Effects of Intratracheally Administered Indium Phosphide on Male Fischer 344 Rats: Takamoto Uemura, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—Objective—To examine the effects of intratracheally administered indium phosphide (InP) and distribution of indium on male Fischer 344 rats. Materials and methods—Rats were intratracheally given 0, 1, 10 or 100 mg/kg of InP with a mean diameter of 0.8pm and observed for 1 and 7 days. The bronchoalveolar lavage fluid (BALF) was examined biochemically and cytologically. Serum biochemical, hematological and histopathological examinations were done, and the indium concentration in organs and serum was determined. Findings—The number of neutrophils in BALF remarkably increased in a dose‐effect manner 1 and 7 days after administration and InP particles were phagocytized in the macrophages. Total protein (TP), lactate dehydrogenase (LDH), total phospholipid (TPL) and total cholesterol (T‐Cho) in BALF showed a clear dose‐effect relationship 7 days after administration. Indium was detected in the liver and spleen and increased in a dose‐related manner on the next day and 7 days after administration. Serum indium was detected in the group given more than 10 mg/kg but did not reveal a dose relationship. Histopathological examination of the lungs showed phagocytized InP particles in the macrophages and the migration of neutrophiles in the alveoli. InP particles remained in the bronchioles and alveoli until 7 days after. No histopathological changes were detected in the liver or spleen. A hematological study did not reveal significant findings, interpretation—Intratracheally administered InP particles cause pulmonary inflammation and those particles remain in the lower airways for at least 7 days. Phagocytosis of macrophages may contribute to their disposal and distribution to the liver and spleen. Further study is required with particles with a lower toxic activity than InP and with the same particle size as the InP used in this study, to clarify their specific toxicity. Simultaneously longer observation is needed to assess toxicity in the other organs after distribution.

50 Sprague-Dawley rats were used to study the effect of allopurinol and prostaglandin E₁ (PGE₁) on renal ischemia-reperfusion injury. They underwent left renal ischemia for 1 h and reperfusion. A right nephrectomy was performed, and 5 groups were made. Group AP received allopurinol 50 mg/kg and PGE₁ 20 µg/kg; group A, allopurinol; group P, PGE₁; group C, control, and group S, sham group. Five animals from each group were used to study renal functions and 5 for renal histology. The serum creatinine values were lower in the treatment groups compared to the controls on days 1–3 and 7 (p < 0.05). The blood urea nitrogen values showed a similar trend. Maximum histological damage was seen in group C, followed by groups A, P and AP, in this order. We conclude that allopurinol and PGE₁ attenuate renal ischemia-reperfusion injury in rats.

To clarify the instillation toxicity of low level of indium phosphide (InP), 0, 1.2, 6.0 and 62.0 pg/kg body weight of InP particles were instilled intratracheally in male Fischer 344 rats, and the effects of InP were examined on the following day (day 1) and on the 8th day (day 8) after instillation. Indium was measured but not detected in the serum, liver, kidney, spleen, thymus and brain. Dose-related mild elevation of superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) were found on day 1 without increases of inflammatory cells and total protein (TP) in BALF, which suggested the response of neutrophils and alveolar macrophages to instilled InP, and/or the manifestation of a very early stage of inflammation. Only in the 62.0 pg/kg-instilled group on day 8, were neutrophils, lymphocytes, TP, LDH, total phospholipid and total cholesterol in BALF increased, and desquamation of alveolar epithelial cells and amorphous exudate in alveolar lumen observed by histopathological examination. These results suggested that InP caused pulmonary inflammation and epithelial cell damage up to 8 days following instillation dose of 62.0 pg/kg, but that its effect was considered irrelevant at instillation doses of 6.0 pg/kg or below in rat.

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