{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:49:43Z","timestamp":1768474183220,"version":"3.49.0"},"reference-count":13,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemotherapy"],"published-print":{"date-parts":[[2002]]},"abstract":"<i>Background:<\/i> Nitric oxide (NO) has been shown to play a role in maintaining normal renal function. However, the role of NO in cisplatin (CDDP)-induced nephrotoxicity is still unclear. The aim of the present work was to examine the effect of the NO synthase (NOS) inhibitor, 2-amino-4-methylpyridine, on the severity of CDDP-induced nephrotoxicity. <i>Methods:<\/i> Male Wistar rats were divided into six groups. Three control groups received plain drinking water or water containing 1.5% <i>L<\/i>-arginine. One of the two groups receiving plain water was treated with an intraperitoneal injection of 2-amino-4-methylpyridine (1 mg\/kg in normal saline), and the other two control groups were injected intraperitoneally with normal saline. Another three groups were treated in the same manner and injected with CDDP (6 mg\/kg, i.p.). CDDP was injected 1 h after 2-amino-4-methylpyridine treatment. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analysed. <i>Results:<\/i> CDDP-treated rats showed increases in the kidney weight as a percentage of the total body weight and serum creatinine and urea levels and decreases in serum albumin and calcium levels. Also, CDDP treatment induced reductions in the kidney total nitrate\/nitrite (NO<sub>x<\/sub>), reduced glutathione (GSH) and glutathione peroxidase activity (GSH-Px) levels and an increase in the kidney malondialdehyde (MDA) production level. In contrast, 2-amino-4-methylpyridine treatment 1\u00a0h prior to CDDP injection induced marked exacerbation of CDDP-induced nephrotoxicity, as manifested by severe aggravation of the indices of nephrotoxicity. Also, 2-amino-4-methylpyridine plus CDDP-treated rats showed exaggeration of the reduction in the kidney total NO<sub>x<\/sub> content and GSH-Px activity and elevation of the kidney platinum accumulation level with normalization of the kidney MDA production level and rebound in the kidney GSH content. Histopathologically, CDDP-treated rats showed marked interstitial nephritis, tubular atrophy and tubular necrosis. However, treatment with 2-amino-4-methylpyridine 1 h prior to CDDP injection revealed marked exacerbation of CDDP-induced histopathological changes. <i>Conclusions:<\/i> The present findings suggest that NO plays a role in CDDP-induced nephrotoxicity. Administration of 2-amino-4-methylpyridine, an NOS inhibitor, exacerbates CDDP-induced nephrotoxicity.<\/jats:p>","DOI":"10.1159\/000069714","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T21:05:40Z","timestamp":1050440740000},"page":"309-315","source":"Crossref","is-referenced-by-count":46,"title":["Inhibition of Nitric Oxide Synthase Aggravates Cisplatin-Induced Nephrotoxicity: Effect of 2-Amino-4-Methylpyridine"],"prefix":"10.1159","volume":"48","author":[{"given":"Sherif Y.","family":"Saad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawfeeg A.O.","family":"Najjar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed H.","family":"Daba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ammar C.","family":"Al-Rikabi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2003,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90192-Y"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-100101947"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.32.1.449"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-2042.1999.00058.x"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90269-0"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(71)90289-0"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2000.0319"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.36.21035"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.2001.02303.x"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.2000.0764"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)02075-6"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200108270-00009"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00161.x"}],"container-title":["Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/69714","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/69714","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:46:56Z","timestamp":1745466416000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000069714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002]]},"references-count":13,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2003,4,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000069714","archive":["Portico"],"relation":{},"ISSN":["0009-3157","1421-9794"],"issn-type":[{"value":"0009-3157","type":"print"},{"value":"1421-9794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002]]}}}