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Biomedical subjects

Y R Kundomal

Publications and source records attributed to Y R Kundomal.

11 recordsLinked to original sources

Carcinogen bioassay of isoflurane in mice.

A carcinogen bioassay of isoflurane was performed in groups of Swiss/Webster mice exposed to either air (n = 181), 0.1% isoflurane (n = 167), or 0.4% isoflurane (n = 165), for 4 h per day, 5 days per week. After 78 weeks of exposure, mice were left untreated for 3 weeks and were then killed. Mice killed at this time when they were 86 weeks of age, and those killed or dying at other times during the study were subjected to complete gross and microscopic examination. Throughout most of the study, mean body weights of mice exposed to 0.1% isoflurane and 0.4% isoflurane were less by 1-5% and 5-8%, respectively, than that of mice exposed to air alone. Otherwise, no gross toxic treatment effects were noted. The first neoplastic lesion was detected 23 weeks after starting treatment and, by the end of the study, 190 tumors had been detected in 179 mice. However, there were no statistical differences among the groups in the number of mice with a particular tumor at a specific site, the ratio of benign to malignant tumors, or the time to tumor appearance. It was concluded that isoflurane is unlikely to have carcinogenic potential and is a remarkably non-toxic anesthetic in mice.

Animals↗

Mutagenicity of the combination of a volatile anaesthetic and nitrous oxide.

The mutagenic potential of halothane, enflurane and isoflurane in combination with nitrous oxide was investigated using the sex-linked recessive lethal assay in the fruit fly Drosophila melanogaster. Male wild-type flies were exposed for 1 h to 1 or 2% volatile anaesthetic with various concentrations of nitrous oxide up to 75%. They were then mated with untreated females of the Basc marker strain. A brooding pattern was used to assess mutagenicity at different germ cell stages. The rate of lethal mutations was assessed in the F2 generation. Halothane produced a dose-dependent increase in the rate of lethal mutations, but the mutagenicity was independent of the presence of nitrous oxide and of the stage of germ cell formation. Neither enflurane nor isoflurane was mutagenic in the presence of nitrous oxide.

Anesthesia, Inhalation↗

Cadmium content in selected rat tissues following treatments with cadmium chloride and/or gamma radiation.

This study was conducted to determine concentrations of cadmium (Cd) in various rat tissues; radiation effectiveness on Cd concentrations in rat tissues; and Cd effectiveness when radiation was applied as the second insult. Animals were subjected to Cd over a 29-day period and on Day 30 were exposed to an acute dose of 60Co gamma-ray. Rats were killed on Day 1, 7, or 21 following irradiation. Cd concentrations were determined by flame spectroscopy. Rats injected with Cd alone or Cd in combination with radiation showed a dose-dependent accumulation and retention of the metal in the liver and kidney over the intervals to sacrifice. Significantly smaller amounts of the metal were seen in the spleen, intestine, stomach, heart, testis, lung, blood, brain, and muscle. Generally, Cd did not afford protection against radiation in the tissues studied. Radiation, when used singly or as a coinsult with Cd, did not significantly alter the concentrations of Cd in any of the tissues studied except the heart, in which it contributed to the clearance of Cd. No synergistic or antagonistic effects were observed between Cd and ionizing radiation in any of the other tissues studied.

Animals↗

Carcinogen bioassay of nitrous oxide in mice.

A carcinogen bioassay of nitrous oxide (N2O) was performed in groups of male and female Swiss-Webster mice exposed to either air (n = 179), 10% N2O (n = 152), or 40% N2O (n = 151) for 4 h per day, 5 days per week. After 78 weeks of exposure, there was a 5-week period without treatment following which surviving mice were killed. Mice killed at this time or dying in extremis at other times were subjected to complete autopsy unless advanced autolysis or cannibalism precluded examination. Mean body weights for male and female mice in the 10% N2O group were the same as those in the air control group throughout the study, whereas they were 5% less in the 40% N2O group. Mean organ weights for N2O-treated mice were not statistically different from those of control mice. Gross and microscopic examination of tissues revealed a variety of neoplastic and nonneoplastic lesions; however, their presence was unrelated to treatment.

Adenoma↗

Toxicity and teratogenicity of inhaled anesthetics in Drosophila melanogaster.

The toxic and teratogenic effects of inhaled anesthetics were assessed in an in vivo assay using the fruit fly Drosophila melanogaster. Eggs were exposed during development (metamorphosis) to enflurane, isoflurane or halothane at a vapor concentration of 0.1 or 0.2% (v/v), to fluroxene at 0.025 or 0.05% (v/v), or to nitrous oxide at 20 or 40% (v/v). Flies produced in each group were counted and were examined for morphological abnormalities within one day of hatching. All the anesthetics except nitrous oxide produced a dose-dependent increase in the duration of metamorphosis and a decrease in the number of flies. Despite these effects on development, no morphological abnormalities were observed in any fly.

Abnormalities, Drug-Induced↗

Inhaled anaesthetics have no effect on fertility in Drosophila melanogaster.

The potential effects of enflurane, isoflurane, halothane, fluroxene and nitrous oxide on mortality and fertility in Drosophila melanogaster were examined. The LD50 value 1 day after exposure for 1 h was the same for males and females and was about 8% for enflurane, isoflurane and halothane, about 20% for fluroxene, and greater than 100% for nitrous oxide. Male and female fertility, however, were not affected by any of the anaesthetics, even at concentrations well above those used clinically.

Anesthesia, Inhalation↗

Mutagenicity of inhaled anesthetics in Drosophila melanogaster.

The mutagenic effects of several inhaled anesthetic agents were investigated using the sex-linked recessive lethal assay in the fruit fly, Drosophila melanogaster. Male wild-type flies were exposed for 1 hr to either halothane, enflurane, isoflurane, or fluroxene at vapor concentrations of 1 or 2% or to nitrous oxide at concentrations of 40 or 80%. Control flies were exposed to air alone. Following treatment, male flies were mated with untreated virgin females of the Basc strain and the rate of sex-linked recessive lethals was determined in the F2 generation. Halothane and fluroxene produced a dose-dependent and statistically significant increase in the rate of sex-linked recessive lethals, whereas enflurane, isoflurane, and nitrous oxide were not mutagenic at the concentrations tested.

Anesthesia, Inhalation↗

Effects of volatile anesthetics or fentanyl on hepatic function in cirrhotic rats.

Halothane, enflurane, isoflurane, and fentanyl were examined for their potential to exacerbate liver dysfunction in rats with preexisting cirrhosis. Male Wistar rats given sodium phenobarbital for 2 weeks are assigned randomly to two groups. One group (cirrhotic) was exposed by inhalation to carbon tetrachloride (CCl4) in air at weekly intervals for 12 weeks to induce cirrhosis. The other group (noncirrhotic) was handled similarly but received air only. Five weeks after the last exposure to CCl4, cirrhotic and noncirrhotic rats were given three hours of 1 MAC halothane, enflurane, or isoflurane in 50% oxygen, or 350 micrograms fentanyl per kg of body weight and 50% oxygen, or 50% oxygen only. Blood gas tensions and blood glucose levels were measured before, during, and at the end of exposure. Forty-eight hours after exposure, serum chemistries were measured in each rat for comparison with preexposure values. Rats were then killed by CO2 overdose, and liver, kidney, and testis were prepared for microscopic examination. Enflurane, isoflurane, and halothane, but not fentanyl, produced mild respiratory acidosis and no change in serum glucose levels. All anesthetics resulted in a mild but similar degree of acute liver dysfunction as indicated by small increases in SGOT or SGPT in both cirrhotic and noncirrhotic rats. Liver histology revealed mild to moderate portal cirrhosis with fibrosis and well-developed micronodules in rats exposed to CCl4, but no superimposed acute hepatocellular damage was noted. It is concluded that all the anesthetics used in this study were associated with the same minimal degree of postanesthetic hepatic dysfunction and that the dysfunction was similar in both cirrhotic and noncirrhotic rats.

Alanine Transaminase↗

Interaction of cadmium chloride and gamma irradiation on blood parameters of the young adult rat.

Two hundred and sixteen male Sprague-Dawley (S-D) rats, 80 +/- 5 days old and weighing 220-250 g each, were assigned at random to nine groups of 24 rats each. Rats were injected with cadmium (Cd) intraperitoneally every 3 days for 29 days for a total of nine injections. Injections doses were 0, 1.0, or 2.5 mg Cd kg-1 body wt. Twenty-four hours after the last Cd injection (Day 30), each rat received an acute whole-body 60Co gamma radiation dose of 0, 3.62, or 5.43 Gray (Gy) at a dose rate of 33.04 Gy min-1. The irradiated groups exhibited significant decreases in the total number of white blood cells (WBCs) and the percentage of lymphocytes. Significant increases were seen in the percentage of polyneutrophils, serum triacylglycerols (TG), serum iron, and serum lactate dehydrogenase (LDH). Cd-treated groups had increased total WBCs, percentage of polyneutrophils, and serum glutamate oxaloacetate transaminase (SGOT). Significant decreases were observed in the percentage of lymphocytes, hemoglobin, total number of red blood cells (RBCs), and hematocrit. In the co-insult, significant decreases were seen in the total number of WBCs and RBCs, the percentage of lymphocytes, hemoglobin, and hematocrit. Significant increases were observed in the percentage of polyneutrophils and serum iron. In general, Cd acted as a debilitator which enhanced the overall effect of ionizing radiation when applied as the second insult. On the other hand, Cd also provided protection against radiation; that is, some parameters such as total WBCs, serum TG, serum iron, and serum LDH were not as adversely affected by the co-insult as when radiation only was used. The mechanism of this Cd anomaly is not known.

Analysis of Variance↗

Effects of subchronic intermittent exposure to isoflurane in Swiss Webster mice.

Swiss Webster mice were treated to determine if subchronic intermittent exposure to the inhalation anesthetic isoflurane causes organ toxicity or enhances its own metabolism or that of other anesthetics. One-hundred twenty, four-week-old male and female mice were exposed to compressed air or to 0.02%, 0.1% or 0.5% of isoflurane for four hours per day, five days per week for nine weeks. Body weights among the groups were the same prior to exposure. Overall, there were no significant differences in body weights among exposure groups (ANOVA with day as a repeated measure: females - F = 2.12, P = 0.1085; males - F = 1.80, P = 0.1583). There was, however, a significant interaction of group and days; differences were isolated to the start of exposure (weeks 1 through 3 for females; week 2 for males). At all times, differences remained within 10% of the control body weights. Organ weights (liver, spleen, kidney, testis and uterus), hematocrits, and SGOT levels were similar among exposure groups. Histologic evaluation of organs revealed no anesthetic-related organ toxicity. The concentration of hepatic cytochromes, b5 and P-450, per mg of microsomal protein were similar among exposure groups and between sexes. The rates of hepatic microsomal metabolism (defluorination) of three volatile halogenated ether anesthetics (methoxyflurane, enflurane, and isoflurane) were not different among groups following nine weeks of exposure. Isoflurane exposures of 0.5% or less for four hours per day for five days per week would appear to be the maximum tolerated concentration for any chronic study. Since there was no evidence of organ toxicity or of enhanced or inhibited hepatic microsomal enzyme activity, isoflurane seems to be relatively non-toxic inhalation anesthetic under the conditions of this study.

Animals↗