A constant-flow, nonrecirculating system was used to study the extraction efficiency of colloidal carbon in the perfused liver of rats and rabbits. In both species, a diminution in perfusate flow produced an increased extraction efficiency. The extraction efficiency also increased with a decrease in the carbon concentration of the perfusate. In identical conditions regarding the flow rate and carbon concentration, the perfused liver of the rabbits showed a relatively lower phagocytic efficiency than that of the rats.
Jcl:SD rats were treated intraperitoneally with methylazoxy-methanol acetate (MAM acetate) at 0, 5 and 20 mg/kg dosage levels on day 14 of gestation, and were allowed to deliver spontaneously. Their offspring were examined for learning ability in a water T-maze at 10 weeks of age. Examinations of postnatal growth, development, reproductive performance, morphological alterations of the brain and other aspects of behavior were also carried out. The offspring of mothers that received 20 mg/kg of MAM acetate showed a slight decrease (less than 10%) of body weights from birth through adulthood, and slight decreases (2-22%) of liver, kidney, spleen and testis weights at 3 weeks of age as compared to the controls. They also showed slight delays in ear pinna separation, lower incisor eruption, eye and vaginal opening, but had normal appearances and reproductive performance. On the other hand, the cerebrum weights of the offspring in the 20 mg/kg group were approximately 50% less than controls. Microscopically, the micrencephalic offspring showed greatly reduced cerebral hemispheres and abnormal cortical cytoarchitecture. No significant differences were noted between the offspring of the 5 mg/kg of MAM acetate group and the control offspring. In an open-field behavioral tests, the offspring in the 20mg/kg group showed a decrease in the latent period and increases in the number of sections crossed and rearings. Their spontaneous night activity measured by a wheel cage increased as compared with controls. In the triple T-maze, the micrencephalic offspring made 1.4-2.8 times as many errors as controls did throughout trial days. There were no statistically significant differences in the behavioral parameters between the offspring in the 5mg/kg group and the control offspring. However, 2 animals in the 5 mg/kg group did not solve the maze problem within 10 minutes of the observation period while all controls successfully escaped from the maze.
Chloropeptide, a hepatotoxic mycotoxin of Penicillium islandicum Sopp, induces gross changes in cell morphology including blebbing and ballooning of the cytoplasmic membrane in the isolated hepatocytes, and this hepatotoxic potential of chloropeptide is abolished by microsomal cytochrome P-450 system.
The influence of NKK-105 on the acute toxicity of strychnine nitrate, potassium cyanide, chloral hydrate, atropine, tetrodotoxin, mercuric chloride, cadmium chloride, lead acetate and arsenic trioxide were examined in rats. NKK-105 prolonged the time of death induced by strychnine, potassium cyanide and tetrodotoxin in acute toxicity. Survival time was prolonged in rats treated with the toxic metals by pretreatment with NKK-105. NKK-105 counteracted the lethal effect of strychnine, potassium cyanide, chloral hydrate, mercuric chloride and cadmium chloride. NKK-105 significantly decreased the acute toxicity of these drugs but the inhibitory effect was not observed in the acute toxicity of atropine, tetrodotoxin, lead acetate and arsenic trioxide.
The effect of barbital intoxication on the neural energy reserve of rat was examined. The energy metabolism was depressed at dependent developing stage and recover to the non treated level at dependent stage. After with-drawal, rapid degradation of creatine phosphate and adenosine triphosphate was recognized. Later stage of withdrawal, the sum of creatine phosphate and adenosine triphosphate was decreased, and adenosine diphosphate and adenosine monophosphate was remarkably increased. These changes in neural energy reserve were parallel to the changes in adenylate cyclase activity and carbohydrate metabolism which were previously presentated. These changes may have possible role in development of drug dependence and or withdrawal.
For all members of the chlorinated ethane and ethylene series except monochloroethylene, the effects on the oxygen consumption of isolated rat mitochondria were studied. All the tested compounds inhibited glutamate and malate oxidation, and their inhibitory potency increased in the order of the number of contained chlorines. The eight compounds of greatest potency were also investigated for their inhibition of succinate oxidation in mitochondria and inhibition of NADH oxidation in sonicated submitochondrial particles. The data obtained suggested that the inhibition of substrate oxidation was due to blockade of electron transport and the most susceptible portion was located from NADH to CoQ.
The effect of TKPP on emesis was examined in adult "conditioned random source" mongrel dogs. Only dogs that exhibited emesis with CuSO4 were used. The effect of dosage and concentration of TKPP on emesis was highly significant. The effective combinations of dose and concentration were 4, 800, 2, 400, or 1, 200 mg/head at 5, 10, or 20%. In all the tested dogs, 4, 800mg of 20% TKPP was effective inducing emesis. The mean latency of emesis in dogs was 7 min, 33 sec (95% confidence limits : 5 min, 58 sec-9 min, 7 sec).