Effects of Repeated Intravenous Administration of Dextrans,Water-soluble Macromolecules, in Rats

Abstract

We investigated the influence of repeated intravenous administration of dextrans (DEXs) to rats. Seven-week-old Sprague Dawley rats (6 males/group) were given intravenously 10% saline solutions of dextrans (DEXs), 40 kDa or 200-300 kDa, at a dose level of 5 mL/kg/day for 28 days and they were examined histopathologically. Another group (3 males/group) was administered saline in a similar manner and served as the control. Histopathological changes indicating accumulation of DEXs in the mononuclear phagocyte system (MPS) and the liver were noted in the treated groups. The incidence and severity of the findings were molecular weight-dependent, except for the lungs. These results are considered useful in interpreting data from preclinical studies, in which DEXs or their derivatives are administered as test or control substances.

Keywords: intravenous administration; macromolecular substances; mononuclear phagocyte system.

Fig. 1.

Gross and histopathological findings in the lungs of SD rats intravenously administered DEXs for 28 days. Discolored white punctate foci were found on the lungs after formalin fixation. The severity of the lesions on the lungs in the DEX 40 kDa and 200–300 kDa groups was similar. (A, saline; B, DEX 40 kDa; C, DEX 200–300 kDa). Intra-alveolar aggregation of foam cells was seen in the lungs of all treated animals (D, a lung of a DEX 40 kDa treated rat; PAS, ×400).

Fig. 2.

Histopathological findings of the liver and spleen from SD rats intravenously administered DEXs for 28 days. Cytoplasmic vacuoles were stained blue with colloidal iron staining in the hepatocytes in a MW-dependent manner (A, saline; B, DEX 40 kDa; C, DEX 200–300 kDa; colloidal iron, ×400). In the DEX 200–300 kDa group, Kupffer cells were slightly to moderately hypertrophied (F, arrowheads) and increased in number, and they contained granules stained positively with PAS (D, saline; E, DEX 40 kDa; F, DEX 200–300 kDa; PAS, ×400). Foam cell infiltration was noted in some interstitial tissue (F, arrow). Aggregation of foam cells was noted in the splenic marginal zone and its adjacent area in the red pulp in a MW-dependent manner (G, saline; H, DEX 40 kDa; I, DEX 200–300 kDa; PAS, ×200).

Fig. 3.

Histopathological findings of the kidneys from SD rats intravenously administered DEXs for 28 days. Sparse foamy deposits in the glomeruli and sporadic foam cell infiltration in the cortical interstitial tissue were noted in the kidneys of the DEX 200–300 kDa group. PAS-positive granules were stained in the foamy deposits as in the case of foam cells (A, arrowheads; PAS, ×200). No changes were noted in the epithelium of the convoluted tubules. The foam cells in the cortical interstitial tissue and mesangial foamy deposits in the glomeruli were positive for ED1 in the kidneys (B, arrowheads; Immunohistochemistry for ED1, ×400).