Effects of ethionine on tRNA methylation in male and female rats

Administration of hepatocarcinogens to rats results in an increase in tRNA methyltransferase activity in the target tissues. Ethionine is active as a carcinogen only in female rats and only in females is this increase in enzyme activity seen. However, ethionine also causes the formation of methyl-deficient tRNA in the liver. Other hepatocarcinogens do not do this. Ethionine is equally effective in this action in males and females. Thus, the two actions of ethionine are completely separable, and the methyl-deficiency of tRNA is caused by an activity not identical with the carcinogenic one.     

Effects of growth, degeneration and regeneration on the sensory motor system

Evidence was presented for regeneration and growth in the central nervous system of experimental animals and in the peripheral nervous system of man. Neurophysiological, neurohistological and neurochemical findings from the cerebellothalamocortical and the nigrostriatal projection systems as well as the motoneurons of the anterior horn and facial nucleus were presented and their possible functional implications discussed. Single unit recordings from regenerated primary afferents in human peripheral nerves were also shown and discussed in the light of their clinical relevance. The conclusions were reached that the findings of positive growth in the CNS following traumatic injury or in response to brain implants left little doubt that the CNS possesses the intrinsic capability of regeneration. The functional and clinical implications of this inherent capacity awaits further research. Recording the response behavior of regenerated primary afferents in man, on the other hand, provided more direct insight into functional deficits and their clinical correlates.     

Differential expression of hepatocyte growth factor in liver, kidney, lung, and spleen following burn in rats

Hepatocyte growth factor (HGF) plays a role as an organotropic factor for regeneration of injured organs. HGF is synthesized as an inactive single-chain precursor which is then converted to a biologically active heterodimeric form by proteolytic processing. Burn is the insult that results in hypovolemia which causes systemic organ injury. In this study, we investigated the induction and activation of HGF in various rat organs following burn trauma. Tissue HGF content determined as the total amount of the single-chain and heterodimeric form increased significantly in liver, lung, spleen, and kidney 12 h after burn. Molecular analysis revealed that HGF in these four organs of control rats was the single-chain precursor. In the burned rats, HGF was the single-chain form in the liver and lung, whereas heterodimeric HGF was detected in the spleen and kidney. Tissue protein content, an index of tissue injury, decreased significantly in the spleen and kidney, indicating that tissue damage was severe in these two organs. These results suggest that burn induces the production of HGF in various organs, and that the induced HGF is activated according to the severity of tissue damage caused by burn.     

Effects of testosterone and estradiol on serum somatomedin A and growth rate of rats

The mode of involvement of sex steroids in the growth spurt during adolescence was studied in Wistar rats with a special reference to the level of serum somatomedin A (SMA) determined by radioreceptor assay. Intramuscular administration of testosterone propionate (T; 1 mg/day, alternately for 10 days) to female or gonadectomized male rats provoked a small but significant increase in their body weight or body length without affecting the serum SMA level. In contrast, in hypophysectomized (hypox) male rats T caused a considerable increase in body weight and the serum SMA level only when administered concurrently with bovine growth hormone (bGH; 0.2 U/day, ip). T did not affect the sulfation activity in vitro. These results suggest that androgen participates in the growth spurt during adolescence by enhancing the SMA effect and/or potentiating the SMA production by GH. Estradiol benzoate (E2; 100 micrograms/day, alternately for 10 days) caused a decrease in the serum SMA level and the growth rate in normal male rats. However, E2 produced an increase in the SMA level when administered to hypox male rats, although the growth was retarded and sulfation potency of the serum was sharply reduced. These results indicate that E2 may suppress the growth by lowering SMA generation in normal rats and cause a production of biologically inactive SMA in hypox male rats.     

Dietary alterations in protein,carbohydrates and fat increase liver protein-turnover rate and decrease overall growth rate in the rainbow trout (Oncorhynchus mykiss

We have determined the protein-turnover rates and nucleic-acid concentrations in the liver of trout (Oncorhynchus mykiss) fed on two different isocaloric diets: low-protein/high-fat and non-carbohydrate/high-fat. Compared to controls, the partial replacement of protein with fat significantly decreased the protein accumulation rate and protein-retention efficiency in the liver whilst increasing the fractional protein-synthesis and protein-degradation rates as well as protein-synthesis efficiency. The complete replacement of carbohydrates with fat significantly lowered the protein-accumulation rate and protein-retention efficiency, but enhanced both the protein-synthesis and protein-degradation rates as well as protein-synthesis capacity. The protein:DNA and RNA:DNA ratios decreased considerably on both diets. Total DNA decreased in fish on a low-protein/high-fat diet but did not change in those on a non-carbohydrate/high-fat diet. The absolute protein-synthesis rate registered no significant change under any of the nutritional conditions. Both the experimental diets did however raise the fractional protein-synthesis rate significantly, due to enhanced protein-synthesis efficiency when protein was partially replaced with fat and to enhanced protein-synthesis capacity when carbohydrates were completely replaced with fat. Our results show the capacity of the liver to adapt its turnover rates and conform to different nutritional conditions. They also point to the possibility of controlling fish growth by dietary means.     

Mitochondrial respiration in heart, liver, and kidney of copper-deficient rats

Morphological observations in some tissues indicate that dietary copper deficiency results in structural damage to mitochondria. The purpose of this study was to determine whether mitochondrial function is impaired as well. Male, weanling Sprague-Dawley rats were fed diets deficient or sufficient in copper for 4 weeks. Mitochondria were isolated from heart, liver, kidney cortex, and kidney medulla. P/O ratio, state 3 and state 4 respiration rates (oxygen consumed in the presence and absence of ADP, respectively), and acceptor control index (ratio of state 3:state 4) were determined using succinate or pyruvate/malate as substrate. State 3 respiration rate in mitochondria from copper-deficient hearts and livers was lower than in mitochondria from copper-sufficient hearts. Copper deficiency reduced the state 4 respiration rate only in cardiac mitochondria. Neither respiration rate was affected by copper deficiency in mitochondria from kidney medulla or cortex. P/O ratio was not significantly affected by copper deficiency in any tissue examined. Acceptor control index was reduced only in liver mitochondria. The observed decreases in respiration rates are consistent with decreased cytochrome c oxidase activity, shown by others to occur in mitochondria isolated from hearts and livers of copper-deficient rats.     

Chronic effects of cadmium on kidney,liver, testis,and fertility of male rats

Male Wistar rats (n:20), at 5 wk of age, were given cadmium in drinking water (10 mg/L water) for 52 wk; 8 males and 20 female rats, as controls, were given tap water. At the end of 28 and 40 wk, some of the cadmium-treated males and control group male rats were sacrificed for the histopathological examination of testis, kidney, and liver. At the end of 56 wk, histopathological examinations were performed in the same way. Liver, kidney, and testis cadmium levels were also determined by atomic absorption spectrophotometry. All the cadmium-treated male rats showed pathological testicular alterations, and liver and kidney damage after chronic exposure. Cadmium levels were found to be highest in the kidney (1.009 +/- 0.034 microgram/g wet tissue in the infertile group). At the end of the 52-wk period, reproductive capacity of the cadmium-treated rats was investigated and was found to be lost in 39.89% of the animals.     

Different effects of 1,10-phenanthroline on chronic liver injury induced by dimethylnitrosamine or ethionine in rats

Although 1, 10-phenanthroline (1, 10-P, 2 mg/100 g) prevents acute liver injury induced by dimethylnitrosamine (DMN), it does not protect female rats against liver damage caused by chronic treatment with DMN (2 mg/ 100 g). Liver damage was ascertained by measuring distribution and total activity of β-glucuronidase, rate of collagen synthesis, total collagen content of the liver, and amount of isocitric dehydrogenase (ICDH) in the serum. However, after simultaneous treatment with 1, 10-P and DMN for three weeks, the total amount of noncollagenous liver proteins and of microsomal protein and aniline hydroxylase activity were higher than in livers of rats receiving DMN alone. The proliferation of the smooth endoplasmic reticulum in livers of dogs treated for a 14-week period with 1, 10-P was demonstrated by ultrastructural techniques. Chronic liver injury induced by feeding female rats with a 0.3% d, 1-ethionine diet for five weeks was prevented by simultaneous administration of 1, 10-P (2 mg/100 g, i.p. 3 times weekly). It is suggested that when administered chronically, 1, 10-P acts as an inducer of the liver microsomal system and therefore increases the activity of liver mixed-function oxidases. This explains why chronic administration of 1, 10-P does not protect rats against injury caused by DMN. Ethionine hepatotoxicity, which does not seem to be related to the microsomal activity, is substantially decreased by as yet unknown mechanisms.