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By reducing TGF beta 1, octreotide lessens the peritoneal derangements induced by a high glucose solution
1Department of Nephrology, Firat University School of Medicine, Elazig, Turkey. igunal@yahoo.com
Background:
Chronic peritoneal dialysis may eventually result in peritoneal fibrosis, which progressively reduces dialytic efficacy. Although the pathogenesis has not been elucidated, it has been proposed that transforming growth factor beta-1 (TGF beta 1) plays a central role in the onset of peritoneal fibrosis.
Methods:
Rats were divided into three groups and given saline, hypertonic peritoneal dialysis solution alone, a hypertonic peritoneal dialysis solution plus octreotide intraperitoneally. After four weeks, a one-hour peritoneal equilibration test was done. Dialysate-to-plasma urea ratio, glucose reabsorption, ultrafiltration volume and levels of dialysate protein, TGF beta 1 and cancer antigen 125 (CA 125) were determined. The peritoneal membrane was examined histologically by light microscopy.
Results:
Compared to the saline group, peritoneal function tests (ultrafiltration volume 6 (5-7) vs 0.0 ml, dialysate-to-plasma urea ratio 0.51 vs 0.76, glucose reabsorption 0.54 vs 0.40 and morphology (thickness 4.5 vs 75.5 microns) were dramatically deranged in hypertonic peritoneal dialysis solution-treated rats, which also had a higher level of TGF beta 1 and undetectable CA 125. In contrast, in hypertonic peritoneal dialysis solution plus octreotide rats' peritoneal function was protected (ultrafiltration volume 3 mL, dialysate-to-plasma urea 0.60, glucose reabsorption 0.51) but peritoneal thickening (37.7 microns) was not so markedly reduced although the production of TGF beta 1 was significantly inhibited.
Conclusion:
These data show that by inhibiting the production of TGF beta 1, octreotide can preserve peritoneal function and remodeling of the mesothelial cell. Although the production of TGF beta 1 was significantly inhibited, peritoneal thickening cannot be completely prevented.
Insights
Octreotide preserves peritoneal dialysis function by inhibiting transforming growth factor beta-1 (TGF-β1). While TGF-β1 production is reduced, some peritoneal thickening persists.
Area of Science:
- Nephrology
- Cell Biology
- Medical Research
Background:
- Chronic peritoneal dialysis can lead to peritoneal fibrosis, impairing dialysis efficacy.
- Transforming growth factor beta-1 (TGF-β1) is implicated in the development of peritoneal fibrosis.
Purpose of the Study:
- To investigate the protective effects of octreotide on peritoneal function and fibrosis in a rat model.
- To assess the role of TGF-β1 inhibition by octreotide in preventing peritoneal dialysis-induced changes.
Main Methods:
- Rats received saline, dialysis solution alone, or dialysis solution with octreotide.
- Peritoneal function was assessed via peritoneal equilibration tests.
- Levels of TGF-β1, CA 125, and peritoneal membrane histology were analyzed.
Main Results:
- Dialysis solution alone caused significant peritoneal dysfunction and thickening, with elevated TGF-β1.
- Octreotide treatment partially preserved peritoneal function and reduced peritoneal thickening.
- Octreotide significantly inhibited TGF-β1 production but did not completely prevent peritoneal thickening.
Conclusions:
- Octreotide, by inhibiting TGF-β1, can preserve peritoneal function and mesothelial cell remodeling during dialysis.
- Complete prevention of peritoneal thickening was not achieved despite significant TGF-β1 inhibition.