Effect of Iron(III) Chitosan Intake on the Reduction of Serum Phosphorus in Rats

Abstract

Because of the widespread use of aluminium- and calcium-containing phosphate binders for the control of hyperphosphataemia in patients with end-stage renal failure, an iron(III) chitosan complex was synthesised and fed to rats to measure its effect on serum phosphorus and calcium, intestinal phosphate binding and phosphate absorption. Thirty-six Wistar rats were randomly selected and distributed into a baseline group (n = 6), a control group (n = 8 (days 0-15), n = 8 (days 16-30)) and a treatment group (n = 8 (days 0-15), n = 8 (days 16-30)). The control groups ingested AIN-76 diet mix with a 1% w/w fibre content; however, the treatment groups had the fibre content completely substituted with iron(III) chitosan. The mean weights of the treated rats were slightly lower from 15 days (not significant); but overall, rat growth was not stunted in the treatment groups. The serum phosphorus levels of the treated group (n = 8) were significantly reduced after 15 days (P = 0.004; control: 5.7+/-0.9 mg dL(-1); treatment: 4.4+/-0.5 mg dL(-1); 95% CI of difference: 0.5-2.2) and 30 days (P = 0.002; control: 5.5+/-0.9 mg dL(-1); treatment = 4.1+/-06 mg dL(-1); 95% CI of difference: 0.6-2.3) as compared with the respective control group. The serum calcium-phosphorus product was 62.0+/-12.1 mg2 dL(-2) for the control and 45.1+/-6.6 mg2 dL(-2) for the treatment group after 30 days (P = 0.004). The serum iron concentration of the treatment group did not differ from the baseline value after 15 and 30 days, but the treatment group was significantly higher than the control group (P<0.05) after 30 days. The faeces phosphorus levels (mg day(-1)) were higher (P<0.01) and its iron content was much higher (P<0.01) for the treated group. The urine phosphorus (mg kg(-1)) was not significantly reduced for the treated group, but the mean was consistently less. The kidney and liver weights of both groups were similar, but the phosphorus content of the kidney (mg (g kidney)(-1)) was higher for the treated group after 30 days (P = 0.041; control, 4.2+/-1.2 mg g(-1) vs treatment, 5.6+/-1.4 mg g(-1). Because iron(III) chitosan had a high phosphorus-binding capacity of 308 (mg P) per gram of Fe3+ for both the in-vitro (pH 7.5) and in-vivo studies, which is greater than nearly all commonly used phosphate binders, and a small net phosphorus absorption difference of 3.7 mg day(-1), it is an efficient phosphate binder for lowering serum phosphate levels without increasing serum calcium levels.

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

“…These results are different from those reported by Baxter et al. [1], which reported a significant difference between serum iron concentration in normal rats fed with chow containing iron chitosan complex (1% w/w) (treated group) over a 30‐day period and the control group fed with normal chow. Hsu et al.…”

“…Thus, the chemical cross-linking of chitosan with glutaraldehyde occurs by a Shiff's reaction on aldehyde groups on glutaradehyde with a free amine group from chitosan that results in the insolubility of polymer in acid pH (stomach) and consequent release of the iron of polymer into the circulating blood. These results are different from those reported by Baxter et al [1], which reported a significant difference between serum iron concentration in normal rats fed with chow containing iron chitosan complex (1% w ⁄ w) (treated group) over a 30-day period and the control group fed with normal chow. Hsu et al also showed an increase of 60% in serum iron concentration in azotemic rats fed with a diet supplemented with ferric citrate (4% w ⁄ w) after 30 days [8].…”

“…Baxter et al. also showed that normal rats fed with chow modified with chitosan‐iron complex (1% w/w) presented a reduction in phosphorous serum levels [1]. These results may be explained by the stability constant of the complex formed between iron and phosphate.…”

“…The prospective method for this seems to be the cross-linking of polymer chains after complexation 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 hyperphosphataemic rats [10].…”

Chitosan‐Fe (III) Complex as a Phosphate Chelator in Uraemic Rats: A Novel Treatment Option

“…CH‐FeCl combines the chelation properties of chitosan and iron, without the risk of increased iron availability and consequent toxicity. This compound has been shown to reduce phosphate absorption in the intestine of diabetic rats with hyperphosphataemia induced by diet phosphorus overload . However, in those studies, the animals did not have CKD or CKD‐MBD, which limits the clinical usefulness of the results.…”