Morphological alterations and focal deficiency of the histochemical activity of acid and alkaline nucleases in rat liver after chronic administration of phenobarbital

1977 ◽  
Vol 161 (4) ◽  
pp. 363-375 ◽  
Author(s):  
L. Fort ◽  
H.S. Taper ◽  
J.M. Brucher
1962 ◽  
Vol 202 (2) ◽  
pp. 343-346 ◽  
Author(s):  
Dennis D. Goetsch ◽  
L. E. McDonald

The effects of glucocorticoid administration on oxygen uptake, glucose and glycogen disappearance, lactic acid formation, and inorganic phosphate and protein levels in rat liver homogenates have been studied. A single injection of hydrocortisone, prednisolone, or 9 α-fluoroprednisolone 5 hr before sacrifice resulted in a highly significant increase in oxygen uptake by rat liver homogenates, whereas chronic administration of prednisolone daily for 7 days caused a marked inhibition in homogenate respiration. Glycolytic rate did not appear to be affected by single injections since endogenous carbohydrate utilization was similar in liver homogenates prepared from control and treated animals. Incubation of liver homogenates under aerobic conditions disclosed that inorganic phosphate levels were decreased in homogenates from corticoid-treated rats, whereas these levels were similar in treated and control liver homogenates incubated under nitrogen. Under anaerobic conditions, liver homogenates from treated rats accumulated lactic acid more rapidly than untreated liver homogenates. Glucocorticoid treatment did not appear to affect protein disappearance since no differences between protein levels in treated and untreated rat liver homogenates were detected following incubation.


Author(s):  
Erika Randerath ◽  
Kurt Randerath ◽  
Ranjani Reddy ◽  
Tracy F. Danna ◽  
M. Sambasiva Rao ◽  
...  

1989 ◽  
Vol 17 (4_part_2) ◽  
pp. 782-788 ◽  
Author(s):  
Stephen K. Durham ◽  
Abraham Brouwer

Recent results (3) indicate that 200 mg 3,4,3′,4′-tetrachlorobiphenyl induces hepatomegaly accompanied by significant decreases in serum and hepatic retinoid content and hepatocyte morphologic alterations of proliferated and vesiculated endoplasmic reticulum and megamitochondria with paracrystalline inclusions. There was also an associated change in the number, size, and distribution of lipid droplets in hepatocytes and fat-storing cells. Electron microscopic autoradiographic techniques were utilized to determine the cellular and subcellular distribution of 3H-3,4,3′,4′-tetrachlorobiphenyl (3H-TCB) in the adult rat liver and determine if there is any relationship between subcellular morphologic change and radiolabel localization. Adult female WAG/Rij rats received a single intraperitoneal injection of 200 mg TCB/kg containing 1.85 mCi of 3H-TCB and were sacrificed at 1, 3, 7, and 14 days following exposure. The vast majority of 3H-TCB-derived radioactivity was located in the hepatocyte at all time points examined, ranging from 79–86% of the total number of autoradiographic grains counted over the liver cells. Sequential order of radiolabel localization per liver cell type at 1, 3, and 7 days was hepatocyte > > > Kupffer cell > fat-storing cell > endothelial cell. At day 14, the sequential order of radiolabel localization per liver cell type was hepatocyte > > > fat-storing cell > Kupffer cell > endothelial cell, which indicates that there was some shift movement of label over time. The lipid droplet, mitochondria, and endoplasmic reticulum were the subcellular structures or organelles of hepatocytes having the highest number of 3H-TCB-derived grains at all time periods examined. The predominant morphological alterations induced following TCB intoxication were observed in these organelles. The results of this study suggests that there is an association between TCB localization and morphologic change induced in mitochondria and endoplasmic reticulum of hepatocytes following TCB exposure.


1992 ◽  
Vol 11 (2) ◽  
pp. 233-248 ◽  
Author(s):  
E.J. Sinkeldam ◽  
V.M.H. Hollanders ◽  
R.A. Woutersen ◽  
H.B.W.M. Koëter ◽  
A. Bär

Lactitol is a disaccharide sugar alcohol (polyol) which holds promise as a reduced calorie, noncariogenic sugar substitute. In a multigeneration reproduction study, lactitol was fed to Wistar-derived Cpb:WU rats of both sexes throughout three successive generations at dietary concentrations of 0, 2, 5, and 10%. A comparison group receiving a diet with 20% lactose was included during the F., generation. The initial mating comprised 20 male and 40 female rats per group. For subsequent matings, 10 males and 20 females were used. In each generation, two litters were reared until they were at least 3 weeks old. Fertility was uniformly high in all treatment groups throughout the study and the feeding of lactitol was not associated with any adverse effects on fertility and reproductive performance. However, growth rates and survival were slightly decreased in pups of the 10% lactitol group, except in F3 litters where no effect of lactitol on survival was seen. In the 20% lactose group of the F, generation, a similar growth retardation and decreased survival was seen. The second litter of third-generation rats (F3b) was subjected to gross and histopathological examination 4 weeks after weaning. F3b rats fed 5 or 10% lactitol showed cecal enlargement which was not associated with any morphological alterations and which is commonly seen in rodents fed polyols or slowly digestible carbohydrates. In some F3b males of all dosage groups, an opaque appearance of the liver cell cytoplasm was noted. However, this effect was not dose related and was not accompanied by any other hepatic changes in the lactitol groups. Since this phenomenon was not seen in older rats or after chronic administration of lactitol, it was considered to be a transient manifestation of an altered metabolism in young rats. All other histopathological findings were equally distributed between control and test animals, or occurred in one or a few rats only. It is concluded that lactitol administered in the diet to three successive generations of rats at levels up to 10%, has no adverse effects on reproductive performance in either sex. The slight developmental delay which occurred in some generations, has been observed earlier with other polyols and may be attributed to the poor digestibility of these compounds.


2011 ◽  
Vol 6 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Yoshinori Muto ◽  
Yumiko Tanabe ◽  
Kiyoshi Kawai ◽  
Yukio Okano ◽  
Hideo Iio

AbstractClimacostol is a resorcinol derivative that is produced by the ciliate Climacostomum virens. Exposure to purified climacostol results in lethal damage to the predatory ciliate Dileptus margaritifer and several other ciliates. To elucidate the mechanism of climacostol toxic action, we have investigated the effects of this compound on the swimming behavior of Tetrahymena thermophila and the respiratory system of isolated rat liver mitochondria. When added to living T. thermophila cells, climacostol markedly increased the turning frequency that was accompanied by a decrease in swimming velocity and subsequently by cell death. Observations by DIC and fluorescence microscopy showed morphological alterations in climacostol treated T. thermophila, indicating that climacostol might exert cytotoxic action on this organism. In the experiment with isolated rat liver mitochondria, climacostol was found to inhibit the NAD-linked respiration, but had no apparent effect on succinate-linked respiration. This finding indicates that climacostol specifically inhibits respiratory chain complex I in mitochondria. The combination of results suggest that the inhibition of mitochondrial respiration may be the cytotoxic mechanism of climacostol’s defenses against predatory protozoa.


Author(s):  
Moustafa Mohamad ◽  
Richard L. Drake ◽  
Robert R. Cardell

Chronic administration of phenobarbital, an anticonvulsant drug, or rifampicin, an antituberculous drug, alters hepatocyte ultrastructure by inducing the proliferation of smooth endoplasmic reticulum (SER) and changes in glycogen content. While these generalized effects are important, the lobular location of hepatocytes must be considered since pericentral and periportal hepatocytes differ morphologically and most hepatotoxic compounds affect specific zones of the liver. We treated adult male rats with phenobarbital or rifampicin for 5 days to evaluate the effect of each drug on hepatic glycogen levels, glycogen distribution across the liver lobule, and hepatocyte ultrastructure, especially the SER. Our results show a decrease in hepatic glycogen levels as determined biochemically in both treatment groups. Semithin sections of liver specifically stained for glycogen (Figs. 1-3) show that in treated animals glycogen in pericentral and periportal hepatocytes is reduced (Figs. 2,3). Ultrastructurally, periportal hepatocytes typically have clumped glycogen (Fig. 4); however, in treated animals periportal hepatocytes that show the greatest reduction of glycogen contain extensive SER (Fig. 5).


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