Aprotinin but not tranexamic acid inhibits cytokine-induced inducible nitric oxide synthase expression

Gary E. Hill, Richard A. Robbins

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Cell expression of inducible nitric oxide synthase (iNOS) is increased by cytokines, which results in high endogenous concentrations of nitric oxide (NO) and has been implicated in organ injury, including myocardial reperfusion injury. Serine protease inhibitors reduce cytokine-induced iNOS expression. The protease inhibitors aprotinin and tranexamic acid, which are used to reduce blood loss after cardiac surgery, were evaluated in vitro on cytokine-induced iNOS expression and the resulting NO production to demonstrate the relative antiinflammatory effects of each drug. A murine bronchial epithelial cell line (LA-4) was stimulated with cytomix (tumor necrosis factor α, interleukin 1β, and γ-interferon) with or without aprotinin, tranexamic acid, or N-α-tosyl-L-lysine chloromethyl ketone (TLCK; a protease inhibitor). The resultant iNOS expression was measured by using Northern blot analysis and cell supernatant nitrite concentrations (in aqueous media, NO is oxidized primarily to nitrite, NO2) by chemiluminescence. Nitrite concentrations in the supernatant were significantly increased by cytomix, not affected by any concentration of tranexamic acid, but significantly (P < 0.05) reduced by aprotinin and TLCK. Consistent with the nitrite reduction, aprotinin significantly (P < 0.05) reduced cytokine-induced iNOS expression, while tranexamic acid had no effect. Aprotinin but not tranexamic acid reduces endogenous cytokine- induced NO production by inhibiting iNOS expression. Since increased endogenous NO concentrations secondary to iNOS activation have been implicated in organ injury, aprotinin may have clinical benefits when compared with tranexamic acid.

Original languageEnglish (US)
Pages (from-to)1198-1202
Number of pages5
JournalAnesthesia and Analgesia
Volume84
Issue number6
DOIs
StatePublished - 1997

Fingerprint

Tranexamic Acid
Aprotinin
Nitric Oxide Synthase Type II
Cytokines
Nitrites
Nitric Oxide
Tosyllysine Chloromethyl Ketone
Protease Inhibitors
Myocardial Reperfusion Injury
Serine Proteinase Inhibitors
Wounds and Injuries
Luminescence
Interleukin-1
Northern Blotting
Interferons
Thoracic Surgery
Lysine
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Epithelial Cells

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Aprotinin but not tranexamic acid inhibits cytokine-induced inducible nitric oxide synthase expression. / Hill, Gary E.; Robbins, Richard A.

In: Anesthesia and Analgesia, Vol. 84, No. 6, 1997, p. 1198-1202.

Research output: Contribution to journalArticle

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