Chronic dosing with aminoguanidine and novel advanced glycosylation end product-formation inhibitors ameliorates cross-linking of tail tendon collagen in STZ-induced diabetic rats

Diabetes ◽  
1996 ◽  
Vol 45 (12) ◽  
pp. 1694-1700 ◽  
Author(s):  
M. Kochakian ◽  
B. N. Manjula ◽  
J. J. Egan
2008 ◽  
Vol 46 (1) ◽  
pp. 280-285 ◽  
Author(s):  
Pon Velayutham Anandh Babu ◽  
Kuruvimalai Ekambaram Sabitha ◽  
Chennam Srinivasulu Shyamaladevi

2000 ◽  
Vol 1 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Sibel Özyazgan ◽  
Yesim Unlucerci ◽  
Selda Bekpinar ◽  
Ahmet Gökhan Akkan

AimThe effect of 8 weeks′ streptozotocin (STZ)- induced diabetes and aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction, treatment on arteriolar reactivity to vasoactive substances was investigatedin vitro.Materials and MethodsStudies were performed in untreated control rats (n= 10), STZ-induced (60 mg/kg i.v.) diabetic rats (n= 10), AMNG-treated (600 mg/l given in drinking water throughout 8 weeks) control rats (n= 10) and AMNG-treated (600 mg/l given in drinking water, beginning at 72h after STZ and throughout 8 weeks of diabetes) diabetic rats (n= 10). Results are expressed as the mean ±s.e. Relaxant responses are expressed as a percentage (%) relaxation of noradrenaline-induced tone. Statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparisons test.Results1. The decreased body weights (205 ± 6 g) and increased blood glucose levels (583 ± 8 mg/dl) of diabetic rats were partially restored by treatment of aminoguanidine (253 ± 6 g,p< 0.05 and 480 ± 14 mg/dl,p< 0.001, respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent relaxation to acetylcholine for noradrenaline precontracted aortas (p< 0.001). AMNG treatment prevented the diabetes-induced impairment in endothelium dependent relaxation (58 ± 8%) to acetylcholine, maximum relaxation remaining in the non-diabetic range (78 ± 4%). 3. Neither diabetes nor treatment affected endothelium-independent relaxation (pD2and max. Relax.) to sodium nitroprusside. 4. Vasoconstrictor responses (pD2and Max. Contraction) to noradrenaline and KCl were not influenced by the diabetic state and treatment.ConclusionOur data suggest that 8 weeks of experimental diabetes is associated with a decreased endothelium-dependent vasodilatation. AMNG treatment may prevent diabetes-induced endothelial dysfunction. This may be mediatedviathe prevention of advanced glycosylation end product formation, the enhanced release of vasodilator substances such as prostacyclin, the increased elasticity of blood vessels, the antioxidant activity and inhibitor activity of enzyme aldose-reductase by AMNG.


1973 ◽  
Vol 12 (3) ◽  
pp. 933-949
Author(s):  
R. W. COX ◽  
R. A. GRANT ◽  
C. M. KENT

Rat tail tendon collagen has been treated with the monoaldehydes, formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde and benzaldehyde, and with the dialdehydes, glyoxal and glutaraldehyde. The treated collagen was then examined in the electron microscope using a negative stain. Alterations to the native collagen pattern were seen with formaldehyde, acetaldehyde, propionaldehyde, glyoxal and glutaraldehyde. A correlation was noted between the changes in the band pattern and the degree of cross-linking estimated from chemical and physical changes in the treated collagen and from measurements of cross-linking made by other workers. The results indicate that the use of electron microscopy and negative staining may be a valuable method of assessing the degree of cross-linking in collagen treated with aldehydes and other reagent.


2020 ◽  
Vol 295 (31) ◽  
pp. 10562-10571 ◽  
Author(s):  
Melanie Stammers ◽  
Irina M. Ivanova ◽  
Izabella S. Niewczas ◽  
Anne Segonds-Pichon ◽  
Matthew Streeter ◽  
...  

Collagen is a structural protein whose internal cross-linking critically determines the properties and functions of connective tissue. Knowing how the cross-linking of collagen changes with age is key to understanding why the mechanical properties of tissues change over a lifetime. The current scientific consensus is that collagen cross-linking increases with age and that this increase leads to tendon stiffening. Here, we show that this view should be reconsidered. Using MS-based analyses, we demonstrated that during aging of healthy C57BL/6 mice, the overall levels of collagen cross-linking in tail tendon decreased with age. However, the levels of lysine glycation in collagen, which is not considered a cross-link, increased dramatically with age. We found that in 16-week-old diabetic db/db mice, glycation reaches levels similar to those observed in 98-week-old C57BL/6 mice, while the other cross-links typical of tendon collagen either decreased or remained the same as those observed in 20-week-old WT mice. These results, combined with findings from mechanical testing of tendons from these mice, indicate that overall collagen cross-linking in mouse tendon decreases with age. Our findings also reveal that lysine glycation appears to be an important factor that contributes to tendon stiffening with age and in diabetes.


1960 ◽  
Vol 235 (4) ◽  
pp. 989-994
Author(s):  
Alexander Kessler ◽  
Hyman Rosen ◽  
Stanley M. Levenson

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 39-47 ◽  
Author(s):  
Jeong Ho Lee ◽  
Dheerendra K. Reddy ◽  
Rajiv Saran ◽  
Harold L. Moore ◽  
Zbylut J. Twardowski ◽  
...  

Objective To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD). Study Design Thirty-three male Sprague–Dawley rats weighing between 275 – 300 g were divided into 5 groups: group C ( n = 6), control rats with catheter but not dialyzed; group D ( n = 5), diabetic rats with catheter but not dialyzed; group G ( n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H ( n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I ( n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. Results The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I ( p < 0.001, p = 0.001, and p < 0.05 respectively). Significant differences were also found between group G and groups D and I ( p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40 ± 0.01 vs 0.35 ± 0.01, p < 0.05); and between groups C and H for D/P urea (0.87 ± 0.03 vs 0.97 ± 0.02, p < 0.05). Conclusions These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.


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