Role of renal prostaglandins in the modulation of cisplatinum nephrotoxicity

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5316331

Noordewier, B; Danielson, P W; Noordewier, E R; Bredehoeft, S J

Indomethacin (I) inhibition of renal prostaglandin (PG) synthesis potentiates the nephorotoxic effects of cis-dichlorodiamine platinum (Cis-Pt). The purpose of this study was to determine if this potentiation was unique to I or was shared by other inhibitors of PG synthesis. Male Fischer 344 rats were fed a purified diet replete (Repl) or deplete (Depl) in sodium. After 5 days on this diet, the rats were given saline or cis-Pt (10 mg/kg, iv) with or without tolmetin (Tol) (2 x 10 mg/kg, ip then iv). Toxicity was assessed 2 days after the injections. Cis-Pt given alone increased BUN and plasma creatinine (Cr) in both Depl (BUN = 43 mg/dl, Cr = 1.3 mg/dl) and Repl (BUN = 45, Cr = 1.3) groups. Tol produced a moderate increase in cis-Pt toxicity in Repl rats (BUN = 62, Cr = 1.5) and a marked increase in Depl rats (BUN = 138, Cr = 2.6). These biochemical changes were accompanied by concurrent changes in renal histology. Rats given cis-Pt alone had focal areas of toxicity marked by evidence of necrosis and vacuolation. Tol enhancement of toxicity was characterized by an increased extent of damage with the appearance of tubular protein and some mineralization. The effects of Tol mimic those of I indicating a role for renal prostaglandins in the renal toxicity of Cis-Pt.

• Research Organization: Univ. of North Dakota, Grand Forks
• OSTI ID: 5316331
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
ELEMENTS
KIDNEYS
KINETICS
MAMMALS
METALS
NECROSIS
ORGANS
PATHOLOGICAL CHANGES
PLATINUM
PLATINUM METALS
PROSTAGLANDINS
RATS
REACTION KINETICS
RODENTS
TOXICITY
TRANSITION ELEMENTS
VERTEBRATES