Effects of low molecular weight heparin in obstructed kidneys: decrease of collagen, fibronectin and TGF-β, and increase of chondroitin/dermatan sulfate proteoglycans and macrophage infiltration

Pecly, Inah Maria Drummond; Gonçalves, Raquel Garcia; Rangel, Ednei P.; Takiya, Christina Maeda; Taboada, Fernanda S.; Martinusso, Cesonia A.; Pavão, Mauro S.G.; Leite, Maurilo

doi:10.1093/ndt/gfk076

Cited by 34 publications

(25 citation statements)

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“…Slices were stained with 1% alcian blue (8GX, Sigma, St. Louis, MO, USA) at pH 2.5 in a 0.1 M HCl solution for -nique Spach, 1987, 1993) for collagen stain--etry was performed using an imaging analysis sysTokyo, Japan) coupled to a light microscope (Eclipse stained with Sirius red and Weigert's resorcin fuchsin -ity images (buffer: 2,048 x 1,536 pixels) by considering the percentage of stained areas in the total histological Silver Spring, MD, USA). Results were expressed as sur-2 ) (Pecly et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Paraquat (PQ)-induced pulmonary fibrosis increases exercise metabolic cost, reducing aerobic performance in rats

et al. 2009

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-Rats exposed to the quaternary herbicide paraquat (PQ) exhibit oxidative stress and lung injury. In the present study, we investigated the effect of multiple exposures to PQ on aerobic performance during progressive exercise on a treadmill in rats. PQ was dissolved in saline (SAL) (10 mg/ml) and administered intraperitoneally 7 mg/kg body wt to Wistar rats (n = 5) once a week for one month. Control rats received SAL (0.7 ml/kg body wt., intraperitoneally, n = 5) over the same time period. The animals were submitted to aerobic evaluation on a treadmill using a progressive protocol until fatigue prior to the removed and divided in two groups: PQ and SAL for histopathological analysis. The animals exposed to -gen consumption during exercise in comparison to the controls forty days after the last dose of PQ. Lung -parenchyma were higher in PQ compared to SAL. In conclusion, multiple exposures to PQ induce pulmoof exercise in rats.

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Section: Introductionmentioning

confidence: 99%

Paraquat (PQ)-induced pulmonary fibrosis increases exercise metabolic cost, reducing aerobic performance in rats

et al. 2009

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“…In subtotal nephrectomized rats, heparin ameliorates glomerular sclerosis and interstitial fibrosis (1). Low-molecular-weight heparin decreases proteinuria in adriamycin-induced renal disease (3) and attenuates fibrosis in the unilateral ureteral obstruction model in rats (21).…”

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confidence: 99%

Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: a P-selectin-mediated event?

Melo-Filho

Belmiro

Gonçalves

et al. 2010

American Journal of Physiology-Renal Physiology

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Melo-Filho NM, Belmiro CL, Gonçalves RG, Takiya CM, Leite M Jr, Pavão MS, Mourão PA. Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: a P-selectin-mediated event? Am J Physiol Renal Physiol 299: F1299 -F1307, 2010. First published September 22, 2010 doi:10.1152/ajprenal.00217.2010.-Fibrosis is the end point of most renal diseases, and several glycosaminoglycans have been shown to attenuate this process. Marine invertebrate glycosaminoglycans with unique structures have opened the possibility to test these new compounds on renal fibrosis. The effect of a fucosylated chondroitin sulfate from an echinoderm marine species is reported with the use of a model of renal fibrosis in rats, termed unilateral ureteral obstruction. Animals were given 4 mg/kg body wt of fucosylated chondroitin sulfate intraperitoneally, once a day. After 14 days, their kidneys were examined by histological, immunohistochemical, and biochemical methods. Compared with control mice, collagen deposition decreased in the course of renal fibrosis in the animals receiving fucosylated chondroitin sulfate, as revealed by Sirius red staining and hydroxyproline content. The cellularity related to myofibroblasts and macrophages was also reduced, as was the production of transforming growth factor (TGF)-␤. The glycosaminoglycan content increased in the renal interstitium of animals submitted to unilateral ureteral obstruction compared with the control contralateral kidney, mostly due to an increase of chondroitin sulfate content. Interestingly, no change in the pattern of glycosaminoglycan deposition was observed after administration of fucosylated chondroitin sulfate. Fibrosis induced by unilateral ureteral obstruction is attenuated in P-selectin-deficient mice, which also do not respond to the invertebrate glycosaminoglycan. In conclusion, fucosylated chondroitin sulfate attenuates renal fibrosis on a ureteral obstruction model in mice preponderantly through a P-selectinmediated mechanism.glycosaminoglycans; inflammatory cells; anti-selectin activity; cytokine expression; collagen accumulation THE PROGRESSION OF RENAL DISEASES has increasingly challenged investigators to test new therapeutic approaches to halt the progression of renal interstitial fibrosis. The initial aspect of the progressive renal disease may differ. Glomerular diseases may progress to glomerular sclerosis and scarring, whereas tubular diseases may develop to tubulointerstitial fibrosis. However, as the disease progresses in both circumstances, renal interstitial fibrosis is the predominant pathological outcome (15).The use of glycosaminoglycans as anti-inflammatory agents has been tested in different models of renal disease. In subtotal nephrectomized rats, heparin ameliorates glomerular sclerosis and interstitial fibrosis (1). Low-molecular-weight heparin decreases proteinuria in adriamycin-induced renal disease (3) and attenuates fibrosis in the unilateral ureteral obstruction model in rats (21).Sulfated polysaccha...

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“…[11][12][13][14][15] The continuing decrease in baseline plasma TGF-b1 concentration observed in our trial is in agreement with the experiment showing that sulodexide was capable of suppressing TGF-b1 gene overexpression within the diabetic kidneys, 22 similar to the actions of heparin in other nephropathies. [23][24][25] The behavior of plasma TGF-b1 following IV sulodexide administration has not been studied before. However, the growth factor level was found to increase during hemodialysis in chronic renal failure patients anticoagulated with a low-molecular-weight heparin enoxaparin for blood purification procedures.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sulodexide on Plasma Transforming Growth Factor-β1 in Healthy Volunteers

Borawski

Dubowski

Pawlak

et al. 2008

Clin Appl Thromb Hemost

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It is unknown whether the glycosaminoglycan drug sulodexide interferes with transforming growth factorb1-a member of heparin-binding family and a potent regulator of human biology and diseases. Hence, a 2-week pilot study was performed in 11 healthy men. Sulodexide was initially administered intravenously in a single dose, then-orally for 12 days and-again intravenously on study completion. Initial injection had no effect on activated form of the growth factor measured in plasma after 10 and 120 min; no change was also observed after 120 min from drug ingestion on day 7.On final intravenous administration, the growth factor levels increased by almost 60% after 10 min and remained elevated; the 120-min levels directly correlated with sulodexide dosage. Baseline cytokine levels decreased during the 2-week trial by more than 50%. In conclusion, transforming growth factor-b1 release and likely downregulation of its expression may constitute novel pharmacological effects of sulodexide.

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Effects of low molecular weight heparin in obstructed kidneys: decrease of collagen, fibronectin and TGF-β, and increase of chondroitin/dermatan sulfate proteoglycans and macrophage infiltration

Cited by 34 publications

References 31 publications

Paraquat (PQ)-induced pulmonary fibrosis increases exercise metabolic cost, reducing aerobic performance in rats

Paraquat (PQ)-induced pulmonary fibrosis increases exercise metabolic cost, reducing aerobic performance in rats

Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: a P-selectin-mediated event?

Effect of Sulodexide on Plasma Transforming Growth Factor-β1 in Healthy Volunteers

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