Info

Kidney

Vacuolization of the proximal tubular epithelium 0 0 8 8

Red (hemogiobmogenous) casts 0 2 0 0

Focal basophilic changes and atrophy 12 11 of the renal tubules

Cellular infiltration in the interstitium 0 0 10

Pyelitis 0 0 10

Kidney

Vacuolization of the proximal tubular epithelium 0 0 8 8

Red (hemogiobmogenous) casts 0 2 0 0

Focal basophilic changes and atrophy 12 11 of the renal tubules

Cellular infiltration in the interstitium 0 0 10

Pyelitis 0 0 10

formaline and stained for histopathological examination. All protein solutions induced transient increases in AST and ALT, and a decrease in BUN (Fig. 6). The most remarkable increase in ALT was observed with PEG-Hb, while SNO-PEG-Hb showed the smallest increase. These changes in AST and ALT returned to the baseline at 3 days postinfusion. Histological examinations of the liver supported these biochemical observations (Table 1). In kidneys, unmodified Hb caused red casts immediately after the administration and increased the plasma creatinine level at 7 days postinfusion, suggesting that unmodified Hb was nephrotoxic. PEG-Hb and SNO-PEG-Hb caused vacuole formation in the proximal tubular epithelium. Cellular infiltration in the interstitium was observed in the PEG-Hb group, while this change was rare in the SNO-PEG-Hb group. Renal function, as evaluated by BUN and creatinine, was, however, normal in both Hb groups. These findings suggested that two pegylated Hb derivatives induced some transient stress with regard to hepatic and renal functions, but it seemed to be well tolerated.

The most remarkable observation in the histology was the vacuolization in the proximal tubular epithelium of the kidneys in the animals transfused with the two pegylated Hb products (Fig. 7 for histology of rats treated with SNO-PEG-Hb). A similar phenomenon has been reported by Matsushita et al.11, who showed that a PEG-Hb product caused vacuole formation in the epithelium of the canine kidney, without any pathological features of renal ischemic changes and the regeneration of the tubules. They demonstrated that these

Figure 7 Light microscopic examination of liver (left, x 66) and kidney (right, x 100) of rats treated with SNO-PEG-Hb at 7 days posdnftision. Hematoxylin and eosin stain.

vacuoles included iron, possibly derived from the Hb product, based on the data of elemental X-ray microanalysis and ferric iron staining. Other substances such as dextran, hydroxyethyl starch, sucrose and mannitol have been also shown to cause vacuolization without any disturbance in renal functions. These reports suggest that the vacuolization reflects the degradation process of artificial materials in the proximal tubule cells.

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