The present study was designed to evaluate the pulmonary deposition and the effects of inhaled silica particles in the rat model. Wistar (W/M strain) rats were exposed to silica aerosols generated from a fluidized bed dust generator for 1 hr a day, intermittently for 6 days, using a "nose-only" inhalation chamber. After the cessation of the exposures, analysis of lavaged bronchoalveolar cells (BAC) and histological examinations of lungs and tracheobronchial lymph nodes (TBLN) were performed during a period of 6 months. Total cell yields and the proportions of alveolar macrophages (AM) in BAC were not altered, whereas the proportions of lymphocytes in BAC were significantly increased in the exposed animals. Although the proportions of silicaladen AM in BAC were gradually decreased during the 6 months, particle-laden AM were predominantly and persistently observed in the alveoli under light microscopy. Silica particles were also identified in macrophages of granulomatous nodules in pulmonary peribronchial lymphoid tissues (PBLT) and TBLN, indicating the translocation of particles via the lymph. Associated with pulmonary particle deposition, some characteristic histopathological features were evident, including thickening of alveolar duct bifurcations and lymphocyte infiltrations both in the alveolar sacs and around the interstitial blood vessels. At later months after the exposures, the alveolar interstitium was thickened with the increase of fibroblasts and collagen. These results implicate that short-term exposures of silica particles in the rat can evoke histopathologic changes in the lungs and lymphatic tissues, associated with their deposition and translocation.
Two glucosides to enhance histamine release from rat peritoneal mast cells were isolated from rhizomes of bracken fern (Pteridium aquilinum (L.) Kuhn). by column chromatography on Sephadex LH-20 and droplet counter-current chromatography, and named braxin A1 and A2. They were β-glucopyranosides with an aromatic structure in the aglycone moiety. They were appreciably unstable in activity and chemical structure, and were different from the active glucoside in the young fronds. Braxin A1 and A2 may well be identical with the toxic principles responsible for the bracken poisoning.
Distribution and forms of cadmium in the subcellular fraction after an intraperitoneal injection of Cd-metallothionein (Cd-MT) were studied to trace the metabolic fate of metallothionein in the kidney. Cd-containing components from the mitochondria, lysosomes and cytoplasm were gel filtered on Sephadex G-75 at 4, 24 and 72 hr after injection of Cd-MT. The chromatographic distribution patterns of cadmium were different among these three fractions and changed with time. At 4 hr a moderate amount of cadmium in the cytoplasm, and most of the cadmium in the lysosomes and mitochondria was bound to high molecular weight (HMW) proteins eluted in the void volume. At 24 hr almost all the cadmium in the cytoplasm became bound to metallothionein fraction, while most of the cadmium in the mitochondria and lysosomes was still bound to the HMW proteins. Since in the in vitro experiment the cadmium ions were nonspecifically bound to the HMW proteins, the longer term existence of cadmium in the HMW proteins in the lysosomes than in the cytoplasm after injection of Cd-MT, suggest that Cd-MT is degraded in the lysosomes, and that the inorganic cadmium ions liberated from the degraded proteins are bound to the HMW proteins. The present paper deals with the involvement of the lysosomes in the in vivo degradation of Cd-MT.
The interaction of ethanol and aflatoxin B1 (AFB1)-induced hepatotoxicity was studied in male Wistar rats using the activity of plasma GOT and GPT, liver triglyceride and histopathologic changes of liver necrosis as indices. Pretreatment of four oral doses of ethanol (4.0 g/kg BW each) at 48, 45, 24 and 21 hrs prior to AFB1 (0.5 to 2.0 mg/kg BW) single i.p. administration caused a significant increase in the activity of PGOT (6 folds) and PGPT (5 folds), liver triglycerides (2 folds) and severity of liver necrosis at 48 hrs after AFB1 administration. Ethanol pretreatment potentiated AFB1-induced hepatotoxicity by increasing MFO enzymes, aniline hydroxylase and P-nitroanisole-O-demethylase activity and lipid peroxidation, and decreasing in cytochrome b5, epoxide hydrolase activity and hepatic glutathione content. However, it did not cause any significant change in the activity of NADPH-cytochrome c reductase and glutathione-S-transferase and cytochrome P-450. These results suggest that potentiation of ethanol pretreatment on AFB1-induced hepatotoxicity may due to an increase in the metabolic formation of AFB1-2, 3-oxide and subsequent binding to DNA.
Wistar rats and ddY mice were fed diet containing 10 to 3000 ppm technical fenvalerate for the major portion of their life span. Microgranulomatous changes were observed in lymph nodes, liver and spleen of both rats and mice as well as in adrenals of rats. The no-effect level for microgranulomatous changes was 30 ppm for mice and 150 ppm for rats. Transmission electron microscopy of phagocytes in the granulomatous foci revealed needleor rod-shaped crystalline bodies within the cytoplasm. To examine reversibility of the microgranulomatous changes, ddY mice were fed the diet containing technical fenvalerate at the levels of 1000 and 3000 ppm for 6 weeks, followed by rearing on the control diet for up to 12 months. The size and number of the microgranulomatous changes were reduced with time. The microgranulomatous changes were typical of foreign body granulomas; they did not have the appearance of granulomas formed in response to immunologic stimulus.
Pulmonary changes were studied in Sprague-Dawley-rats dosed intravenously with various dosages around the LD 50 in acute studies, and with 0 (control), 0.001, 0.01 and 0.1 mg/kg b. wt./day St 91-Cl or with 0, 1, 5 and 25 mg/kg b. wt./day St 600-Cl for 4 weeks in subacute studies. Doses of 0.01 mg/kg St 91-Cl and 1 mg/kg St 600-Cl were well tolerated. At higher doses, both compounds caused acute pulmonary congestion, edema and bleeding. The acute changes obviously occurred after each single i. v. injection, and were followed by an intensive hemosiderosis of alveolar macrophages. All findings were reversible. No pulmonary changes were observed in oral subacute studies with both compounds.