Effect of cross-linked chitosan iron (III) on vascular calcification in uremic rats

Abstract

Cross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups. We measured creatinine, phosphorus, calcium, alkaline phosphatase, phosphorus excretion fraction, parathyroid hormone, and fibroblast growth factor 23. Vascular calcification was assessed using the aortic calcium content, and a semi-quantitative analysis was performed using Von Kossa and hematoxylin-eosin staining. At week seven, rats in the chronic kidney disease group had higher creatinine, phosphorus, phosphorus excretion fraction, calcium, alkaline phosphatase, fibroblast growth factor 23, and aortic calcium content than those in the Control group. Treatments with cross-linked chitosan iron (III) and calcium carbonate prevented phosphorus increase (20%-30% reduction). The aortic calcium content was lowered by 88% and 85% in the CKD-Ch and CKD-sevelamer groups, respectively. The prevalence of vascular changes was higher in the chronic kidney disease and CKD-calcium carbonate (62.5%) groups than in the CKD-Ch group (37.5%). In conclusion, cross-linked chitosan iron (III) had a phosphorus chelating effect similar to calcium carbonate already available for clinical use, and prevented calcium accumulation in the aorta. Impact statement Vascular calcification (VC) is a common complication due to CKD-related bone and mineral disorder (BMD) and is characterized by deposition of calcium in vessels. Effective therapies are not yet available but new phosphorus chelators can prevent complications from CV. We tested the effect of chitosan, a new phosphorus chelator, on the VC of uremic animals. It has recently been proposed that chitosan treatment may be effective in the treatment of hyperphosphataemia. However, its action on vascular calcification has not been investigated yet. In this study, we demonstrated that chitosan reduced the calcium content in the aorta, suggesting that this may be a therapeutic approach in the treatment of hyperphosphatemia by preventing CV.

Evaluating the drug repurposing benefits of clopidogrel against adenine induced chronic renal failure in experimental animals

“…These changes may be due to the accumulation of uremic toxins, which cause inflammation and activate protein catabolic pathways, resulting in protein degradation, in addition to polyuria and dehydration (20). Treatment with CC-60 remarkably prevented the lowering of body weight and polyuria but, Vascular calcification, a metabolic disorder characterized by hyperphosphatemia, hypocalcemia, and hypermagnesemia, is often associated with CKD (22). In hemodialysis patients, vascular calcification is higher risk factor for CRF and is linked to elevated risk of irregular cardiovascular events (23).…”

Protective effects of lycopene against adenine-induced chronic renal failure in rats

“…[31] CKD also involves vascular calcification, a metabolic disorder manifested as hyperphosphataemia, hypocalcaemia, hypermagnesaemia and elevated levels of ALP. [32,33] Vascular calcification represents a greater risk factor for CKD in haemodialysis patients and is linked with an increased risk of abnormal cardiovascular events such as atherosclerosis, ischaemic heart disease and vascular stiffening. [34] Administration of adenine for 30 days increased serum phosphate, magnesium and ALP levels and reduced serum calcium concentrations.…”

Epoxy Chitosan-Crosslinked Acellular Bovine Pericardium with Improved Anti-calcification and Biological Properties

“…In addition, CS and its derivative were widely applied in tissue engineering including cartilage, skin, bone, liver, nerves, and muscle . de Castro reported that cross-linked CS iron­(III) had a phosphorus chelating effect, which could prevent calcium accumulation in the aorta . Besides, CS scaffolds and its derivative have been explored as small diameter vascular grafts in a sheep model by the Hibino group, and polycaprolactone/CS shows great potential application for cardiovascular disease treatment …”