p38-MAPK inhibition and endotoxin induced tubular dysfunction in men

被引:5
|
作者
Zijlstra, JG
Tulleken, JE
Ligtenberg, JJM
de Boer, P
van der Werf, TS
机构
[1] Univ Groningen Hosp, Dept Internal Med, Intens & Resp Care Unit, NL-9700 RB Groningen, Netherlands
[2] RW Johnson Pharmaceut Res Inst, Bassersdorf, Switzerland
来源
JOURNAL OF ENDOTOXIN RESEARCH | 2004年 / 10卷 / 06期
关键词
endotoxin; renal failure; p38-MAPK inhibition; tubulopathy;
D O I
10.1179/096805104225005869
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: To evaluate the possibility of preventing endotoxin induced renal damage by p38-MAPK inhibition in a human model. Design and Methods: Twenty-one healthy young male volunteers received 4 ng/kg Escherichia coli endotoxin as a single dose. Four groups of volunteers received an oral dose of placebo or 350, 700 or 1400 mg RWJ-67657, a p38-MAPK inhibitor, 20 min before endotoxin infusion. Urine samples were collected at set time intervals. The urinary excretion rate of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase, as indicators of tubular dysfunction was determined. Results: There was a significant increase of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase urine excretion rate after endotoxin infusion in the placebo group. p38-MAPK inhibition prevented the increase of markers for tubulopathy. Conclusions: Endotoxin infusion induces measurable tubular damage. Blocking the p38- MAPK may prevent this damage. The mechanism is unclear, but blocking TNF-alpha release is a possible explanation.
引用
收藏
页码:402 / 405
页数:4
相关论文
共 50 条
  • [1] Effect of p38-MAPK inhibition on sepsis-induced myocardial dysfunction
    Loken, L
    Brahmbhatt, S
    Sharma, AC
    SHOCK, 2005, 23 : 82 - 82
  • [2] Topical p38-MAPK inhibition attenuates burn wound induced cardiac dysfunction
    Hoesel, L.
    Mattar, A.
    Arbabi, S.
    Niederbichler, A.
    Westfall, M.
    Wang, S.
    Hemmila, M.
    SHOCK, 2007, 27 : 82 - 82
  • [3] Specific inhibition of p38-MAPK signaling suppresses experimental arthritis and inflammation induced hypoxia
    Guenthoer, P.
    Fuchs, K.
    Lamparter, D.
    Reischl, G.
    Aidone, S.
    Koenig, M.
    Laufer, S.
    Roecken, M.
    Pichler, B. J.
    Kneilling, M.
    EXPERIMENTAL DERMATOLOGY, 2014, 23 (03) : E29 - E29
  • [4] Inhibition of p38-MAPK alters SRC coactivation and estrogen receptor phosphorylation
    Antoon, James W.
    Bratton, Melyssa R.
    Guillot, Lori M.
    Wadsworth, Scott
    Salvo, Virgilio A.
    Burow, Matthew E.
    CANCER BIOLOGY & THERAPY, 2012, 13 (11) : 1026 - 1033
  • [5] Inflame my heart (by p38-MAPK)
    Clerk, Angela
    Sugden, Peter H.
    CIRCULATION RESEARCH, 2006, 99 (05) : 455 - 458
  • [6] Mechanisms of MAPK kinase-independent p38-MAPK activation
    Bassi, Rekha
    Heads, Richard
    Marber, Michael
    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2008, 44 (04) : 770 - 771
  • [7] A novel cardioprotective p38-MAPK/mTOR pathway
    Hernandez, Gonzalo
    Lal, Hind
    Fidalgo, Miguel
    Guerrero, Ana
    Zalvide, Juan
    Force, Thomas
    Pombo, Celia M.
    EXPERIMENTAL CELL RESEARCH, 2011, 317 (20) : 2938 - 2949
  • [8] Myrtenol Reduces Orofacial Nociception and Inflammation in Mice Through p38-MAPK and Cytokine Inhibition
    Oliveira, Janaine P.
    Abreu, Fabiula F.
    Bispo, Jose Marcos M.
    Cerqueira, Anderson R. A.
    dos Santos, Jose Ronaldo
    Correa, Cristiane B. B.
    Costa, Soraia K. P.
    Camargo, Enilton A. A.
    FRONTIERS IN PHARMACOLOGY, 2022, 13
  • [9] HIV-1 gp120-induced tubular epithelial cell apoptosis is mediated through p38-MAPK phosphorylation
    Kapasi, AA
    Patel, G
    Franki, N
    Singhal, PC
    MOLECULAR MEDICINE, 2002, 8 (11) : 676 - 685
  • [10] HIV-1 gp120-Induced Tubular Epithelial Cell Apoptosis Is Mediated Through p38-MAPK Phosphorylation
    Aditi A. Kapasi
    Geeta Patel
    Nicholas Franki
    Pravin C. Singhal
    Molecular Medicine, 2002, 8 : 676 - 685