Ultrastructural Changes In Liver Cells Research Articles

Citrinin-Induced Hepatotoxicity in Mice Is Regulated by the Ca2+/Endoplasmic Reticulum Stress Signaling Pathway.

Citrinin (CTN) is a mycotoxin found in crops and agricultural products and poses a serious threat to human and animal health. The aim of this study is to investigate the hepatotoxicity of CTN in mice and analyze its mechanisms from Ca2+-dependent endoplasmic reticulum (ER) stress perspective. We showed that CTN induced histopathological damage, caused ultrastructural changes in liver cells, and induced abnormal values of biochemical laboratory tests of some liver functions in mice. Treatment with CTN could induce nitric oxide (NO), malondialdehyde (MDA), and reactive oxygen species (ROS) accumulation in mice, accompanied with losses of activities of superoxide dismutase (SOD) and catalase (CAT), levels of glutathione (GSH), and capacities of total antioxidant (T-AOC), resulting in oxidative stress in mice. Furthermore, CTN treatment significantly increased Ca2+ accumulation, upregulated protein expressions of ER stress-mediated apoptosis signal protein (glucose regulated protein 78 (GRP78/BIP), C/EBP-homologous protein (CHOP), Caspase-12, and Caspase-3), and induced hepatocyte apoptosis. These adverse effects were counteracted by 4-phenylbutyric acid (4-PBA), an ER stress inhibitor. In summary, our results showed a possible underlying molecular mechanism for CTN that induced hepatocyte apoptosis in mice by the regulation of the Ca2+/ER stress signaling pathway.

Genetic and Ultrastructural studies in bone marrow and testis of mice cells under the effect of Glurenor drug

Mutagenetic effects and ultrastructural changes of antidiabetic Glurenor drug were studied in vivo in the highly sensitive micronucleus test. Eight groups of forty male mice used in this study to detect chromosomal abnormalities in somatic and germ cells. Three groups orally administrate therapeutic doses of Glurenor at (30, 60, 120) mg/kg daily the fourth group act as control group. Control group and the treated group with 120 mg/kg were used for ultrastructural examination. While the other four groups were used for bone marrow micronucleus test which receives successive doses of Glurenor as (0.0 & 30) mg/kg for 1, 10 &20 days. A cytogenetic examination of treated and untreated mice showed a significant increase of total chromosomal aberrations (P< 0.01) in both somatic and germ cells at dose 120 mg/kg. when compared by control group. Also Glurenor induced micronucleus polychromatic erythrocytes. Glurenor revealed ultrastructural changes in liver cells represented by deep condensation in the nucleus which revealed by the appearance of a large gap around the nucleus. The condensed chromatin appeared as large sharply marginated electron dense mass that a butted on the nuclear envelope. In addition to electron dark distanced elsewhere (prenuclear), swollen endoplasmic reticulum, Also, observed enlarged nucleolus, and thickening the nuclear membrane. Large vacuoles "hydropic degeneration" also was noticed in the cytoplasm. Our studies had the objective of examining experimentally whether the supposed mutagenic effect of Glurenor can be demonstrated and verified by methods of mutagenicity testing using expermintal mammals. In conclusion, this study revealed that Glurenor gave a positive reaction with a clear dose response in mice. Glurenor gave a mutagenic response from of the chromosomal aberration in somatic and germ cells as well as in micronucleus test. Glurenor showed ultrastructural changes in the liver cells of mice.

Genetic and Ultrastructural studies in bone marrow and testis of mice cells under the effect of Glurenor drug

Mutagenetic effects and ultrastructural changes of antidiabetic Glurenor drug were studied in vivo in the highly sensitive micronucleus test. Eight groups of forty male mice used in this study to detect chromosomal abnormalities in somatic and germ cells. Three groups orally administrate therapeutic doses of Glurenor at (30, 60, 120) mg/kg daily the fourth group act as control group. Control group and the treated group with 120 mg/kg were used for ultrastructural examination. While the other four groups were used for bone marrow micronucleus test which receives successive doses of Glurenor as (0.0 & 30) mg/kg for 1, 10 &20 days. A cytogenetic examination of treated and untreated mice showed a significant increase of total chromosomal aberrations (P< 0.01) in both somatic and germ cells at dose 120 mg/kg. when compared by control group. Also Glurenor induced micronucleus polychromatic erythrocytes. Glurenor revealed ultrastructural changes in liver cells represented by deep condensation in the nucleus which revealed by the appearance of a large gap around the nucleus. The condensed chromatin appeared as large sharply marginated electron dense mass that a butted on the nuclear envelope. In addition to electron dark distanced elsewhere (prenuclear), swollen endoplasmic reticulum, Also, observed enlarged nucleolus, and thickening the nuclear membrane. Large vacuoles hydropic degeneration also was noticed in the cytoplasm. Our studies had the objective of examining experimentally whether the supposed mutagenic effect of Glurenor can be demonstrated and verified by methods of mutagenicity testing using expermintal mammals. In conclusion, this study revealed that Glurenor gave a positive reaction with a clear dose response in mice. Glurenor gave a mutagenic response from of the chromosomal aberration in somatic and germ cells as well as in micronucleus test. Glurenor showed ultrastructural changes in the liver cells of mice.

Lysosomal injury and MFO activity in the liver of flounder ( Platichthys flesus L.) in relation to histopathology of hepatic degeneration and carcinogenesis

Flounder ( Platichthys flesus L.), 18–48 cm total length were sampled in the mouth of the Elbe River during a 3-year interdisciplinary project ‘Fish Diseases in the Wadden Sea’. Lysosomal changes (lysosomal membrane stability) and the activity of biotransforming enzymes (MFOs/EROD) were measured parallel to investigations of ultrastructural changes in liver cells, tissue pathologies and macroscopically visible changes. The aim of the study was to investigate if these cyto- and biochemical parameters were able to reflect contaminant induced biological effects. Interlinking of the results of the MFO activity to the pathological alterations observed at the electron- and light-microscopic levels as well as during macroscopic inspection of identical individuals evidenced that the activity of the biotransformation enzymes (EROD) was not induced in healthy livers, increased considerably with the onset of liver changes and dropped again in those livers with degenerative, preneoplastic and neoplastic lesions. In contrast, concurrent studies of lysosomal membrane stability measured in parallel showed a decrease with the onset and progression of liver lesions from reversible to irreversible, neoplastic change.

Ultrastructural changes in liver cells during severe iron-deficiency anemia

Ultrastructural changes in liver cells during severe iron-deficiency anemia

Metabolic fate of fenitrothion in liver, kidney and brain of rat.

The metabolic fate of fenitrothion, O,O-dimethyl-O-(3-methyl-4-nitro phenyl) phosphorothioate, was investigated in rat tissues during the first 24 hours following the intramuscular administration of the pesticide in the animal. High performance liquid chromatography (HPLC) of the pesticide and its metabolites formed in liver, kidney and brain showed the time-dependent sequential conversion of the pesticide into three major metabolites. These metabolites were separated and purified to homogeneity by HPLC and characterized by IR spectroscopy as O,O-dimethyl-O-)3-methyl-4-aminophenyl) phosphorothioate (metabolite I), O,O-dimethyl phosphorothioate (metabolite II), and O,O-dimethylphosphate (metabolite III). These results indicated reduction of the nitro group in fenitrothion aas the first step, followed by the hydrolytic cleavage of the P-O-aryl bond in metabolite I and the oxidative desulphurylation of metabolite II. Fenitrothion was found to induce ultrastructural changes in liver cells especially after 12 h exposure nuclear membrane was completely distorted, nuclear intactness was totally lost and smooth endoplasmic reticulum and Golgi apparatus were abnormally enlarged. In 24 h, however, the regeneration of the nuclear material was observed.

Transmission and scanning electron microscopic characterization of mouse HEPA 1 hepatoma cells after 2,3,7,8-tetrachloro-para-dibenzodioxin treatment

This work extends previous studies showing ultrastructural changes in liver cells of the intact human or rodent, but little or no change in morphology of hepatoma cells in monolayer culture after treatment with 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) in doses sufficient to elicit marked enzyme induction. Previous work, using the mouse HEPA 1 hepatoma cell in culture, with transmission electron microscopy (TEM), showed only very slight changes, unlike the striking changes seen in in vivo preparations. The present study extends the previous work with HEPA 1 cells by use of scanning electronmicroscopy (SEM) in order to characterize cell surfaces and junctions before and after TCDD. Few if any changes are observed, confirming and extending the previous finding.

Ultrastructural hepatic changes in rats after oral administration of ethoxyquin (EMQ)

A single oral administration (500 mg/kg b.w.) of the antioxidant ethoxyquin (EMQ), was found to result in ultrastructural changes in liver cells, expressed by proliferation of smooth endoplasmic reticulum, dilated cisternae of endoplasmic reticulum, disorganization of mitochondrial membranes and desquamation of lining cells.