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The renal response of a nonhuman primate (baboon) to certain nonsteroidal anti-inflammatory drugs (NSAIDs).

Skelton-Stroud, Paul Nicholas. (1987) The renal response of a nonhuman primate (baboon) to certain nonsteroidal anti-inflammatory drugs (NSAIDs). Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

Renal papillary necrosis (RPN) in man can follow abuse of non-narcotic analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs). Secondary cortical interstitial nephritis may also occur. Affected kidneys can progress to end-stage renal failure or urothelial carcinoma. This study reports kidney lesions following administration of two oxicam NSAIDs, piroxicam (Feldene, Pfizer) and CGP 13 214D to a nonrodent species (baboon) as required by regulatory authorities for predictive toxicology. Naturally-occurring kidney lesions were surveyed in 217 pairs of kidneys to provide data for comparison with treatment-related lesions. The ten most common changes comprised lymphocytic infiltrates (63%), multinucleate tubule cells (53%), altered glomeruli (46%), mineralisation (27%), urothelial inclusions (28%), urothelial vacuoles (20%), ectopic nephrons (16%), pyelitis (15%), tubular basophilia (11%) and tubulointerstitial nephritis (9%). Treatment-related lesions included unilateral RPN in single animals at 20 mg/ml and 6 mg/ml piroxicam, accompanied variously by epithelial hyperplasia, interstitial necrosis, haemorrhage, oedema and mineralisation. Calcium oxalate crystals were identified by histochemistry, scanning electronmicroscopy and X-ray diffraction methods. Similar changes without RPN were found with CGP 13 214D. Only urinalysis showed some indication of kidney damage during the study. Data were compared with similar experimentally-induced NSAID lesions in other animals including man. Significant differences were noted. In this study RPN was focal, discrete, unilateral and less severe than reported in man. No consistent cortical changes occurred. Crystals have not been reported in man, but were seen in this study. NSAID anti-prostaglandin activity is considered responsible for the kidney changes. Continued investigation into species variation of RPN, the regenerative capacity of medulla interstitial cells and improved non-invasive detection of renal function should contribute significantly to improved drug design for human clinical treatment.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
NameEmailORCID
Skelton-Stroud, Paul Nicholas.
Date : 1987
Contributors :
ContributionNameEmailORCID
http://www.loc.gov/loc.terms/relators/THS
Additional Information : Thesis (M.Phil.)--University of Surrey (United Kingdom), 1987.
Depositing User : EPrints Services
Date Deposited : 22 Jun 2018 14:26
Last Modified : 06 Nov 2018 16:53
URI: http://epubs.surrey.ac.uk/id/eprint/848066

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