Chitosan Iron(III) Reduces Phosphorus Levels in Alloxan Diabetes-Induced Rats with Signs of Renal Failure Development

Autor: Rafaela C. Dall’Oglio, Cristiani Bürger, Silvana Sandri, Lisiane M. R. Schöninger, Clóvis Antônio Rodrigues
Rok vydání: 2010
Předmět:
Zdroj: Basic & Clinical Pharmacology & Toxicology. 106:467-471
ISSN: 1742-7843
1742-7835
Popis: This study evaluates the effect of complex cross-linked chitosan iron-(III) (CH-FeCL) polymer as phosphate binder in renal failure induced by alloxan (150 mg ⁄ kg, i.p.) in rats. The animals (male and female) were divided into four groups and received the treatment once a day for 15 days: (i) control group, which received a single injection of saline (3 ml ⁄ kg, i.p.) and normal diet; (ii) alloxan group, which received only a dose of alloxan and normal diet; (iii) phosphate (PO4) group, which received diet supplemented with phosphate 1.2%; and (iv) CH-FeCL group, which received diet supplemented with phosphate 1.2% + CH-FeCL 0.5% (0.054% Fe elemental). It was observed that the CH-FeCL treatment did not alter body-weight, rela- tive weight of the organs and haematological parameters in the treated and control groups for both sexes. However, a decrease in serum phosphorus level of the CH-FeCL group was observed after 15 days, compared with the phosphate group in both sexes. The serum iron concentration of the CH-FeCL group did not differ from the control group in either sex. CH-FeCL polymer decreases intestinal phosphate absorption in rats with renal failure and is promising for the treatment of phosphate retention in patients with renal failure. Hyperphosphataemia is a hallmark of patients with end- stage renal disease and is associated with increased all-cause mortality, cardiovascular mortality and vascular calcification (1,2). These associations have raised the question of whether reducing phosphorus levels could result in improved survival. The normalization of phosphorus levels is often difficult and frequently not obtained. Data from the international Dialysis and Practice Patterns Study suggest that less than 50% of patients meet the target levels for serum phosphorus, and that this proportion has not changed substantially since 1999 (3). Furthermore, restriction of dietary phosphate often con- flicts with the need to maintain adequate protein intake, and the use of calcium-containing phosphorus binders increases the calcium burden, which can lead to episodes of hyper- calcaemia (4). In patients with chronic renal failure, several studies have found associations of both traditional risk factors, such as hypertension, hyperlipidaemia and diabetes and uremic- specific risk factors with vascular calcification. Most patients with progressive chronic renal failure develop hyperphosph- ataemia. Effective control of hyperphosphataemia, without increasing the total calcium load, has been correlated with attenuated progression of vascular calcification in dialysis patients (5). Therapeutic strategies aimed at phosphorus con- trol typically include dietary phosphorus restriction, reducing intestinal absorption with the use of phosphorus binders, and removing phosphorus with either dialysis three times weekly or daily peritoneal dialysis. The ideal phosphate bin- der should bind most dietary phosphate in the intestine with- out producing significant adverse effects; it also should be relatively inexpensive because most dialysis patients usually consume relatively large daily doses of the binder. Unfortu- nately, none of the currently used phosphate binders fulfil all these requirements (6). In recent years, several iron preparations have been developed as a possible and relatively inexpensive alterna- tive for lowering phosphorus serum levels (7). In this con- text, ferric chloride and ferric citrate have been used to control hyperphosphataemia in azotemic rats (8), and recently, iron-containing biopolymers have been described as possible drug carriers and controlled release beads for various drug models (9). To achieve this goal, many attempts were undertaken to increase the sorbent function- ality of the chitosan. The prospective method for this seems to be the cross-linking of polymer chains after complexa- tion with metal ions such as complex cross-linked chitosan iron(III) (CH-FeCL). CH-FeCL has been suggested as a phosphate binder, due to its ability to reduce intestinal absorption of phosphorus in normal (1) and hyperphospha- taemic rats (10). The present study sought to determine whether complex CH-FeCL is capable of adsorbing phosphorus in alloxan diabetes-induced rats with signs of renal failure development. For this, the phosphorous serum levels were monitored. The findings showed that CH-FeCL was able to reduce the phos- phorous serum levels in male and female rats.
Databáze: OpenAIRE
Externí odkaz: