Absorption of Iron Dextran . from the Peritoneal Cavity of Rats


Kazuyuki Suzuki, Zbylut J. Twardowski, Karl D. Nolph, Ramesh Khanna, Harold L. Moore

We investigated the absorption rate and acute toxicities of intraperitoneal iron dextran in rats. Eighteen Sprague-Dawley rats were divided into threegroups (n = 6). The animals were given standard 1.5% Dianeal (group 1) or 1.5% Dianeal containing iron in a concentration of 2 mg/L (group 2) or 10 mg/L (group 3) as iron dextran. First, a predialysis blood sample was obtained, and 25 mL of the designated dialysis solution was instilled into the peritoneal cavity. After a 6-hour cycle the dia~vsate was drained, and a postdialysis blood sample and specimen of the peritoneum were obtained. The iron concentrations of the dialysis solution, the dialysate, and both serum samples were determined. Histological samples were processed by hematoxylin and eosin and Prussian blue stain.

Results of the iron concentration (mg/L) of the dialysis solution, the dialysate, and the percent of the absorbed iron were as follows: group 1: 0.00, 0.20:1: 0.15, N/A; group 2: 2.24, 0.66:1: 2.8, 73.8 :I: 11.0; group 3: 9.84, 2.12:1: 0.62, 80.8:1: 5.7. The serum iron concentration did not change. No abnormal findings were found histologically.

More than 70% of the iron dextran was absorbed from the peritoneal cavity of the rats during a 6-hour peritoneal dialysis exchange. Intraperitoneal iron dextran may be an alternative route of iron delivery.

Key words

Intraperitoneal iron, iron dextran, serum iron

From:

Division of Nephrology, Department of Medicine, Harry S. Truman Veterans Administration Hospital and Dalton Research Center, University of Missouri, Columbia, Missouri, U.S.A.

Introduction

Functional iron deficiency is a common complication of erythropoietin replacement therapy for dialysis-associated anemia ( 1-3). Two different routes of iron delivery -intravenous injection and oral administration -are available. Intravenous treatment is inconvenient for peritoneal dialysis patients. Oral administration of iron is not always well absorbed and tolerated (4). Our former study showed the possibility of an alternative intraperitoneal route of iron delivery ( 5).

Iron dextran is commercially available and is widely used for dialysis patients (6-8). In spite of known anaphylactoid reactions to dextran (9) and hypotensive reactions to iron dextran complex ( 10), in our practice, iron dextran has been used safely in many dialyzed patients (6-8). The purpose of this study was to determine the absorption of iron dextran from the peritoneal cavity and its acute iron toxicity to the peritoneum in rats.

Materials and methods

Eighteen male Sprague-Dawley rats weighing 300 350 9 were divided into three groups (n = 6 each). Group I was control and given standard 1.5% dextrose solution (Dianeal PD-2; Baxter Healthcare, Deerfield, IL, U.S.A.). Groups 2 and 3 were study groups and given 1.5% dextrose dialysis solution containing iron in a concentration of 2 mg/L (group 2) or 10 mg/L (group 3) as iron dextran.

At the beginning of the experiment, the animal was anesthetized with Metofane (Pitman-Moore, Mundelein, NJ, U.S.A.) and placed in the supine position. A predialysis blood sample (2 mL) was taken through direct cardiac puncture, and 25 mL of the designated dialysate was injected into the peritoneal cavity by direct peritoneal puncture through a 22-gauge needle within 2 min. Then the animals recovered from anesthesia spontaneously and completely, and were allowed free access to standard rat chow and tap water. Just before the 6-hour cycle time, the animal was reanesthetized and placed in the supine position. The injected dialysate was drained as completely as possible through an indwelling catheter. Then the abdomen was opened and the residual dialysate was collected. Once again, a postdialysis blood sample (2 mL) was obtained through direct cardiac puncture. A small specimen of the visceral peritoneum was taken for examination of iron deposition.

Iron concentration of pre-dialysis serum and post-dialysis serum was measured by quantitative colorimetric enzyme assay (Iron UIBC Kit, Sigma Diagnostics, St. Louis, MO, U.S.A.). The iron concentration of the fresh dialysis solution, the dialysis solution with added iron dextran, and the drained dialysate was determined by atomic absorption. Histological samples were processed with hematoxylin-eosin and Prussian blue stain.

Results

Iron concentration of the dialysis solution (mg/L), dialysate (mg/L), drained volume (mL), and the percentage of the iron absorbed are shown in Table I. More than 70% of the injected iron dextran was absorbed with a 6-hour cycle in both groups 2 and 3. There was not a significant difference between the three groups concerning total volume of the drained and residual dialysate. The iron concentration of pre serum and postserum of the rats is shown in Table II. There were no significant differences between the three groups or between the pre-dialysis serum and post-dialysis serum samples.

On gross examination no apparent changes of the peritoneum were observed. On histological examination no iron deposits were found in specimens from groups 2 and 3. No inflammatory changes were observed in any groups.

Discussion

In this study we demonstrated that more than 70% of the iron, as iron dextran, injected into the peritoneal cavity of the rats was absorbed with a 6-hour cycle.

The amount of the absorbed iron was a little greater than it was from ferric chloride (5). This suggests that iron with macromolecules may be effectively absorbed through lymphatic pathways. Therefore, we may conclude that iron dextran would be well absorbed from the peritoneal cavity.

We could not find a remarkable change in serum iron concentration in study groups with the 6-hour cycle time, probably because the overall amount of absorbed iron was small. We did not find iron deposition or iron trapping by the mesothelial cells on histological examination. We found no inflammatory changes either. Thus we presume that there would be no acute toxicity of iron dextran.

In conclusion, we injected iron dextran into the peritoneal cavity of rats. More than 70% of the iron was absorbed. We did not find any sign of acute iron toxicity to the peritoneum. Chronic absorption and toxicity studies are now needed to determine whether intraperitoneal iron could be an alternative method of iron delivery in peritoneal dialysis patients.

Acknowledgment

This study was supported in part by Nephrology Research Fund and by a grant from Amgen (Thousand Oaks, CA, U.S.A.).

References

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Corresponding author:
Zbylut J. Twardowski,MD, MA436 Health Sciences Center, University ofMissouri, Columbia, Missouri 65212 U.S.A.