Possible (enzymatic) routes and biological sites for metabolic reduction of BNP7787, a new protector against cisplatin-induced side-effects

Biochemical Pharmacology

Volumn 68, Issue 3, 2004, Pages 493-502

  Verschraagen, Miranda ^a   Boven, Epie ^a   Torun, Emine ^a   Hausheer, Frederick H ^b   Bast, Aalt ^c   Van Der Vijgh, Wim J F ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b BioNumerik Pharmaceuticals Inc   (United States)

^c MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

BNP7787; glutathione; glutathione reductase; GR; GSH; GSSG; Mesna; NADPH; nicotinamide adenine dinucleotide phosphate; oxidized glutathione; PBS; phosphate buffered saline; RBC; red blood cell; thioredoxin reductase; TrxR; Vrije Universiteit medical center; VUmc

Indexed keywords

CISPLATIN; CYSTEINE; DIMESNA; DISODIUM 2,2' DITHIOBIS ETHANE SULFONATE; GLUTAREDOXIN; GLUTATHIONE; PROTECTIVE AGENT; THIOREDOXIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD; CHEMOPROPHYLAXIS; CONTROLLED STUDY; CYTOSOLIC FRACTION; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG INDUCED DISEASE; DRUG MECHANISM; DRUG POTENCY; ENZYME ACTIVITY; ERYTHROCYTE; IN VIVO STUDY; KIDNEY CORTEX; LIVER; NEPHROTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTECTION; RADIATION DETECTION; RAT; SMALL INTESTINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CISPLATIN; CYSTEINE; CYTOSOL; ELECTROCHEMISTRY; ENZYMES; ERYTHROCYTES; GLUTATHIONE; HUMANS; MESNA; PROTECTIVE AGENTS; RATS; TISSUE DISTRIBUTION;

EID: 3042779809     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2004.04.005     Document Type: Article

References (22)

1. Hausheer F.H., Kanter P., Cao S., Haridas K., Seetharamulu P., Reddy D., et al. Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents. Semin. Oncol. 25:1998;584-599
2. Hausheer F.H., Kochat H., Parker A.R., Ding D., Yao S., Hamilton S.E., et al. New approaches to drug discovery and development: a mechanism-based approach to pharmaceutical research and its application to BNP7787, a novel chemoprotective agent. Cancer Chemother. Pharmacol. 52:2003;S3-S15
3. Boven E., Verschraagen M., Hulscher T.M., Erkelens C.A.M., Hausheer F.H., Pinedo H.M., et al. BNP7787, a novel protector against platinum-related toxicities, does not affect the efficacy of cisplatin or carboplatin in human tumour xenografts. Eur. J. Cancer. 38:2002;1148-1156
4. Verschraagen M, Boven E, Torun E, Erkelens CAM, Hausheer FH, Van der Vijgh WJF. Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats. Br J Cancer, in press.
5. Verschraagen M., Kedde M.A., Hausheer F.H., Van der Vijgh W.J.F. The chemical reactivity of BNP7787 and its metabolite mesna with the cytostatic agent cisplatin: comparison with the nucleophiles thiosulphate, DDTC, glutathione and its disulfide GSSG. Cancer Chemother. Pharmacol. 51:2003;499-504
6. Leeuwenkamp O.R., Neijt J.P., Van der Vijgh W.J., Pinedo H.M. Reaction kinetics of cisplatin and its monoaquated species with the modulating agents (di)mesna and thiosulphate. Eur. J. Cancer. 27:1991;1243-1247
7. Bast A., Haenen G.R.M.M., Savenije-Chapel E.M. Inhibition of rat hepatic microsomal lipid peroxidation by mesna via glutathione. Arzneim-Forsch/Drug Res. 37(II):1987;1043-1045
8. Mashiach E., Sela S., Weinstein T., Cohen H.I., Shasha S.M., Kristal B. Mesna: a novel renoprotective antioxidant in ischaemic acute renal failure. Nephrol. Dial Transpl. 16:2001;542-551
9. Goren M.P., Hsu L.C., Li J.T. Reduction of dimesna to mesna by the isolated perfused rat liver. Cancer Res. 58:1998;4358-4362
10. Ormstad K., Uehara N. Renal transport and disposition of Na-2-mercaptoethane sulfonate disulfide (dimesna) in the rat. FEBS Lett. 150:1982;354-358
11. Ormstad K., Orrenius S., Låstbom T., Uehara N., Pohl J., Stekar J., et al. Pharmacokinetics and metabolism of sodium 2-mercaptoethanesulfonate in the rat. Cancer Res. 43:1983;333-338
12. Rozell B., Hansson H.A., Luthman M., Holmgren A. Immunohistochemical localization of thioredoxin and thioredoxin reductase in adult rats. Eur. J. Cell Biol. 38:1985;79-86
13. Rundlöf A.-K., Carlsten M., Giacobini M.M.J., Arner E.S.J. Prominent expression of the selenoprotein thioredoxin reductase in the medullary rays of the rat kidney and thioredoxin reductase mRNA variants differing at the 5′ untranslated region. Biochem. J. 347:2000;661-668
14. Holmgren A. Enzymatic reduction-oxidation of protein disulfides by thioredoxin. Methods Enzymol. 107:1984;295-300
15. Arscott L.D., Gromer S., Schirmer R.H., Becker K., Williams C.H. The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 94:1997;3621-3626
16. Verschraagen M., Zwiers T.H.U., Torun E., Donker M.G., Reinhoud N.J., Van der Vijgh W.J.F. Simultaneous determination of BNP7787 and its metabolite mesna in plasma and tissue by micro-HPLC with a dual electrochemical detector. J. Pharm. Sci. 92:2003;1040-1050
17. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:1976;248-254
18. Verschraagen M., Zwiers T.H.U., Bosma M., Torun E., Van der Vijgh W.J.F. Quantification of mesna and total mesna in kidney tissue by high-performance liquid chromatography with electrochemical detection. J. Chromatogr. B. 783:2003;33-42
19. Ormstad K., Ohno Y. N-Acetylcysteine and sodium 2-mercaptoethane sulfonate as sources of urinary thiol groups in the rat. Cancer Res. 44:1984;3797-3800
20. Reuther H., Kohl M., Wildenauer D.B. The interactions of mesna and dimesna with the sulfate exchange in human red blood cells. Arzneim-Forsch/Drug Res. 36:1986;763-765
21. James S.P. The biochemistry of endogenous organosulphur compounds. Drug Metabol. Drug Interact. 6:1988;167-182
22. Holmgren A., Bjornstedt M. Thioredoxin and thioredoxin reductase. Methods Enzymol. 252:1995;199-208