{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:17:54Z","timestamp":1767212274316},"reference-count":21,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:p> This study sought to determine whether gentamicin, a mainstay in treating Gram-negative sepsis, alters endotoxin (lipopolysaccharide; LPS)-driven TNF-\u03b1 increases. CD-1 mice received 1 day of gentamicin treatment. Either 0, 24, or 72 h later, gentamicin-treated and control mice were injected with LPS. Renal cortical and plasma TNF-\u03b1, as well as MCP-1, protein levels were measured 2 or 24 h post-LPS injection. Renal cortical mRNAs for TNF-\u03b1, MCP-1, IL-10, and inducible nitric oxide synthase (iNOS) were also determined. Finally, gentamicin's potential impact(s) on TNF-\u03b1\/MCP-1 mRNA levels in nontraditional \u201ctarget\u201d organs (liver, spleen) was assessed. Gentamicin, when administered alone, slightly increased renal cortical TNF-\u03b1 and MCP-1 mRNAs, but without changing plasma or renal TNF-\u03b1\/MCP-1 protein levels. The gentamicin protocol induced no overt renal damage (assessed by blood urea nitrogen, creatinine, and histology). Nevertheless, gentamicin augmented LPS responsiveness, as manifested, in part, by a doubling of LPS-induced plasma TNF-\u03b1 increases (vs. LPS injection alone). Plasma and renal cortical MCP-1 protein levels were also selectively enhanced. Gentamicin augmented LPS-driven renal mRNA increases (TNF-\u03b1, MCP-1, IL-10, iNOS). However, this was not an entirely renal-specific response, since gentamicin also enhanced basal and LPS-stimulated hepatic TNF-\u03b1 mRNA levels. Subclinical gentamicin toxicity can potentiate LPS-driven TNF-\u03b1 increases. Alterations in multiple proinflammatory (TNF-\u03b1; MCP-1; iNOS) and anti-inflammatory (IL-10) genes in the kidney, and possibly in extrarenal organs, may be involved. Thus gentamicin's activity in Gram-negative sepsis may extend beyond its traditional antimicrobial effect. <\/jats:p>","DOI":"10.1152\/ajprenal.00144.2007","type":"journal-article","created":{"date-parts":[[2007,4,19]],"date-time":"2007-04-19T00:38:47Z","timestamp":1176943127000},"page":"F43-F49","source":"Crossref","is-referenced-by-count":8,"title":["\u201cSubclinical\u201d gentamicin nephrotoxicity: a potential risk factor for exaggerated endotoxin-driven TNF-\u03b1 production"],"prefix":"10.1152","volume":"293","author":[{"given":"Richard A.","family":"Zager","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2006.10.015"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1988.255.2.F265"},{"key":"R3","unstructured":"Chambers HF. Aminoglycosides. In: Goodman and Gilman's Pharmacologic Basis of Therapeutics (11th ed.), edited by Brunton LL, Lazo JS, and Parker KL. New York: McGraw-Hill, 2006, chapt. 45, p. 1159."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004090740"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(98)00058-8"},{"key":"R6","unstructured":"Hammond TG, Majewski RR, Kaysen JH, Goda FO, Navar GL, Pontillon F, Verroust PJ. Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin. Am J Physiol Renal Physiol 272: F117\u2013F123, 1997."},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000130340.93930.DD"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Loef BG, Epema AH, Smilde TD, Henning RH, Ebels T, Navis G, Stegeman CA. Immediate postoperative renal function deterioration in cardiac surgical patients predicts in hospital mortality, and long-term survival. 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Circ Res 80: 20\u201328, 1992.","DOI":"10.1161\/01.RES.70.1.20"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00023.2005"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002092"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00011.2006"},{"key":"R19","unstructured":"Zager RA, Johnson AC, Lund S, Randolph-Habecker J. Toll-like receptor (TLR4) shedding, and depletion: acute proximal tubular cell responses to hypoxic injury. Am J Physiol Renal Physiol 292: F304\u2013F312, 2007."},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112552"},{"key":"R21","unstructured":"Zager RA, Sharma HM. Gentamicin increases renal susceptibility to an acute ischemic insult. J Lab Clin Med 101: 670\u2013678, 1983."}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00144.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T22:35:29Z","timestamp":1567982129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00144.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,7]]}},"alternative-id":["10.1152\/ajprenal.00144.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00144.2007","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,7]]}}}