Lack of nephrotoxicity of oral ammine/amine platinum (IV) dicarboxylate complexes in rodents

McKeage, Mark J.; Morgan, SE; Boxall, Fe; Murrer, Barry A.; Hard, GC; Harrap, K. R.

doi:10.1038/bjc.1993.182

Cited by 37 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rat model of cisplatin-induced nephrotoxicity is considered to be sensitive and reproducible system (Heidemann et al, 1989;McKeage et al, 1993;Badary et al, 1997a,b) The current study demonstrates that NAR provides protection against cisplatin-induced nephrotoxicity in rats.…”

Section: Discussionmentioning

confidence: 66%

“…Cisplatin has been shown to cause nephrotoxicity in patients (DeConti et al, 1973;Daugaard et al, 1988) as well as in a variety of animal species (McKeage et al, 1993;Badary et al, 1997a,b). The rat model of cisplatin-induced nephrotoxicity is considered to be sensitive and reproducible system (Heidemann et al, 1989;McKeage et al, 1993;Badary et al, 1997a,b) The current study demonstrates that NAR provides protection against cisplatin-induced nephrotoxicity in rats.…”

Section: Discussionmentioning

confidence: 97%

“…The effects of cisplatin were similar to those previously described (Heidemann et al, 1989;McKeage et al, 1993;Rybak et al, 1995; NAR was given by gastric tube (20 mg/kg/day) 5 days before a single i.v. cisplatin (7 mg/kg) and thereafter throughout the experiment.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Naringenin attenuates cisplatin nephrotoxicity in rats

et al. 2005

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Naringenin attenuates cisplatin nephrotoxicity in rats

et al. 2005

View full text Add to dashboard Cite

“…[142][143][144] The dose-limiting toxicity is myelosuppression, with both thrombocytopenia and leucopenia. !144.145] Emesis is mild and controlled by orally administered antiemetic drugS.…”

Section: Mckeagementioning

confidence: 99%

Comparative Adverse Effect Profiles of Platinum Drugs

1995

View full text Add to dashboard Cite

Since the discovery of the biologically active platinum complexes 30 years ago, 2 agents have become widely established in clinical oncology practice. Both cisplatin and carboplatin are platinum(II) complexes with 2 ammonia groups in the cis- position. However, they differ in their solubility, chemical reactivity, dichloride or alicyclic oxygenated leaving groups, pharmacokinetics and toxicology. Cisplatin causes severe renal tubular damage and reduces glomerular filtration, and requires concurrent saline hydration and mannitol diuresis to eliminate potentially lethal and unacceptable damage to the kidneys. Carboplatin, at conventional doses, causes no decrease in glomerular filtration and only minor transient elevations in urinary enzymes. Cisplatin is the most emetic cancer drug in common use, while nausea and vomiting associated with carboplatin are moderately severe. Serotonin release from enterochromaffin gut mucosal cells and stimulation of serotonin 5-HT3-receptors mediates acute emesis. Selective inhibitors of the 5-HT3-receptor protect against cisplatin- and carboplatin-induced nausea and vomiting. Peripheral neurotoxicity is the most dose-limiting problem associated with cisplatin. Loss of vibration sense, paraesthesia and sensory ataxia comes on after several treatment cycles. Carboplatin, however, is relatively free from peripheral neurotoxicity. Audiometry shows cisplatin-induced ototoxicity in 75 to 100% of patients, which may be associated with tinnitus and hearing loss. Ototoxicity is rare with conventional dose carboplatin therapy. Monitoring hearing with audiograms may identify early signs before significant impairment occurs. Cisplatin causes mild haematological toxicity to all 3 blood lineages. Haematological toxicity is dose-limiting for carboplatin, with thrombocytopenia being a greater problem than leucopenia. Although carboplatin is not toxic to the kidney, renal function markedly affects the severity of carboplatin-induced thrombocytopenia. The major clearance mechanism of cisplatin is irreversible binding in plasma and tissues, while carboplatin is cleared by glomerular filtration. Metabolism of cisplatin to aqua, amino acid and protein species is extensive, whereas carboplatin exists mainly as the free unchanged form. Strong relationships between carboplatin renal clearance, glomerular filtration rate, area under the plasma concentration-time curve (AUC) of filterable platinum and severity of thrombocytopenia have prompted dose adjustment according to renal function. New analogues such as JM216 offer the potential advantages of oral administration and few nonhaematological toxicities. Analogues based on the diaminocyclohexane ligand have encountered problematic neurotoxicity.

show abstract

“…Also, no increase in excretion of tubular enzymes could be observed, indicating that tubular function remained intact during and after JM216 treatment. Animal studies have shown no nephrotoxicity of JM216, as assessed by inulin clearance in mice [15] or by creatinine clearance in rats [14]. Only after chronic daily dosing of JM216 is a slight decrease in GFR observed in mice [15].…”

Section: Discussionmentioning

confidence: 99%