Involvement of mitochondrial dysfunction in hepatotoxicity induced by Ageratina adenophora in mice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ageratina adenophora is a noxious plant and it is known to cause acute asthma, diarrhea, depilation, and even death in livestock (Zhu et al., 2007; Wang et al., 2017). A. adenophora grows near roadsides and degraded land worldwide (He et al., 2015b). In the areas where it grows, A. adenophora is an invasive species that inhibits the growth of local plants and causes poisoning in animals that come in contact with it (Nie et al., 2012). In China, these plants can be found in Yunnan, Sichuan, Guizhou, Chongqing, and other southwestern areas (He et al., 2015a) and they have become a dominant species in these local regions. It threatens the native biodiversity and ecosystem in the invaded areas and causes serious economic losses (Wang et al., 2017). It has been reported that A. adenophora can grow in the northeast direction at a speed of 20 km per year in China (Guo et al., 2009). Because of the damage caused by A. adenophora, it ranks among the earliest alien invasive plant species in China (Wang et al., 2017).

Mollusc C-reactive protein crosses species barrier and reverses hepatotoxicity of lead in rodent models.

Achatina fulica C-reactive protein (ACRP) reversed the toxic effects of lead nitrate both in vivo in mice and in vitro in rat hepatocytes restoring the basal level of cell viability, lipid peroxidation, reduced glutathione and superoxides. Cytotoxicity was also significantly ameliorated in rat hepatocytes by in vitro pre-treatments with individual subunits (60, 62, 90 and 110 kDa) of ACRP. Annexin V-Cy3/CFDA dual staining showed significant reduction in the number of apoptotic hepatocytes pre-treated with ACRP. ACRP induced restoration of mitochondrial membrane potential was remarkable. ACRP pre-treatment prevented Pb-induced apoptosis mediated by caspase activation. The antagonistic effect of ACRP may be due to scavenging of reactive oxygen species which maintained the homeostasis of cellular redox potential as well as reduced glutathione status. The results suggest that ACRP crosses the species barrier and it may be utilized as a viable exogenous agent of cytoprotection against heavy metal related toxicity.

Efeito protetor de antagonista das gliproteínas IIb/IIa nas alterações hepáticas e pulmonares secundárias à isquemia e reperfusão do fígado em ratos / Protective effects of an inhibitor of glycoprotein IIb/IIIa in the hepatic and pulmonary disturbances secondary to ischemia and reperfusion injury of rat’s liver

RACIONAL: A lesão de isquemia e reperfusão hepática é um evento comum e responsável por considerável morbidade e mortalidade. OBJETIVO: Avaliar efeitos de inibidor da glicoproteína IIb/IIIa, cloridrato de tirofiban, nas alterações hepáticas e pulmonares da lesão de isquemia e reperfusão de fígado de ratos. MÉTODO: Vinte e três ratos Wistar divididos em três grupos: laparotomia (n = 6), isquemia e reperfusão que receberam solução fisiológica (n = 8), e submetidos a isquemia e reperfusão e tratados com o cloridrato de tirofiban (n = 9). Foram realizadas dosagens das aminotransferases e análise histológica hepática. Avaliação pulmonar foi realizada pelo teste do azul de Evans e pela dosagem tecidual da mieloperoxidase no parênquima pulmonar. A oxidação e fosforilação mitocondrial das células hepáticas também foram avaliadas. RESULTADOS: O grupo tratado com cloridrato de tirofiban apresentou menores níveis de aminotransferases, assim como alterações histológicas menos intensas. Avaliação pulmonar demonstrou diminuição no teste de azul de Evans no grupo tratado com cloridrato de tirofiban. Grupo tratado com cloridrato de tirofiban apresentou aumento significativo do estado 3 da respiração mitocondrial e das relações adenosina difosfato utilizado para fosforilação sobre o oxigênio consumido na reação e de coeficiente respiratório. CONCLUSÕES: O uso do cloridrato de tirofiban exerceu papel protetor da lesão hepática de isquemia e reperfusão e impediu o aumento da permeabilidade vascular secundária à lesão de reperfusão hepática.

BACKGROUND Hepatic ischemia-reperfusion injury is responsible for a considerable morbidity and mortality. Aim - To evaluate the effect of a platelet glycoprotein IIb/IIIa receptor inhibitor (tirofiban) on hepatic and pulmonary disturbances associated with hepatic ischemia-reperfusion injury. METHODS: Twenty-three Wistar rats divided in three groups: rats sham-operated (n = 6), rats submitted to ischemia-reperfusion that received saline solution (n = 8), and rats submitted to ischemia-reperfusion treated with 0.7 mg/kg of tirofiban (n = 9). Serum aminotransferases (AST and ALT) were also determined, and the study of hepatic tissue histology was carried out. The evaluation of the pulmonary disturbances was done using the Evans blue test and the tissular determination of myeloperoxidase. Hepatic mitochondrial oxidation and phosphorylation were also measured. RESULTS: There was an increase in the state 3 respiration, ADP/O ratio and respiration control rate in the group treated with tirofiban. This group had also lower levels of aminotransferases and the histological findings were significantly less intense. Pulmonary evaluation demonstrated decrease of the Evans blue test in the tirofiban group and an increase of its tissular determination of myeloperoxidase. CONCLUSION: The inhibition of glycoprotein IIb/IIIa receptor with tirofiban protected the hepatic disturbances and prevented the increase of pulmonary vascular permeability secondary to the ischemia-reperfusion injury of the liver.

Nonalcoholic steatohepatitis--a histological perspective.

Nonalcoholic Steatohepatitis (NASH) is a progressive liver disease that has gained recognition in the last two decades. It may even account for some of the cases previously diagnosed as cryptogenic cirrhosis. Association of this entity,with obesity, insulin resistance and type II diabetes is well documented. In this review we clarify the terminology and describe the histological features associated with NASH. Criteria for diagnosis, grading and staging systems and role of liver biopsy is also discussed.

Mitochondrial hepatopathies.

Hepatocyte mitochondrion functions as a cause and as a target of liver injury. Since the mitochondria are under dual control of nuclear DNA and mitochondrial DNA (mtDNA), mutations in genes of both classes have been associated with inherited mitochondrial hepatopathies. Point mutations, deletions, insertions, rearrangements, DNA depletion--all have been identified. Many factors influence the prevalence of mitochondrial disorders, including the mutations rate, inheritance pattern, population structure, and the genetic background. In primary disorders, mitochondrial defect is the primary cause of liver disease often producing fatal hepatic failure in infancy or childhood. In secondary disorders, insult to mitochondria is caused by either a gene defect that affects non-mitochondrial proteins or by an exogenous injury to mitochondria. Diagnosis should be suspected in cases of liver disease with neuromuscular symptoms, multisystem involvement that cannot be explained by a single pathology or rapidly progressive liver failure in early childhood. Laboratory findings in the blood and urine show an altered redox status. Various antioxidants, vitamins, cofactors, and electron acceptors have been for proposed but none is effective. Presence of neuromuscular or extraintestinal involvement in primary disorder precludes the use of liver transplantation.

Study on ultra-structural pathological changes of rats poisoned by tetramine / 法医学杂志

OBJECTIVE@#To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism.@*METHODS@#Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination.@*RESULTS@#The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells.@*CONCLUSION@#The toxic target organs of tetramine are the heart, brain and liver.

Experimental pathological study of subacute intoxication by Dioscorea bulbifera L / 法医学杂志

OBJECTIVE@#To study the pathological change and the toxic mechanism of Dioscorea bulbifera L in mice.@*METHODS@#Sixty ICR mice were randomly assigned to four groups poisoned respectively with 200% Dioscorea bulbifera L of 1/4 LD50, 1/10LD50, 1/30LD50 and a control group treated with distilled water by oral administration. All animals were pathologically examined with LM and some of them were examined with TEM when the mice died during the experiment or the survival mice were sacrificed after thirty days.@*RESULTS@#The pathological changes showed fatty change and the increasing glycogen of liver cells; degeneration and necrosis of the epithelia of uriniferous tubules. The serum BUN and ALT of the experimental groups mice were higher than that of control group. Enzyme histochemical staining showed the decreasing activity of G-6-P and SDH in the liver cells in the experimental groups.@*CONCLUSION@#The experiment suggests that the target organs were liver and kidney. The toxic mechanism of Dioscorea bublifera L was the damage of the mitochondrional and endoplasmic reticulum membrane directly. As a result, the activity of the SDH and G-6-P decreased, the metabolism was affected.

Lesäo hepatica na insuficiência renal mioglobinurica (rabdomiolise): estudo experimental em ratos / Hepatic dysfunction in myoglobinuric acute renal failure: experimental study in rats

A possivel relaçäo causal entre insuficiência renal mioglobinurica (rabdomiolise) e lesäo hepatica ainda nao esta bem definida e foi objeto deste estudo. Ratos machos (220-270 g) foram privados de agua por 24 horas e divididos em dois grupos: GI-animais experimentais em que a rabdomiolise foi induzida mediante injeçäo intramuscular de glicerol a 50 por cento na dose de 10 ml/kg. GII-animais controles que receberam injecao intramuscular de solucao salina. Vinte e quatro horas apos a injecao todos os animais foram sacrificados. No sangue colhido foram dosados AST, ALT, CK, ureia e creatinina. Os figados foram removidos para estudo histologico e para avaliacao da funcao mitocondrial, determinada polarograficamente com eletrodo de Clark, medindo-se o consumo de oxigenio na ausencia de ADP (S4-Basal) e na presenca de ADP (S3-Ativado). A razao do controle respiratorio (RCR) e relacao ADP/O foram calculadas...