Observations on the polarographic characteristics and concentrations of protein and sialic acid in the serum of rats after intraperitoneal injections of polycyclic hydrocarbons.
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Iron appears to play a major role in catalysing free radical production, leading to lipid peroxidation and DNA damage. We, therefore, investigated the effect of colloidal iron deposited in the peritoneum. Wistar male rats were given either ferric saccharate, ferric saccharate and nitrilotriacetic acid (NTA), NTA or saline. NTA was shown previously to 'free' iron to promote lipid peroxidation and an iron chelate of NTA is known to be carcinogenic to the kidney. Iron at a dose of 5 mg kg-1 day-1, and saline at a dose of 0.5 ml day-1 were injected i.p. for 3 months. NTA at a dose of 83.5 mg kg-1 day-1 was give i.p. for 5 months. All the rats were killed about a year later for histological examination. In nine of the 19 rats treated with ferric saccharate, mesothelial tumors were induced in the serosa of the tunica vaginalis or the length of the spermatic cord. Among rats treated with ferric saccharate and NTA, seven had localised mesotheliomas in the above locations and six had wide-spread peritoneal mesotheliomas. No mesothelial tumors developed in either NTA treated or saline treated rats. No pleural mesotheliomas were found in any group. These findings add to the evidence that iron is involved in some carcinogenic processes.
Humans may be exposed to 2-aminoanthracene (2-AA), a substituted polycyclic aromatic hydrocarbon, and a recognized mutagen and carcinogen, through oral and respiratory routes from contact with a variety of environmental sources. For the present study, we sought to evaluate hepatic damage and recovery in Fischer 344 rats following multiple i.p. injections of 5 mg of 2-AA. Rats were injected weekly for up to 5 weeks. Subgroups were then allowed to recover for 1, 5, or 9 weeks, and biochemical and pathologic changes were evaluated. We observed that weight gains were reduced relative to controls for all groups receiving > or = 2 injections. Serum enzyme levels indicative of liver damage were evident and included alterations in serum aspartate aminotransferase, alkaline phosphatase, total protein, albumin, and globulin. These alterations usually returned to normal by 5 weeks following cessation of 2-AA administration. In contrast, histologic liver changes, including hepatocyte hypertrophy, biliary hyperplasia with oval cell proliferation, altered foci, nodular hyperplasia, and one hepatocellular adenoma became more severe with time. This experiment demonstrates patterns of hepatic damage and recovery in rats exposed to 2-AA.
Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose-related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose-related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS)
1. Shifts of enzymatic activity have been followed during the formation and evolution of the droplets that form in the cells of the proximal convolution of the nephron of the rat after the injection of a 50 per cent solution of egg white in isotonic saline. 2. Twelve hours after injection there is a 35 to 40 per cent decrease in succinoxidase and cytochrome oxidase activities in the fraction containing the larger particles; i.e. mitochondria and droplets in equal concentration. Although after 30 hours the quantitative proportion of droplets and mitochondria is the same as previously, the activities of the fraction have returned to the normal observed originally in the uninjected rat in a corresponding fraction consisting of mitochondria only. 3. The microsome fraction shows an average increase of 35 per cent in oxidative enzyme activities during the early period following injection, and decreases to the original figure in the later period of droplet formation. 4. It is concluded from the shifting pattern of localization of oxidative enzyme activity within the cell particulates that the absorption droplets arise by the incorporation of the mitochondrial elements, which originally contain the highest enzyme activity, with absorbed protein through the intermediate stage of smaller (microsomal) particles.
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Our objectives were to examine the effect of an i.p. injection of a flooding dose of l-phenylalanine (Phe) containing l-[ring-(2)H(5)]Phe on time courses of physiologic responses, the tracer Phe enrichments, and fractional protein synthesis rates (FSR) in plasma, visceral organs, and muscles. In a randomized complete block design, 5 blocks of 5 littermate piglets were weaned at 16 d of age and injected i.p. with a flooding dose of l-Phe (1.5 mmol/kg body weight) on d 8 postweaning under fed conditions. Tissues were collected at 15, 30, 45, 60, and 75 min postinjection. Plasma glucose concentration increased (cubic effect, P < 0.05) from 4.8 preinjection to 5.8 mmol/L 15 min postinjection and returned to preinjection levels thereafter. Plasma insulin concentration did not change (P > 0.05) over time. Plasma Phe concentration increased logarithmically (P < 0.05) from 85 to 711 micromol/L and reached 95% of the maximum concentration 48 min postinjection, but no changes (P > 0.05) in tissue contents of other free amino acids were observed. The Phe free pools in plasma, visceral organs, and muscles were evenly enriched (32.3 +/- 1.4 mol%) with l-[(2)H(5)]Phe 15 min after the i.p. injection. The FSR in visceral organs did not change (P > 0.05), whereas plasma and muscle protein FSR decreased (P < 0.05) over time. We conclude that the i.p. injected tracer Phe rapidly distributed into plasma and intra- and extracellular spaces, and was effective for measuring FSR in visceral organs, but not in plasma and muscles of pigs.
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Newborn rats were inoculated in the peritoneal cavity with Rous sarcoma virus (Schmidt-Ruppin strain). They were studied lymphographically and histologically after various intervals of time. As a result of lesions of the lymph vessels and nodes, the lymphatic drainage of the peritoneal cavity was increasingly impaired. Pleural effusion developed as a result of leakage through the walls of the lymphatics. The passage through the lymph nodes was blocked and large lymph cysts arose in the mediastinum and retroperitoneally.
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Interferon-alpha therapy is associated with a high rate of depression, but the pathophysiological mechanisms remain unclear. The purpose of the present study was to investigate the effects of i.p. administered interferon-alpha on monoaminergic neurotransmission in the brain. The levels of monoamines and associated metabolites were measured in various regions of the rat brain using a high-performance liquid chromatography-electrochemical detection system. The serotonin transporter mRNA levels were also measured using in situ hybridization. After 1 day, dopamine turnover was diminished in the cortex. Norepinephrine turnover was decreased in most regions tested after 4 days. However, these changes were transient. After 14 days, serotonin turnover was increased in the frontal cortex and hippocampus in rats given a dose of 20 000 IU/kg; in the frontal cortex, hippocampus, amygdala, thalamus, hypothalamus and brainstem in those on 200 000 IU/kg; and in the thalamus and hypothalamus in those on 2 000 000 IU/kg (all P < 0.05). However, 14-day treatment did not significantly change serotonin transporter mRNA levels. Next, the question of whether interferon-alpha affects monoamine levels via induction of nitric oxide (NO), was investigated. However, there were no changes in either NO2- or NO3-, as markers of NO production, in any brain regions after 14-day treatment. These results suggest that chronic peripheral administration of interferon-alpha induces metabolic changes in the central serotonin system. Further investigation is needed to determine exactly how this cytokine affects the central serotonin system and to assess whether a central serotonin abnormality is involved in interferon-induced depression.
The cocarcinogenic effects of asbestos are presented. In lung carcinomas induced in mice, the number of carcinomas and the time of detection of the first carcinoma per tumor-bearing animals were greater and faster in the group with chrysotile plus MNU than either chrysotile or MNU alone. This suggested that chrysotile asbestos had a promoting or cocarcinogenic effect on some carcinogens in the respiratory tract. In the group treated with chryotile alone, a tumor was found in the right pleural cavity at 15 months. This tumor microscopically was similar to the biphasic form of the human diffuse mesothelioma. Microvilli, basement membrane, and junctional apparatus were seen by electron microscope, but other cytoplasmic organelles of the tumor cells were relatively scanty. Two peritoneal tumors developed in gastric and intestinal serosa at 11 and 12 months. Light and electron microscopic studies suggested that the tumors were probably myosarcomas or fibrosarcoms.