Phenacetin-induced Renal Disease in Rats

Fordham, Christopher C.; Huffines, William D.; Welt, Louis G.

doi:10.7326/0003-4819-62-4-738

Cited by 48 publications

(8 citation statements)

References 10 publications

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“…These effects of hydration in diminishing the renal gradient for APAP suggest that dehydration as well as the amount of analgesic compound consumed may have a bearing on the development of the renal lesions. It might offer a possible explanation for the failure to produce papillary necrosis in the majority of animals given large doses of phenacetin for long periods of time (4)(5)(6) if no effort were made to limit fluid intake. This contention is supported by the preliminary results of studies performed by Kincaid-Smith, Saker, McKenzie, and Muriden in the rat (23).…”

Section: Resultsmentioning

confidence: 99%

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Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse

Bluemle¹,

Goldberg²

1968

J. Clin. Invest.

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A B S T R A C T Since either aspirin or phenacetin might be causative in the nephropathy of analgesic abuse, studies were designed to examine the renal accumulation and distribution of the major metabolic products of these compounds, salicylate and N-acetyl-p-aminophenol (APAP) respectively, in dogs. Nineteen hydropenic animals were studied, of which seven were given phenacetin, nine received acetyl salicylic acid, two were given both aspirin and phenacetin, and one received APAP directly. Two of three hydrated animals were given phenacetin and one was given aspirin. During peak blood levels of salicylate and (or) APAP, the kidneys were rapidly removed, frozen, sliced from cortex to papillary tip, and analyzed for water, urea, APAP, and salicylate.No renal medullary gradient for salicylate was demonstrable during both hydropenic and hydrated states. In contrast, both free and conjugated APAP concentrations rose sharply in the inner medulla during hydropenia, reaching a mean maximal value at the papillary tip exceeding 10 times the cortical concentration (P < 0.001), a distribution similar to that of urea. Salicylate had no effect on the APAP gradient, but hydration markedly reduced both the APAP and urea gradients in the medulla. The data indicate that APAP

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Section: Resultsmentioning

confidence: 99%

“…Hydropenia was induced by water deprivation for 18-X24 hr. 5 units of pitressin tannate in oil was given 16 hr before each experiment. Control urine samples for use as blanks were obtained by direct bladder puncture.…”

Section: Methodsmentioning

confidence: 99%

Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse

Bluemle¹,

Goldberg²

1968

J. Clin. Invest.

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“…They suggested that these effects were related more to the ingestion of phenacetin than to age or concomitant dosage with acetylsalicylic acid. The possibility that phenacetin can induce formation of plaques and neurofibrillary tangles was therefore investigated by giving rats doses of phenacetin equivalent to approximately 2 or 30 times the dose reported to produce kidney damage (Fordham, Huffines and Welt, 1964) and possibly brain damage (Murray et al, 1971) in man.…”

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confidence: 99%

Some effects of phenacetin on the rat

Yates

Wilson

1976

The Journal of Pathology

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“…Three out of 25 rabbits fed phenacetin developed renal papillary necrosis. Using very large doses of phenacetin, Fordham et al (1965) induced papillary necrosis in 3 out of 39 rats over a period of 4 weeks. Nanra et al ( 1971) obtained similar results and, by subjecting the rats to daily dehydration, a higher incidence of papillary necrosis (37.5 per cent over 8-20 weeks) was induced.…”

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Urothelial Changes of the Renal Papillae in Sprague‐dawley Rats Induced by Long Term Feeding of Phenacetin

Johansson

Angervall

1976

Acta Pathologica Microbiologica Scandinavica Section A Patholog

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Johansson, S. & Angervall, L. Urothelial changes of the renal papillae in Sprague-Dawley rats induced by long term feeding of phenacetin. Acta path. microbiol. scand. Sect. A, 84: [375][376][377][378][379][380][381][382][383] 1976.Thirty female Sprague-Dawley rats were fed 0.535 per cent phenacetin in the diet for up to 110 weeks. Twenty-six of these rats developed urothelial hyperplasia, partly papillary, of the renal papillae. Twenty-eight rats showed dilatation of the vasa recta frequently associated with thrombus formation and calcification. One phenacetin fed rat had epithelial hyperplasia associated with chronic pyelitis. I n 2 of the 30 control rats urothelial hyperplasia was found to be associated with chronic pyelitis. The hyperplastic urothelial changes and vascular changes were often, but not always, present simultaneously. One control rat developed a mammary carcinoma, as compared with 5 rats in the phenacetin group. Four phenacetin fed rats developed carcinoma of the ear duct. The results of the present investigation provide evidence that phenacetin can induce proliferative lesions of the urothelium of the rat renal pelvis with weak carcinogenic activity in the ear duct and mammary glands.

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Phenacetin-induced Renal Disease in Rats

Cited by 48 publications

References 10 publications

Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse

Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse

Some effects of phenacetin on the rat

Urothelial Changes of the Renal Papillae in Sprague‐dawley Rats Induced by Long Term Feeding of Phenacetin

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