Effect of dimethyl sulfoxide (DMSO) on cis-Pt induced changes in renal microvillar enzymes
Journal Article
·
· FASEB Journal (Federation of American Societies for Experimental Biology); (USA)
OSTI ID:6929560
- Univ. of North Dakota, Grand Forks (USA)
Cis-diamminedichloroplatinum (cis-Pt) is an antitumor agent with known nephrotoxic effects. We studied cis-Pt effects on five renal microvillar enzymes. Further, because the nephrotoxic effects of cis-Pt have been associated with O{sub 2}-derived free radicals, we studied the effect of the hydroxyl radical scavenger DMSO on observed enzyme changes. Male, weanling Sprague-Dawley rats were fed a purified diet and water with or without DMSO (4.75%). After 35 days they were given (iv) either cis-Pt (7.5 mg/kg) or saline in a 2{times}2 design. Rats were killed 4 days post-injection. Compared to saline-treated rats, Pt-treated animals showed increased blood urea nitrogen (BUN), plasma creatinine (Cr), liver and kidney minerals (including Zn) and increased activity of renal microvillar angiotensin converting enzyme (ACE). Cis-Pt decreased the activity of gamma glutamyl transferase (GGT), alkaline phosphatase (AP) and endopeptidase (EP) and had no effect on aminopeptidase (AMP). DMSO attenuated cis-pt-mediated BUN and Cr changes, independently increased ACE activity, showed significant inhibition of cis-Pt effects on GGT and AP and had no effect on EP or AP activities. We conclude that cis-Pt-mediated microvillar enzyme changes may be related, in some cases, to renal Zn levels and, in others, to damage by hydroxyl radical.
- OSTI ID:
- 6929560
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (USA), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (USA) Vol. 3:3; ISSN FAJOE; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BODY
COMPLEXES
ELEMENTS
ENZYME ACTIVITY
HYDROXYL RADICALS
INHIBITION
KIDNEYS
MAMMALS
METALS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PLATINUM COMPLEXES
RADICALS
RATS
RODENTS
SCAVENGING
TOXICITY
TRANSITION ELEMENT COMPLEXES
VERTEBRATES
ZINC
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BODY
COMPLEXES
ELEMENTS
ENZYME ACTIVITY
HYDROXYL RADICALS
INHIBITION
KIDNEYS
MAMMALS
METALS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PLATINUM COMPLEXES
RADICALS
RATS
RODENTS
SCAVENGING
TOXICITY
TRANSITION ELEMENT COMPLEXES
VERTEBRATES
ZINC