Comparative Nephrotoxicity of Aspirin and Phenacetin Derivatives

Calder, I. C.; Funder, C. C.; Green, C. R.; Ham, Kathryn N.; Tange, J. D.

doi:10.1136/bmj.4.5786.518

Cited by 116 publications

(22 citation statements)

References 9 publications

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“…These findings are in agreement with those reported previously by others (Green et al 1969;Calder et al 1971;Kiese et al 1975;Davis et al 1983;Newton et al 1983;Gartland et al 1989). We have now shown that the nephrotoxicity due to PAP can be prevented by co-administration of ascorbic acid (Table 2, Fig.…”

Section: Discussionsupporting

confidence: 95%

“…It is also used in photographic processing and along with other aminophenols as hair dyes (Anon 1988). PAP is acutely nephrotoxic, producing necrosis to the pars recta of the proximal tubule in the rat following a single dose (Green et al 1969;Calder et al 1971;Kiese et al 1975;Davis et al 1983;Newton et al 1983;Gartland et al 1989). Associated with these morphological findings are dose-related alterations in renal function and a consequent elevation in blood urea nitrogen.…”

Section: Introductionmentioning

confidence: 91%

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Effect of ascorbic acid, acivicin and probenecid on the nephrotoxicity of 4-aminophenol in the Fischer 344 rat

1993

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4-Aminophenol (p-aminophenol, PAP) causes selective necrosis to the pars recta of the proximal tubule in Fischer 344 rats. The basis for this selective toxicity is not known but PAP can undergo oxidation in a variety of systems to form the 4-aminophenoxy free radical. Oxidation or disproportionation of this radical will form 1,4-benzoquinoneimine which can covalently bind to cellular macromolecules. We have recently reported that a glutathione conjugate of PAP, 4-amino-3-S-glutathionylphenol, is more toxic to the kidney than the parent compound itself. In this study we have examined the distribution and covalent binding of radiolabel from 4-[ring 3H]-aminophenol in the plasma, kidney and liver of rats 24 h after dosing and related these findings to the extent of nephrotoxicity. In addition, we have examined the effect of ascorbic acid which will slow the oxidation of PAP; acivicin, an inhibitor of gamma-glutamyltransferase and hence the processing of glutathione-derived conjugates; and probenecid, an inhibitor of organic anion transport on the nephrotoxicity produced by PAP. Administration of a single dose of PAP at 458 or 687 mumol kg-1 produced a dose-related alteration in renal function within 24 h which was associated with proximal tubular necrosis. The lesion at the lower dose was restricted to the S3 proximal tubules in the medullary rays, while at the higher dose it additionally affected the S3 tubules in the pars recta region of the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 95%

Section: Introductionmentioning

confidence: 91%

Effect of ascorbic acid, acivicin and probenecid on the nephrotoxicity of 4-aminophenol in the Fischer 344 rat

1993

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“…There are some animal studies that show 5-ASA-induced IN to be a dose-related papillary necrosis of the kidney [14]. In addition, 5-ASA has structural similarities to both phenacetin and aspirin, which are known to cause analgesic nephropathy with papillary necrosis.…”

Section: Discussionmentioning

confidence: 98%

Acute Tubular Injury Associated with Mesalazine Therapy in an Adolescent Girl with Inflammatory Bowel Disease

et al. 2007

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Mesalazine is a first-line drug in pediatric inflammatory bowel disease, and is effective as primary treatment and maintenance therapy. It's usually well tolerated, but various side effects have been described. A 15-year-old female with ulcerative colitis developed polyuria, polydipsia, vomiting, and fatigue. She was receiving mesalazine (500 mg, thrice daily, p.o.) and prednisolone for 4 months. She was detected as acute tubular injury as she had dehydration, acidosis, hypostenuria, hematuria, proteinuria, low levels of potassium, uric acid and bicarbonate. These findings were attributed to interstitial nephritis as a side effect of mesalazine, however as renal biopsy was disapproved by the parents, it was not confirmed. After discontinuation of mesalazine her renal tubular functions improved. Potassium and phosphorus supplements were stopped after 7 months, although she had to continue bicarbonate supplementation. We conclude that regular renal screening is important in patients receiving 5-ASA therapy to prevent rare but serious complications, such as interstitial nephritis sometimes leading to chronic renal failure.

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“…Jollow et al (7) and Davis et al (8) used intraperitoneal and oral routes respectively for the administration of paracetamol to rats, whereas we have used tail vein injection to determine the toxicity of single doses of drugs related to paracetamol (29). The methods we used for metabolite analysis were sufficiently precise to detect differences in metabolite profiles following the administration of a non-toxic dose of paracetamol (2 mmole/kg) by the three different routes.…”

Section: Discussionmentioning

confidence: 99%

The metabolism and toxicity of paracetamol in Sprague-Dawley and wistar rats

Hart

Calder

Tange

1982

European Journal of Drug Metabolism and Pharmacokinetics

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Urinary paracetamol metabolites from Sprague-Dawley and Wistar rats were analysed by reversed-phase HPLC. Variations in the metabolic profile were observed as a function of dose, age, sex, species and route of administration. In addition the effect of 3-methylcholanthrene as an inducer of cytochrome P450 mixed function oxidase on paracetamol metabolism was also studied. Increased oxidative metabolism which lead to the formation of 3-thiomethylparacetamol conjugates along with paracetamol mercapturic acid could be correlated with increased susceptibility to hepatic damage. Furthermore it appears that the length of time taken for excretion and the level of free drug excreted may be involved in the aetiology of chronic renal damage.

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Comparative Nephrotoxicity of Aspirin and Phenacetin Derivatives

Cited by 116 publications

References 9 publications

Effect of ascorbic acid, acivicin and probenecid on the nephrotoxicity of 4-aminophenol in the Fischer 344 rat

Effect of ascorbic acid, acivicin and probenecid on the nephrotoxicity of 4-aminophenol in the Fischer 344 rat

Acute Tubular Injury Associated with Mesalazine Therapy in an Adolescent Girl with Inflammatory Bowel Disease

The metabolism and toxicity of paracetamol in Sprague-Dawley and wistar rats

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