Document Detail


Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom.
MedLine Citation:
PMID:  15448874     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor necrosis factor-alpha (TNF-alpha), we determined the effect of these drugs on the renal damage induced by supernatants of macrophages activated with Crotalus durissus cascavella venom in order to identify the role of TNF-alpha in the process. Rat peritoneal macrophages were collected with RPMI medium and stimulated in vitro with C.d. cascavella venom (10 micro g/ml) in the absence and presence of thalidomide (15 micro M) or pentoxifylline (500 micro M) for 1 h and washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated perfused rat kidney (N = 6 for each group). The first 30 min of each experiment were used as control. The supernatant was added to the perfusion system. All experiments lasted 120 min. The toxic effect of the preparation of venom-stimulated macrophages on renal parameters was determined. At 120 min, thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase in perfusion pressure caused by the venom (control = 114.0 +/- 1.3; venom = 137.1 +/- 1.5; Thalid = 121.0 +/- 2.5; Ptx = 121.4 +/- 4.0 mmHg), renal vascular resistance (control = 4.5 +/- 0.2; venom = 7.3 +/- 0.6; Thalid = 4.5 +/- 0.9; Ptx = 4.8 +/- 0.6 mmHg/ml g-1 min-1), urinary flow (control = 0.23 +/- 0.001; venom = 0.44 +/- 0.01; Thalid = 0.22 +/- 0.007; Ptx = 0.21 +/- 0.009 ml g-1 min-1), glomerular filtration rate (control = 0.72 +/- 0.06; venom = 1.91 +/- 0.11; Thalid = 0.75 +/- 0.04; Ptx = 0.77 +/- 0.05 ml g-1 min-1) and the decrease in percent tubular sodium transport (control = 77.0 +/- 0.9; venom = 73.9 +/- 0.66; Thalid = 76.6 +/- 1.1; Ptx = 81.8 +/- 2.0%), percent tubular chloride transport (control = 77.1 +/- 1.2; venom = 71.4 +/- 1.1; Thalid = 77.6 +/- 1.7; Ptx = 76.8 +/- 1.2%), and percent tubular potassium transport (control = 72.7 +/- 1.1; venom = 63.0 +/- 1.1; Thalid = 72.6 +/- 1.0; Ptx = 74.8 +/- 1.0%), 30 min before and during the stimulation of macrophages with C.d. cascavella venom. These data suggest the participation of TNF-alpha in the renal effects induced by supernatant of macrophages activated with C.d. cascavella venom.
Authors:
A M C Martins; A C L Nobre; A C Almeida; G Bezerra; A A M Lima; M C Fonteles; H S A Monteiro
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Publication Detail:
Type:  Journal Article     Date:  2004-09-22
Journal Detail:
Title:  Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]     Volume:  37     ISSN:  0100-879X     ISO Abbreviation:  Braz. J. Med. Biol. Res.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-27     Completed Date:  2005-04-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112917     Medline TA:  Braz J Med Biol Res     Country:  Brazil    
Other Details:
Languages:  eng     Pagination:  1525-30     Citation Subset:  IM    
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Instituto de Biomedicina e Unidade de Pesquisas Clínicas, Universidade Federal do Ceará, 60420-970 Fortaleza, Ceará, Brazil. martinsalice@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Crotalid Venoms / antagonists & inhibitors,  toxicity*
Female
Immunosuppressive Agents / pharmacology*
Kidney / drug effects*
Macrophage Activation / drug effects
Macrophages, Peritoneal / drug effects*,  metabolism
Male
Pentoxifylline / pharmacology*
Rats
Rats, Wistar
Thalidomide / pharmacology*
Tumor Necrosis Factor-alpha / drug effects,  metabolism*
Chemical
Reg. No./Substance:
0/Crotalid Venoms; 0/Immunosuppressive Agents; 0/Tumor Necrosis Factor-alpha; 50-35-1/Thalidomide; 6493-05-6/Pentoxifylline

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