;73:171-3. Galle P, Guidicelli CP, Nebout T. Ultrastructural localisation of aluminium in hepatocytes of hemodialyzed patients. Ann Pathol 1987;7:163-70. Abubakar mg, Taylor A, Ferns GA. Aluminium administration is associated with enhanced hepatic oxidant stress that may be offset by dietary vitamin E in the rat. Int J Exp Pathol 2003;84:49-54.
Milka Bogdanović, Ana Janeva and Petar Bulat
Devoshree Mukherjee and Riaz Ahmad
539 : 565–576. Kumar RNV, Kuttan R. (2000). Inhibition of N′ -nitrosodiethylamine-induced hepatocarcinogenesis by Picroliv. J Exp Clin Canc Res 19 (4): 459–465. Matsui Y, Okuda Y, Nakagawa M, Kwon AH, Minoura T, Hiramatsu Y, Uetsuji S, Kamiyama Y. (1994). Effect of hepatocytes volume on energy status in the cirrhotic rat liver. J Gastroenterol Hepato l 9 : 613–619. Rezai A, Fazlara A, Haghikaramolah M, Shahriari A, Zadeh HN, Pashforosh M. (2013). Effect of Echinacea purpurea on hepatic and renal toxicity induced by diethylnitrosamine in
Nursel Gül, Nuri Yiğit, Fulya Saygılı, Ebru Demirel and Ceren Geniş
We used transmission electron microscopy to examine the cytotoxic effects of the second-generation anticoagulant rodenticides difenacoum and brodifacoum on rat liver. A single dose of difenacoum or brodifacoum was administered to rats by gastric gavage and liver samples were taken after 24 h, four days or seven days. In the livers of rats treated with difenacoum for 24 h, hepatocytes typically showed increased numbers of lysosomes, as well as enlargement of both the perinuclear space and the cisternae of the rough endoplasmic reticulum (RER), while sinusoids were irregularly shaped and contained Kupffer cells. Similar irregularities occurred in brodifacoum-treated rats at the same time point, but additionally increased numbers of vacuoles, damaged mitochondrial cristae, and clumping of chromatin were observed in hepatocytes, and hemolysed erythrocytes were noted in the sinusoids. Comparable findings were made in each group of rats after four days. After seven days of difenacoum treatment, hepatocytes suffered loss of cytoplasmic material and mitochondrial shrinkage, while RER cisternae became discontinuous. In contrast, exposure to brodifacoum for seven days caused the formation of numerous vacuoles and lipid droplets, disordered mitochondrial morphology, chromatin clumping and invagination of the nuclear envelope in hepatocytes. Sinusoids in the livers of rodenticide-treated rats contained an accumulation of dense material, lipid droplets, cells with pycnotic nuclei and hemolysed erythrocytes. Overall, our results show that brodifacoum causes more severe effects in liver cells than difenacoum. Thus our microscopic data along with additional biochemical assays point to a severe effect of rodenticide on vertebrates.
Agnieszka Pedrycz, Zbigniew Boratyński, Piotr Siermontowski, Jacek Mendocha, Marcin Orłowski and Katarzyna Van Damme-Ostapowicz
The aim of this study was to develop and examine a model of apoptosis and necrosis of hepatocytes induced by a damaging factor - adriamycin, correlating time after its administration with cell death type, and to investigate the localisation within the liver acinus of hepatocytes dying in these two ways. The results obtained in the present and previous studies were compared in order to make a map of cell death localisation in the liver acinus, showing the effect of time in action and dose of adriamycin. The experiment was performed on 32 female Wistar rats, divided into four groups: I and II - experimental, and III and IV - control. Adriamycin (3 mg/kg b.w.) was administered intraperitoneally to rats in groups I and II, and the rats were decapitated after four (group I) and eight (group II) weeks. Animals in control groups III and IV were given 0.5 mL of 0.9% NaCl solution, and decapitated after four and eight weeks respectively. Sections of the liver were examined with a three-stage immunohistochemical method. This method allowed to examine hepatocytes qualitatively and quantitatively for the presence of proteins involved in three types of apoptosis: induced by the mitochondrial pathway (caspase 3, 9), the intrinsic pathway related to endoplasmic reticulum stress (caspase 3, 12), and the extrinsic pathway (caspase 3, 8). One of the inflammatory markers, caspase 1, was also examined. The zonal localisation of all three types of apoptosis was assessed in the liver tissue. More oxidated hepatocytes indicated only signs of the internal mitochondrial pathway, whereas less oxidated hepatocytes induced the internal reticular pathway and the external apoptotic pathway. The period between adriamycin administration and hepatic cell investigation was a main factor of the process. A longer period post insult resulted in a more pronounced effect of the activation of apoptosis. Sections explored eight weeks after treatment with different doses of the drug (3 and 5 mg/kg in the previous study) showed a similar intensity of apoptosis.
Brijender Bhushan and Prabhu Narain Saxena
Pesticides are the main remedy for pest eradication, but their use has been found to be harmful also to various non-target organisms. In this study, giant cell formation was observed in hepatocytes of experimental albino rats following two type II pyrethroid pesticdes, Cypermethrin and Beta-cyfluthrin. Histopathological examination was done for this purpose and the results revealed the formation of giant cells and polyploidy condition following intoxication of these experimental compounds with Beta-cyfluthrin, with an edge over, and Cypermethrin, probably due to structural differences.
Xin Sun, Yan Zhang and Meilin Xie
Non-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.
Muhammed Manzoor, Rajesh K. Wadhwa, Zaigham Abbas, Syed Mujahid Hasan, Nasir Hasan Luck and Muhammed Mubarak
Nonalcoholic steatohepatitis (NASH) is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is often a “silent” liver disease. Estimated prevalence of NASH ranges from 3% to 5% in different studies. The prevalence of NASH-related cirrhosis in the general population is not known. Herein, we report a case of a young female presented with NASH-related cirrhosis in the setting of poorly controlled celiac disease (CD) and microscopic colitis. A variety of liver abnormalities have been observed in patients with CD, but this unique constellation of the gut and liver pathologies has not been reported previously.
Natthaporn Tanpowpong and Teerasak Phewplung
Background: Gadolinium diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) is a developed agent with preferential uptake by hepatocytes. A rapid and specific hepatocyte uptake with biliary excretion was observed of approximately 50% of the injected dose. The amount of contrast uptake is thought to be related to reserve liver function.
Objectives: To evaluate correlation between liver signal intensity in the hepatobiliary phase of Gd-EOB-DTPA and reserved liver function by using the model score for end-stage liver disease (MELD).
Methods:All patients who underwent magnetic resonance (MR) imaging with Gd-EOB-DTPA were retrospectively collected. The patients with serum creatinine level higher than 1.5 mg/dL or patients without available data to estimate MELD score were excluded. Thirty-six patients were enrolled. A signal-to-noise ratio (SNR) in the liver parenchyma on a fat-suppressed three dimensional fast spoiled-gradient recalled echo sequence images before and 20 minutes after contrast injection were measured and calculated on PACS by two radiologists. The MELD score was determined and interobserver reliability was estimated.
Results: Among 36 patients, we found a negative relationship between the percentage enhancement and the MELD score (P < 0.01, r = 0.545). The SNR at 20 minutes after Gd-EOB-DTPA injection also had a negative relationship with the MELD score with statistical significance (P < 0.01, r = 0.460). Interobserver reliability was 0.675.
Conclusion: The percentage enhancement in hepatobiliary phase of Gd-EOB-DTPA can predict reserved liver function.
Yesilmen Simten, Yaman Turan, Sağsöz Hakan and Bademkiran Servet
Brucellosis and Q fever, two zoonoses, are important causes of abortion in ruminants, as well as economically significant diseases caused by a gram-negative bacterium. Determination of these diseases is therefore of great importance. In this study, the organs of 35 naturally infected and aborted ovine fetuses were examined for the presence of changes resulting from infections by Brucella melitensis and Coxiella burnetii, according to macroscopic, bacteriological, histopathological and immunohistochemical methods. B. melitensis was observed in 21 cases, and C. burnetii was observed in 8 cases of the aborted ovine fetuses, and these were determined with immunohistochemical methods. Brucellosis was observed in 18 of the aborted ovine fetuses, and this was determined by microbiological methods. Negative (-) results were found for all of the other fetuses. The Brucella antigen was determined to be localized as intracytoplasmic in mainly alveolar macrophages, bronchi, bronchioles, glandular epithelial cells around bronchial glands, neutrophils, hepatocytes and Kupffer cells. The Coxiella antigen was found to be localized in the alveolar macrophages in the lungs, bronchi, bronchioles and alveolus, and in the cytoplasms of bronchial gland epithelial cells, and in the cytoplasms of hepatocytes and Kupffer cells in the liver. Immunohistochemical and microbiological diagnoses of brucellosis and coxiellosis were compared; it was concluded that immunohistochemical methods were more safely applied than microbiological methods.
Natalia Motorna, Svetlana Rybalko, Tatyana Kvitnitskaya-Ryzhova, Daria Starosyla, Iryna Strokina, Rostyslav Kaminsky, Sergey Savosko, Liudmyla Sokurenko and Yuri Chaikovsky
The study of herpetic infection is a topical problem. Although the peculiarities and consequences of acute HSV-I infection in the brain are quite well-studied, little is known about the damage to other organs which are not a source of latent HSV-I infection, the liver in particular. The current study is aimed at determining the ultrastructural changes in murine liver following HSV infection and stroke. Liver samples obtained from four groups of animals were studied: 1) intact mice; 2) mice with stroke; 3) mice infected with HSV-I; 4) mice aflicted with HSV-I and subsequently simulated stroke. The study showed the reproduction of the virus in hepatic endotheliocytes, although no virions were detected in the hepatocytes. Therefore, the described changes were considered the consequences of the infectious process. Pathological changes of hepatocytes consisted of deformation and fragmentation of the nuclei, as well as accumulation of osmiophilic granules, lysosomes and lamellary bodies. Latent HSV-I infection may reactivate in liver after the stroke, potentially causing the complications of the underlying disease.