{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:08:15Z","timestamp":1777914495789,"version":"3.51.4"},"reference-count":28,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[1993,9,1]],"date-time":"1993-09-01T00:00:00Z","timestamp":746841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[1993,9]]},"abstract":"<jats:p>Renal papillary cytoplasmic granularity (RPCG) induced by carbonic anhydrase inhibitors (CAIs) in rats is characterized by the accumulation of dense secondary lysosomes in epithelial, endothelial, and interstitial cells and may be related to drug-induced potassium depletion. Female Sprague-Dawley rats were given the CAI, acetazolamide, by gavage. Half were supplemented with 1% potassium chloride in the drinking water. Two treated groups were allowed to recover for 1 or 2 mo. Potassium supplementation inhibited RPCG by 80% but produced little amelioration of the mild 13% decrease in serum potassium induced by 200 mg\/kg\/ day acetazolamide for 28 days. Acetazolamide-induced RPCG is reversible because 1- and 2-mo recovery periods decreased the incidence by 75% and 80%, respectively. The results support the hypothesis that RPCG is related to potassium depletion secondary to carbonic anhydrase inhibition. Because supplementation of potassium chloride had little effect on serum potassium, these data suggest that depletion of renal medullary potassium content is important in the pathogenesis of RPCG as previously suggested by others. Other types of diuretics that produce hypokalemia as a side effect may not deplete medullary potassium since RPCG has not been reported in humans or animals given these drugs.<\/jats:p>","DOI":"10.1177\/019262339302100504","type":"journal-article","created":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T19:26:22Z","timestamp":1257535582000},"page":"449-455","source":"Crossref","is-referenced-by-count":9,"title":["Renal Papillary Cytoplasmic Granularity and Potassium Depletion Induced by Carbonic Anhydrase Inhibitors in Rats"],"prefix":"10.1177","volume":"21","author":[{"given":"Roger A.","family":"Owen","sequence":"first","affiliation":[{"name":"Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genevi\u00e8ve","family":"Durand-Cavagna","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain","family":"Molon-Noblot","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Boussiquet-Leroux","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Berry","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France, Shell Research Limited, Sittingbourne Research Center, Sittingbourne, Kent ME9 8AG, England"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Tonkonoh","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, 2 Biometrics Research Department"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chennekatu P.","family":"Peter","sequence":"additional","affiliation":[{"name":"Department of Safety Assessment, West Point, Pennsylvania 19486, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea R.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Safety Assessment, West Point, Pennsylvania 19486, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[1993,9,1]]},"reference":[{"key":"atypb1","first-page":"107","volume":"36","author":"Aithal HN","year":"1977","journal-title":"Lab. 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