{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:14:00Z","timestamp":1745554440631,"version":"3.40.4"},"reference-count":1,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron"],"published-print":{"date-parts":[[2000]]},"abstract":"<jats:p>&lt;i&gt;Background\/Aims:&lt;\/i&gt; Several recent studies have suggested that angiotensin-converting enzyme (ACE) inhibitors ameliorate chronic cyclosporin A (CyA) tubulo-interstitial disease by mechanisms independent of their antihypertensive effects. The aim of the present study was to determine whether ACE inhibition exerts a direct beneficial effect on the tubulo-interstitium in an in vitro model of chronic CyA nephropathy. &lt;i&gt;Methods:&lt;\/i&gt; Primary cultures of human proximal tubular cells (PTC) and renal cortical fibroblasts (CF) were exposed for 24 h to CyA in the presence or absence of enalaprilat. Parameters of tubulo-interstitial nephrotoxicity were then measured including collagen synthesis (proline incorporation), tubular viability and function (thymidine incorporation, lactate dehydrogenase release, and apical sodium-hydrogen exchange), and secretion of insulin-like growth factor I, transforming growth factor beta 1 (TGF\u03b2&lt;sub&gt;1&lt;\/sub&gt;), and platelet-derived growth factor. &lt;i&gt;Results:&lt;\/i&gt; CyA promoted CF collagen synthesis, PTC cytotoxicity (suppressed viability, growth and sodium transport), and tubulo-interstitial fibrogenic cytokine release (CF secretion of insulin-like growth factor I and PTC secretion of TGF\u03b2&lt;sub&gt;1&lt;\/sub&gt; and platelet-derived growth factor). Enalaprilat completely reversed the stimulatory effects of CyA on CF collagen synthesis (CyA + enalaprilat 6.40 \u00b1 0.50% vs. CyA alone 8.33 \u00b1 0.56% vs. control 6.57 \u00b1 0.62% vs. enalaprilat alone 5.55 \u00b1 0.93%, p &lt; 0.05) and PTC secretion of TGF\u03b2&lt;sub&gt;1&lt;\/sub&gt; (0.71 \u00b1 0.11, 1.13 \u00b1 0.09, 0.89 \u00b1 0.07, and 0.67 \u00b1 0.09 ng\/mg protein\/day, respectively, p &lt; 0.05). However, the other manifestations of CyA toxicity were not significantly reversed by concomitant enalaprilat administration. &lt;i&gt;Conclusions:&lt;\/i&gt; ACE inhibition directly prevents CyA-induced interstitial fibrosis, but not proximal tubule cytotoxicity, independently of haemodynamic and systemic renin-angiotensin system effects. Renoprotection may be partially afforded by directly preventing the tubular secretion of TGF\u03b2&lt;sub&gt;1&lt;\/sub&gt;.<\/jats:p>","DOI":"10.1159\/000045837","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T13:07:10Z","timestamp":1050412030000},"page":"473-481","source":"Crossref","is-referenced-by-count":14,"title":["Enalaprilat Directly Ameliorates in vitro Cyclosporin Nephrotoxicity in Human Tubulo-Interstitial Cells"],"prefix":"10.1159","volume":"86","author":[{"given":"David W.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather J.","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Vesey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weier","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Field","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A.","family":"Pollock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2000,12,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1159\/000020626"}],"container-title":["Nephron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/45837","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/45837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:48:08Z","timestamp":1745470088000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000045837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000]]},"references-count":1,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2000,12,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000045837","archive":["Portico"],"relation":{},"ISSN":["1660-8151","2235-3186"],"issn-type":[{"type":"print","value":"1660-8151"},{"type":"electronic","value":"2235-3186"}],"subject":[],"published":{"date-parts":[[2000]]}}}