NDT Advance Access published online on February 19, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh068
© 2004 by European Renal Association - European Dialysis and Transplant Association
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Catedra de Inmunologia, Escuela de Bioanalisis, Venezuela
* To whom correspondence should be addressed. E-mail: mosquera99{at}hotmail.com.
Background. The anti-apoptotic properties of melatonin have been demonstrated previously in several in vivo and in vitro studies. Previous reports have shown increased apoptosis during puromycin aminonucleoside nephrosis (PAN). The aim of this study was to determine if melatonin (MEL) can prevent apoptosis and modify oxidative stress, an apoptosis inducer, in this experimental model. Methods. Rats were injected intraperitoneally with puromycin aminonucleoside. In addition, by the intragastric route they received 1 mg/kg/day of MEL or vehicle 3 days before puromycin injection and throughout the experiment. Animals were sacrificed at weeks 1 and 2 of nephrosis and frozen renal sections were studied for apoptosis by TUNEL, for apoptosis-associated proteins by monoclonal and polyclonal antibodies, and for superoxide anion (O2-) by a histochemical method. Nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and catalase were measured in homogenized kidney tissue by appropriate biochemical and enzymatic methods. Results. Increases in apoptosis, p53, Fas and Fas-ligand were observed in nephrotic animals. MEL treatment decreased apoptosis at weeks 1 and 2 in the glomerular, interstitial and tubular compartments. This was accompanied by decreased expression of p53 (glomerulus, week 1; tubules, weeks 1 and 2), Fas (glomerulus and interstitium, week 2; tubules, weeks 1 and 2) and Fas-ligand (interstitum and tubules, week 2). Increased expression of Bcl-2-positive cells was observed at week 2 in all renal compartments in MEL-treated animals. High levels of O2- and NO generation and lipid peroxidation (MDA) were found in nephrotic animals. SOD and GSH remained unchanged, and only decreased catalase activity (week 1) was observed in PAN animals. Tendencies toward decreased values of O2- and MDA content along with recovery of catalase activity (week 1) were observed in MEL-treated nephrotic animals, but were insignificant in magnitude. MEL, however, did significantly downregulate pro-apoptotic genes and upregulated anti-apoptotic genes. Conclusions. The data demonstrate that, in PAN, melatonin has anti-apoptotic effects, which might in part be independent of the modulation of the oxidative status.
Accepted October 29, 2003
Original Article
Melatonin decreases apoptosis and expression of apoptosis-associated proteins in acute puromycin aminonucleoside nephrosis
2 Instituto de Investigaciones Clinicas ‘Dr Americo Negrette’, Facultad de Medicina, Venezuela
3 Instituto de Investigaciones Odontologicas, Facultad de Odontologia, Universidad del Zulia, Maracaibo, Venezuela
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Aoudjit, A. Potapov, and T. Takano Prostaglandin E2 promotes cell survival of glomerular epithelial cells via the EP4 receptor Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1534 - F1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wada, J. W. Pippin, C. B. Marshall, S. V. Griffin, and S. J. Shankland Dexamethasone Prevents Podocyte Apoptosis Induced by Puromycin Aminonucleoside: Role of p53 and Bcl-2-Related Family Proteins J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2615 - 2625. [Abstract] [Full Text] [PDF]
|
|