Ultrastructural Changes In Liver Research Articles

Ultrastructural alterations produced in cockerels after mercuric chloride toxicity and subsequent interaction with an organophosphate insecticide.

Ultrastructural changes of liver and kidneys of cockerels exposed to mercuric chloride and subsequent interaction with methylobromofenvinphos (IPO 63 compound) were studied. Group A birds were treated for 4 weeks with 300 ppm mercuric chloride in drinking water; Group B birds were treated for 4 weeks with mercuric chloride followed by single oral dose of 240 mg/kg of IPO 63; Group C 240 mg/kg IPO 63 only; and Group D, unexposed controls. Hepatocytes of mercury-IPO 63 interaction group B showed large lysosomes containing myelin bodies, swollen mitochondria with cristeolysis, dilated endoplasmic reticulum and numerous vacuoles containing granular material. Mercury-intoxicated birds showed similar but less severe changes, whereas IPO 63-treated birds showed accumulation of glycogen granules, fat droplets, and few lysosomal bodies as well as other changes. Renal corpuscles of kidney from mercury-IPO 63 interaction birds revealed minor ultrastructural changes as vacuolation, swollen mitochondria of podocytes and slight thickening of the glomerular basement membrane. Proximal tubular cells showed extreme damage such as, microvillar loss, dilation of endoplasmic reticulum, accumulation of lysosomal bodies, glycogen granules, myelin figures, swollen mitochondria with granular material, numerous vacuoles containing degenerated membranous organelles and distorted, pyknotic nucleus with marked dilation of nuclear membrane. Mercury intoxicated birds showed similar but less pronounced changes in tubules. These observations suggest that the effect of mercuric chloride toxicity and then interaction with an organophosphorus insecticide causes extreme damage to hepatic and renal cells that appears to be additive.

Tissue drug accumulation and ultrastructural changes during amiodarone administration in rats

Pulmonary and hepatotoxicity are the two major side effects of chronic amiodarone therapy. We studied the accumulation of amiodarone and its principal metabolite, desethylamiodarone, in lung and liver of rats treated ip for 21 to 23 days with either 40 or 80 mg/kg/day amiodarone. The ultrastructural changes in liver, lung, and alveolar macrophages in saline controls and in rats on the two amiodarone dosage regimens were investigated. There was a dose-dependent increase in amiodarone and desethylamiodarone levels in serum and in tissues. The desethylamiodarone/amiodarone ratios in liver and lung, but not in serum, increased significantly with increasing dose. Serum also contained another metabolite, monodeiodinated desethylamiodarone. Increase in vacuolization and presence of whorled lamellar inclusion bodies in alveolar macrophages occurred with an increase in dose and higher lung amiodarone and desethylamiodarone levels. Electron microscopy of the liver of amiodarone-treated rats revealed the presence of large inclusion bodies partially filled with amorphous material in the cytoplasm. The quantitative relationship of the above changes to organ toxicity and to phospholipidosis that accompanies amiodarone administration remains to be established.

Glutathione synthesis and export in experimental liver cirrhosis induced by thioacetamide: Relations to ultrastructural changes

Micro-and macronodular experimental liver cirrhosis was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months, respectively. The glutathione (GSH) status (content, synthesis, export) and ultrastructural changes of liver were investigated 14 d after withdrawal of TAA. The hepatic level of GSH was increased after 6 months TAA treatment. The levels of oxidized glutathione (GSSG) were not changed after 3 months or 6 months TAA administration. The GSH synthesis was not disturbed in the cirrhotic livers; only the ratio between the 2 synthesizing enzymes was changed in macronodular liver cirrhosis. The plasma GSH content was reduced in both cases, independent of the stage of liver cirrhosis. The electron microscopic studies on cirrhotic rat livers revealed a series of characteristic structural changes, such as disorganization and total lack of the microvilli border, appearance of basement membrane-like deposits within the narrowed space of Disse, disappearance of the highly porous endothelial cell lining and partly an intensively detoriated blood supply within the pseudolobules. It is suggested that all these changes may contribute to a disturbance of the GSH export from the hepatocytes into the blood. It is very likely, however, that the alterations of the sinusoidal cell surface play the most important role. 1. The GSH/GSSG redox potential is shifted in favour of the reduced form in this cirrhosis model. This shift seems to be connected with later stages of cirrhogenesis. 2. A GSH export disturbance is responsible for the decreased plasma GSH level in liver cirrhosis.

Tissue Drug Accumulation and Ultrastructural Changes during Amiodarone Administration in Rats

Pulmonary and hepatotoxicity arc the two major side effects of chronic amiodarone therapy. We studied the accumulation of amiodarone and its principal metabolite, desethylamiodarone, in lung and liver of rats treated ip for 21 to 23 days with either 40 or 80 mg/kg/day amiodarone. The ultrastructural changes in liver, lung, and alveolar macro-phages in saline controls and in rats on the two amiodarone dosage regimens were investigated. There was a dose-dependent increase in amiodarone and desethylamiodarone levels in serum and in tissues. The desethylamiodarone/amiodarone ratios in liver and lung, but not in serum, increased significantly with increasing dose. Serum also contained another metabolite, mono-deiodinated desethylamiodarone. Increase in vacuolization and presence of whorled lamellar inclusion bodies in alveolar macrophages occurred with an increase in dose and higher lung amiodarone and desethylamiodarone levels. Electron microscopy of the liver of amiodarone-treated rats revealed the presence of large inclusion bodies partially filled with amorphous material in the cytoplasm. The quantitative relationship of the above changes to organ toxicity and to phospholipidosis that accompanies amiodarone administration remains to be established.

Ultrastructural changes in liver after the test exposition of laser irradiation.

The aim of this research was to verify characteristic morphological changes in the liver with regard to survival time after laser irradiation. The duration of irradiation was constant. For the purpose of irradiation we used a helium-neon laser. The value of the energy absorbed during the exposition amounted to about 2.5 J. Segments from the irradiated liver field of rats were taken directly after decapitation following different times of survival, and the changes were estimated in an ultrastructural microscope. Our results showed dependence of certain morphological changes (perceptible only by ultrastructural examination) on the time of survival after irradiation.

Monooxygenase activity and ultrastructural changes of liver in the course of chronic exposure of rats to vinyl chloride.

The activity of microsomal cytochrome P-450 monooxygenase and ultrastructure of the liver have been studied in rats exposed dynamically to 50, 500, and 20,000 ppm of vinyl chloride (VC) over 10 months. After 1 and 3 months of exposure to 500 and 20,000 ppm of VC, the level of cytochrome P-450 was slightly lower than in the control animals and upon continuation of exposure it was restored to the original level accompanied by slight increase of activity of aniline p-hydroxylase. Liver enlargement, developed in the course of the exposure, was accompanied by ultrastructural alterations beginning in the 3rd month of exposure to all concentrations of VC. Development of hepatic alterations (hypertrophy of smooth and rough endoplasmic reticulum, swelling of mitochondria, accumulation of lipid droplets, focal cytoplasmic degradation) is discussed with regard to the activity of microsomal monooxygenase system in metabolizing VC to toxic metabolites.

Cadmium and liver pathology: Faeder, E. J., Chaney, S. Q., King, L. C., Hinners, T. A., Bruce, R. & Fowler, B. A. (1977). Biochemical and ultrastructural changes in livers of cadmium-treated rats. Toxic. appl. Pharmac.39, 473

Cadmium and liver pathology: Faeder, E. J., Chaney, S. Q., King, L. C., Hinners, T. A., Bruce, R. & Fowler, B. A. (1977). Biochemical and ultrastructural changes in livers of cadmium-treated rats. Toxic. appl. Pharmac.39, 473

Unusual responses of rat hepatic and renal peroxisomes to RMI 14, 514, a new hypolipidemic agent.

RMI 14, 514 ([5-tetradecycloxy]-2-furancarboxylic acid) represents a new class of hypolipidemic agents which cause unusual ultrastructural changes in liver of male rats and in selected peroxisomal enzymes in liver and kidney of both sexes. Among the principal ultrastructural changes in peroxisomes of male rat liver were (a) cavitation and compartmentalization of the matrix, often giving the appearance of a peroxisome-within-a-peroxisome, and (b) narrow, dense extensions of canaliculi or cisterns from the periphery of the peroxisome, forming partial circlets or surrounding irregular areas of cytoplasm. The unusual enzyme responses were (a) elevation of catalase activity in liver and kidney in female rats, (b) increased activity of three hydrogen peroxide-producing oxidases (urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase) in the liver of both sexes, and (c) elevation of activity of the last two oxidases in male kidney. The peculiar ultrastructural changes in liver peroxisomes combined with the responses of selected peroxisomal enzymes represent unusual modulations or adaptations of these organelles to a hypolipidemic agent, the effects of which have not been reported extensively.

Biochemical and ultrastructural changes in livers of cadmium-treated rats

Groups of male Wistar rats were given 0, 0.25, 0.50, or 0.75 mg of Cd/kg body wt sc 3 days/week for 8 weeks. At the times sampled, the fraction of total cadmium administered in the liver and kidney (40–50% in the liver and 6% in the kidney) remained constant. Until Week 6, no differences were found in plasma aspartate aminotransferase (AAT), γ-glytamyl transpeptidase (GT), and ornithine carbamoyl transferase (OCT) activities. At Week 6, GT and AAT activities became elevated. Small but significant changes in red blood cell carbonic anhydrase activity occurred at 6 and 8 weeks. Electron microscopic examination of liver tissue indicated dilatation of the rough endoplasmic reticulum and prolification of prominent connective tissue fiber bundles at Week 6. These results show a correlation between ultrastructural liver changes and elevations in plasma enzyme activities, which are usually considered to be indicative of chronic liver damage.

3103. Filling in the HCB picture: Koss, G. & Koransky, W. (1975). Studies on the toxicology of hexachlorobenzene. I. Pharmacokinetics. Arch. Tox. 34, 203. Mollenhauer, H. H., Johnson, J. H., Younger, R. L. & Clark, D. E. (1975). Ultrastructural changes in liver of the rat fed hexachlorobenzene. Am. J. vet. Res. 36, 1777.

3103. Filling in the HCB picture: Koss, G. & Koransky, W. (1975). Studies on the toxicology of hexachlorobenzene. I. Pharmacokinetics. Arch. Tox. 34, 203. Mollenhauer, H. H., Johnson, J. H., Younger, R. L. & Clark, D. E. (1975). Ultrastructural changes in liver of the rat fed hexachlorobenzene. Am. J. vet. Res. 36, 1777.

Experimental infection of Aotus monkeys with Plasmodium falciparum Light and electron microscopic changes.

Six splenectomized Aotus owl monkeys were infected with P. falciparum. The animals were sacrificed when they became moribund and tissues were faken for light and electron microscopic studies. Electron microscopy revealed marked structural changes in both the liver and the heart. In the liver there was glycogen depletion, lipid droplet infiltration mitochondrial disorganization with reduction in numbers and alterations of the microvilli in the sinusoidal pole and the bile canaliculi. In the heart, there was lipid droplet infiltration and focal disorganization of the myofibrils around the intercalated disc. There was focal mitochondrial disorganization and mitochondrial concentration around the muscle lesion. The ultrastructural changes in liver and heart were similar to those described in animals dying of shock, of at least two hours duration, in different experimental models. Ultrastructural lesions found in other organs were less marked. In the kidneys there was mainly a moderate lipid infiltration of the tubular epithelium. This change is probably the early precursor of that seen at four hours in animals dying in experimental shock. The above changes are discussed in light of the known pathophysiology of both experimental infections in animals and natural human malarial infections.

Trypanosoma lewisi: ultrastructural changes in rat liver.

Host responses to infection were examined by observing the ultrastructural changes in liver from rats infected withTrypanosoma lewisi from day 1 to day 49 of infection. Trypanosomes were present in large numbers in the sinusoids on the 7th day of infection. By day 14, trypanosomes were seen in kupffer cells. The endoplasmic reticulum showed distended cisternae from day 4 of infection to day 14 of infection. Mitochondria in liver from infected rats increased in number and were swollen only on day 7 of infection. The hepatocytes showed focal areas of lipid from day 7 to day 28 of infection. Residual lysosomes in kupffer cells were found from the 14th to 21st day of infection. Initially, glycogen was dispersed but as the infection advanced, it became aggregated by day 7 of infection. By the 49th day of infection, glycogen again appeared dispersed. At the 35th, 42nd and 49th days of infection, the appearance of the liver was similar in general to that of normal liver.

Electron microscopy of hepatic regeneration

The ultrastructure of regenerating rat liver was studied during the first 4 days after two-thirds partial hepatectomy. It was found that changes occurred rapidly in cytoplasmic fat concentration and that there was pinocytosis of fat granules from plasma, with transport through cisternae of the endoplasmic reticulum and concentration in Golgi vacuoles. The number and electron density of cytosomes increased, and some of the electron density appeared to be lipid which came from Golgi vacuoles. Many of these changes disappeared by 9 hours after hepatectomy. Other non-specific changes, which consisted in swelling and pallor of mitochondria, loss of mitochondrialdense bodies, and wrapping of ergastoplasmic membranes about mitochondria, were observed. There was rapid increase in small granule content of the nucleus, both in the nucleolus and extranucleolar chromatin, beginning at 4 hours and reaching a maximum about 1 day after hepatectomy. These changes rapidly subsided so that, by 4 days after hepatectomy, most liver cells were normal except for decreased glycogen and the presence of cytoplasmic fat in occasional cells. This relative ultrastructural normalcy was somewhat surprising in view of the active proliferation of liver cells for 7–10 days after partial hepatectomy. The finding of striking ultrastructural changes in liver during the first few hours after hepatectomy suggests that investigation of the biochemical and biologic parameters of regeneration soon after hepatectomy might be particularly fruitful. Also, since the ultrastructural changes occur within the first few hours after hepatectomy, the occurrence of a specific circulating stimulus or inhibitor of regeneration would appear unlikely because a long period of time would seem to be required for sufficient change in their concentration to initiate regeneration.