the gastrointestine as well as in the kidney and liver after DDP injection decreased following BGD treatment. The reduction of leukocytes following DDP injection returned to control values after BGD treatment. Biliary and urinary excretions of Pt after DDP injection was remarkably increased by BGD treatment. The results of this study indicated that the injection of BGD to rats treated with DDP can effectively remove Pt from the body through biliary and urinary excretions, resulting in protection of the gastrointestinal and bone marrow toxicities induced by DDP treatment.
Kojima
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Inoue
T
T
Kiyozumi
M
M
Shimada
H
H
D000818:Animals; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D002614:Chelating Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000037:antagonists & inhibitors*; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013859:Thiocarbamates / Q000627:therapeutic use*
D002614:Chelating Agents; D013859:Thiocarbamates; D013012:Sorbitol; C048763:N-benzylglucamine dithiocarbamate; D002945:Cisplatin