Hepatic Sinusoidal Dilatation Research Articles

Role of liver sinusoidal endothelial cell damage in the developmental process of hepatic sinusoidal obstruction syndrome: a focus on the research progress of immune inflammatory mechanisms

Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

Nanoplastics and chrysene pollution: Potential new triggers for nonalcoholic fatty liver disease and hepatitis, insights from juvenile Siniperca chuatsi

Nanopolystyrene (NP) and chrysene (CHR) are ubiquitous contaminants in the natural environment; however, research on their hepatotoxicity and associated adverse effects remains relatively inadequate. The present study aimed to investigate the hepatotoxic effects of NP and/or CHR at environmentally relevant concentrations, as well as the underlying molecular mechanisms, in juvenile Siniperca chuatsi (mandarin fish). After a 21-day exposure period, the livers of exposed S. chuatsi exhibited macrostructural and microstructural damage accompanied by oxidative stress. Importantly, our study provides the first evidence that NP exposure leads to the development of nonalcoholic fatty liver disease (NAFLD) and hepatitis in S. chuatsi. Similarly, CHR exposure has also been found, for the first time, to cause hepatic sinusoidal dilatation (HSD) and hepatitis. Exposure to the combination of NP and CHR alleviated the symptoms of NAFLD, HSD, and hepatitis. Furthermore, our comprehensive multi-omic analysis revealed that the pathogenesis of NP-induced NAFLD was mainly due to induction of the triglyceride synthesis pathway and inhibition of the very-low-density lipoprotein secretion process. CHR induced HSD primarily through a reduction in vasoprotective ability and smooth muscle contractility. Hepatitis was induced by activation of the JAK-STAT/NF-kappa B signaling pathways, which upregulated the expression of inflammation-specific genes. Collectively, results of this study offer novel insight into the multiple hepatotoxicity endpoints of NP and/or CHR exposure at environmentally relevant concentrations in organisms, and highlight the importance of nanoplastic/CHR pollution for liver health.

Histopathological, physiological, and multi-omics insights into the hepatotoxicity mechanism of nanopolystyrene and/or diclofenac in Mylopharyngodon piceus

Nanopolystyrene (NP) and diclofenac (DCF) are common environmental contaminants in the aquatic ecosystem; therefore, the present study aimed to investigate the hepatotoxicity of NP and/or DCF exposure on aquatic organisms and the underlying mechanisms. Juvenile Mylopharyngodon piceus were used as a model organism to study the effects of NP and/or DCF exposure at environmentally relevant concentrations for 21 days. Subchronic exposure to NP and/or DCF resulted in liver histological damage. In the NP group, the presence of large lipid droplets was observed, whereas the DCF group exhibited marked hepatic sinusoidal dilatation accompanied by inflammation. Additionally, this exposure induced liver oxidative stress, as evidenced by the changes in several physiological parameters, including catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), reactive oxygen species (ROS), and malondialdehyde (MDA). Integrated transcriptomic and metabolomic analysis was performed to further investigate the molecular mechanism underlying hepatotoxicity. Multi-omics analysis demonstrated, for the first time to our knowledge, that NP induced hepatic steatosis mainly through activating the glycerol-3-phosphate pathway and inhibiting VLDL assembly by targeting several key enzyme genes including GPAT, DGAT, ACSL, APOB, and MTTP. Furthermore, NP exposure disrupted arachidonic acid metabolism, which induced the release of inflammatory factors and inhibited the release of anti-inflammatory factors, ultimately causing liver inflammation in M. piceus. In contrast, DCF induced interleukin production and downregulated KLF2, causing hepatic sinusoidal dilatation with inflammation in juvenile M. piceus, which is consistent with the finding of JAK–STAT signaling pathway activation. In addition, the upregulated AMPK signaling pathway in the DCF group suggested perturbation of energy metabolism. Collectively, these findings provide novel insights into the molecular mechanism of the multiple hepatotoxicity endpoints of NP and/or DCF exposure in aquatic organisms.

Normothermic Ex Vivo Liver Machine Perfusion in Mouse.

This protocol presents an optimized erythrocytes-free NEVLP system using mouse livers. Ex vivo preservation of mouse livers was achieved by employing modified cannulas and techniques adapted from conventional commercial ex vivo perfusion equipment. The system was utilized to evaluate the preservation outcomes following 12 h of perfusion. C57BL/6J mice served as liver donors, and the livers were explanted by cannulating the portal vein (PV) and bile duct (BD), and subsequently flushing the organ with warm (37 °C) heparinized saline. Then, the explanted livers were transferred to the perfusion chamber and subjected to normothermic oxygenated machine perfusion (NEVLP). Inlet and outlet perfusate samples were collected at 3 h intervals for perfusate analysis. Upon completion of the perfusion, liver samples were obtained for histological analysis, with morphological integrity assessed using modified Suzuki-Score through Hematoxylin-Eosin (HE) staining. The optimization experiments yielded the following findings: (1) mice weighing over 30 g were deemed more suitable for the experiment due to the larger size of their bile duct (BD). (2) a 2 Fr (outer diameter = 0.66 mm) polyurethane cannula was better suited for cannulating the portal vein (PV) when compared to a polypropylene cannula. This was attributed to the polyurethane material's enhanced grip, resulting in reduced catheter slippage during the transfer from the body to the organ chamber. (3) for cannulation of the bile duct (BD), a 1 Fr (outer diameter = 0.33 mm) polyurethane cannula was found to be more effective compared to the polypropylene UT - 03 (outer diameter = 0.30 mm) cannula. With this optimized protocol, mouse livers were successfully preserved for a duration of 12 h without significant impact on the histological structure. Hematoxylin-Eosin (HE) staining revealed a well-preserved morphological architecture of the liver, characterized by predominantly viable hepatocytes with clearly visible nuclei and mild dilation of hepatic sinusoids.

A unique presentation of peliosis hepatis: A case report and comprehensive review of the literature

Introduction: Peliosis hepatis (PH) is a rare benign vascular condition characterized by dilatation of hepatic sinusoids with occasional involvement of other organs. While associated with chronic immunosuppression, anabolic steroid use, oral contraceptive (OCP) use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and infection with Bartonella, most PH patients are asymptomatic and, thus, identified incidentally. Compromised liver function is sometimes evident through laboratory tests; however, mortality results from cyst rupture and hemorrhage spontaneously or during surgical procedures. Case Report: We report a case of PH identified in a 33-year-old Black female radiologically evaluated for abnormal liver function tests. Computed tomography (CT) revealed enhancement of >100 lesions throughout both liver lobes; a CT-guided biopsy revealed mild macrovesicular steatosis and marked sinusoidal dilation, consistent with peliosis hepatis. Conclusion: We also present a comprehensive literature review describing the associated conditions, pathology, diagnostic methods, and treatment options for PH patients.

Cypermethrin induced liver oxidative DNA damage via the JNK/c-Jun pathway

To clarify the adverse effect of cypermethrin(CYP) on the liver and explore the underlying role of the MAPK pathway. Twenty-four Sprague-Dawley(SD) rats were exposed to 0, 5, 10 and 20 mg/(kg·d) β-CYP by gavage for 31 days. Histomorphological and ultrastructural changes were evaluated by the hematoxylin & eosin(HE) staining and transmission electron microscope(TEM). Levels of MDA and 8-OHdG were detected by ELISA. Expressions of p-JNK and γ-H2A. X were assessed by IHC and IF respectively. RT-PCR was performed to examine mRNA levels of GPx1, GPx4, SOD1, and SOD2 in rat testes. Western blot was conducted to determine protein expressions of GPx1, SOD2, CAT, γ-H2A. X, and the MAPK pathway-associated proteins in rat testes. After β-CYP exposure, the histomorphology and ultrastructures of rat livers were abnormally altered, as evidenced by hepatic sinusoidal dilation, hepatic plate space formation, mitochondrial crest fracture, etc. Moreover, β-CYP induced mRNA levels of GPx1, GPx4, SOD1 and SOD2, as well as protein expressions of GPx1 and SOD2 in the liver. Compared to the control, GPx1 and SOD2 protein expressions were decreased by 57.9% and 50.0%(P<0.05), whereas the MDA level was increased by 56.2%(P<0.05) in the high-dose group. Additionally, the JNK/c-Jun pathway, one of MAPK pathways, in the liver was activated by β-CYP, as shown by the increase of JNK and c-Jun phosphorylation, and protein expressions of p-JNK and p-c-Jun in the high-dose group were elevated by 47.7% and 46.5%(P<0.05) in comparison to the control, but the ERK and p38 pathways were not affected after β-CYP exposure. Furthermore, β-CYP promoted 8-OHdG and γ-H2A. X expressions in the liver. Compared to the control, γ-H2A. X protein expression in the mid-and high-dose group was upregulated by 16.9% and 33.9%(P<0.05), respectively. Cypermethrin had detrimental effects on the liver. CYP not only directly altered liver histomorphology and ultrastructures, but also caused oxidative stress, which activated the JNK/c-Jun pathway, finally inducing the DNA damage.

MRI of Peliosis Hepatis: A Case Series Presentation With a 2022 Systematic Literature Update.

Peliosis hepatis (PH) is a rare benign condition, characterized by hepatic sinusoidal dilatation and blood-filled cystic cavities, often found incidentally, with still challenging diagnosis by imaging due to polymorphic appearance. Based on a retrospective analysis of our series (12 patients) and systematic literature review (1990-2022), to organize data about PH and identify features to improve characterization. Retrospective case series and systematic review. Twelve patients (mean age 48 years, 55% female) with pathology-proven PH and 49 patients (mean age 52 years, 67% female) identified in 33 studies from the literature (1990-2022). 1,5-T; T1-weighted (T1W), T2-weighted (T2W), diffusion-weighted (DW), contrast-enhanced (CE) T1W imaging. We compared our series and literature data in terms of demographic (gender/age/ethnicity), clinical characteristics (symptoms/physical examination/liver test), associated conditions (malignancies/infectious/hematologic/genetic or chronic disorders/drugs or toxic exposure) percentage. On magnetic resonance imaging lesion numbers/shape/mean maximum diameter/location/mass effect/signal intensity were compared. PH pathological type/proposed imaging diagnosis/patient follow-up were also considered. Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports/Series quality assessment. Intraclass correlation and Cohen's kappa coefficients for levels of inter/intrareader agreement in our experience. Patients were mainly asymptomatic (92% vs. 70% in our study and literature) with associated conditions (83% vs. 80%). Lesions showed homogeneous T1W-hypointensity (58% vs. 65%) and T2W-hyperintensity (58% vs. 66%). Heterogeneous nonspecific (25% vs. 51%), centrifugal (34% vs. 8%), or rim-like centripetal (25% vs. 23%) patterns of enhancement were most frequent, with hypointensity on the hepatobiliary phase (HBP), without restricted diffusivity. Good inter- and intrareader agreement was observed in our experience. Concerning JBI Checklist, 19 out of 31 case reports met at least 7 out of 8 criteria, whereas 2 case series fulfilled 5 and 6 out of 10 items respectively. A homogeneous, not well-demarcated T1W-hypointense and T2W-hyperintense mass, with heterogeneous nonspecific or rim-like centripetal or centrifugal pattern of enhancement, and hypointensity on HBP, may be helpful for PH diagnosis. Among associated conditions, malignancies and drug exposures were the most frequent. 4 TECHNICAL EFFICACY: Stage 2.

Polysaccharide of Atractylodes macrocephala Koidz alleviate lipopolysaccharide-induced liver injury in goslings via the p53 and FOXO pathways

Lipopolysaccharide (LPS) can affect the immune system of geese by inducing liver injury. The polysaccharide of Atractylodes macrocephala Koidz (PAMK) have obvious immune-enhancing effects. Accordingly, this experiment investigated the effect of PAMK on LPS-induced liver injury in goslings. Two hundred 1-day-old goslings were randomly divided into the control group, LPS group, PAMK group, and PAMK+ LPS group, and the PAMK and PAMK+ LPS groups were fed the basal diet with 400 mg/kg PAMK, while the control and LPS groups were fed the basal diet. On D 21, 23, and 25 of the formal trial, the goslings in the LPS and PAMK+LPS groups were injected intraperitoneally with 2 mg/kg LPS, and goslings in the control and PAMK groups were injected intraperitoneally with the same amount of saline. Livers were collected on D 25. HE-stained sections showed that PAMK could effectively alleviate the LPS-induced indistinct hepatic cord structure, loss of cytoplasmic contents of hepatocytes, and dilatation of hepatic sinusoids. The biochemical parameters of liver tissues showed that PAMK could alleviate the LPS-induced upregulation of alanine aminotransferase and aspartate aminotransferase. To further investigate the mechanism of the mitigating effect of PAMK on LPS-induced injury, livers from the LPS and PAMK+LPS groups were selected for transcriptome sequencing. The sequencing results showed that there were 406 differentially expressed genes (DEGs) in the livers of LPS and PAMK+LPS goslings, of which 242 upregulated and 164 downregulated. The Kyoto Encyclopedia of Genes and Genome (KEGG) analysis showed that DEGs were significantly enriched in immune signal transduction, cell cycle, and cell metabolism. Besides, protein‒protein interaction analysis showed that 129 DEGs were associated with each other, including 7 DEGs enriched in the p53 and FOXO signaling pathway. In conclusion, PAMK may alleviate LPS-induced liver injury in gosling through the p53 and FOXO signaling pathway. These results provide a basis for further development of PAMK as an immunomodulator.

Effect of long-term manganese exposure on oxidative stress, liver damage and apoptosis in grouper Epinephelus moara ♀ × Epinephelus lanceolatus ♂

Manganese is an indispensable trace element, however, it may be present at high concentrations in water and sediments of aquatic ecosystems due to natural and anthropogenic activities, and can interfere with physiological and biochemical mechanisms in fish. This study was conducted to determine the toxic effects associated with exposure to Mn2+ (0, 0.5, 1, 2, and 4 mg/L) for 30 d, regarding liver damage and apoptosis in Yunlong grouper (Epinephelus moara♀×E. lanceolatus♂). Expression of superoxide dismutase (sod) and catalase (cat) genes in the liver was significantly increased on days 10 and 20 following Mn2+ exposure (4 mg/L), but was reduced on day 30. Similarly, expression of glutathione peroxidase (gpx) and glutathione reductase (gr) genes was elevated after 10 d of exposure to 2 and 4 mg/L Mn2+, but decreased after 20 and 30 d. After 30 d of exposure to high concentrations (2 and 4 mg/L) of Mn2+, liver tissue showed hepatic sinusoidal gap congestion, dilatation, cell vacuolation, and necrosis. In addition, the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) as well as 8-hydroxydeoxyguanosine (8-OHdG) levels were significantly increased after Mn2+ exposure. Moreover, Mn2+ exposure altered the expression pattern of some pivotal genes associated to apoptosis (p53, bax, bcl-2, apaf-1, caspase-9, and caspase-3), which suggested that Mn2+ exposure induces apoptosis through the mitochondrial pathway. The above results showed that excessive Mn2+ induced apoptosis and liver damage in grouper through elicitation of oxidative stress. These insights help elucidate the mechanism by which Mn2+ induces toxicity in marine fish, and provide a new perspective regarding the detrimental effects of heavy metals in fish.

Histopathological changes resulting from the effect of nano-graphene oxide on the liver in laboratory rats

The current study included the use of (48) white male laboratory rats, where the rats were divided into six groups, with 8 rats in each group. The second group with a concentration of 30 mg/kg, the third group with a concentration of 40 mg/kg, the fourth group with a concentration of 50 mg/kg, and the fifth group with a concentration of 60 mg/kg of nano graphene oxide. The sixth group is the control group. The results of the statistical analysis of the study showed a significant decrease in the average body weight. On the last day of the experiment when comparing between the control group and the treated groups, and the results showed a significant decrease in the average liver weight when comparing between the control group and the treated groups. Central vein, hepatic sinusoidal dilatation, hepatocyte nucleus replication, hepatocyte rupture, and nucleolysis As well as thickening of the nuclei in some hepatocytes, infiltration of inflammatory cells, hemorrhage, and dissolution and necrosis of hepatocytes. The results of the over-study by transmission electron microscope also showed changes at the cellular level, represented by the rupture of the nucleus and cytoplasm, in addition to the dissolution of the nucleus.

Salmonella phage CKT1 significantly relieves the body weight loss of chicks by normalizing the abnormal intestinal microbiome caused by hypervirulent Salmonella Pullorum

Pullorum disease caused by Salmonella Pullorum remains an important disease for the poultry industry due to high morbidity and mortality in many countries. Phage therapy is becoming an alternative strategy to control multidrug-resistant Salmonella infections in young chicks. However, how bacteriophages affect the growth performance of chicks infected with S. Pullorum remains poorly understood. Herein, we assessed the therapeutic efficacy of Salmonella phage CKT1 against hypervirulent arthritis-causing S. Pullorum. The results showed that single phage treatment after hypervirulent S. Pullorum infection significantly improved body weight loss of chicks. Compared with enlarged liver and spleen in only Salmonella challenged group, phage administration substantially reduced the liver/body and spleen/body weight ratios, bacterial loads in organs and the degree of hepatic sinusoidal dilatation and congestion. Moreover, phage CKT1 can enter the organs of chicks and stay for at least 3 d in liver and spleen, and promote higher serum levels of IL-6 production within 6 d postinfection, indicating phage-induced bacterial lysis may be involved in inflammatory immune response to S. Pullorum infection. Analysis of the microbiome of gastrointestinal tract of chicks demonstrated that Salmonella challenge significantly reduced the relative abundances of Lachnoclostridium and Blautia, resulting in remarkably increased Escherichia-Shigella and Klebsiella becoming the predominant bacterial taxa. In contrast, the use of phage CKT1 significantly reduced Escherichia-Shigella and Klebsiella populations in intestine, permitting the proliferation of beneficial microbiota in Firmicutes including Lachnoclostridium, Ruminococcus, Lactobacillus, and Pseudoflavonifractor. In addition, phage alone treatments did not affect the normal gut microbiota structure of chicks, and phage therapy on Salmonella infected chicks increased bacteria species richness in the cecum. These results suggest that Salmonella phage CKT1 could improve growth performance of chicks challenged with S. Pullorum by normalizing the abnormal intestinal microbiome.

APAP-Induced IκBβ/NFκB Signaling Drives Hepatic Il6 Expression and Associated Sinusoidal Dilation.

Acetaminophen (APAP) overdose results in high morbidity and mortality, with limited treatment options. Increased understanding of the cellular signaling pathways activated in response to toxic APAP exposure is needed to provide insight into novel therapeutic strategies. Toxic APAP exposure induces hepatic nuclear factor kappa B (NFκB) activation. NFκB signaling has been identified to mediate the proinflammatory response but also induces a prosurvival and regenerative response. It is currently unknown whether potentiating NFkB activation would be injurious or advantageous after APAP overdose. The NFκB inhibitory protein beta (IκBβ) dictates the duration and degree of the NFκB response following exposure to oxidative injuries. Thus, we sought to determine whether IκBβ/NFκB signaling contributes to APAP-induced hepatic injury. At late time points (24 h) following toxic APAP exposures, mice expressing only IκBβ knock-in mice (AKBI mice) exhibited increased serologic evidence of hepatic injury. This corresponded with increased histologic injury, specifically related to sinusoidal dilatation. When compared with wild type mice, AKBI mice demonstrated sustained hepatic nuclear translocation of the NFκB subunits p65 and p50, and enhanced NFκB target gene expression. This included increased expression of interleukin-6 (Il-6), a known contributor to hepatic sinusoidal dilation. This transcriptional response corresponded with increased plasma protein content of Il-6, as well as increased activation of signal transducer and activator of transcription 3.

Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis caused by protozoan parasites of the genus Leishmania. Hepatomegaly is one of the most frequent clinical manifestations of VL, whereas immunopathology of the symptom has not been well investigated. Using our chronic model of experimental VL, we examined the influence of Leishmania donovani infection on the liver by clinical, histological, and biochemical analyses. The infected mice showed increased liver weight 24 weeks post-infection. Although an increase in serum ALT and inflammatory cell accumulation were observed in the livers of infected mice, no apparent parenchymal necrosis or fibrosis was observed. Tissue water content analyses demonstrated that increased liver weight was predominantly due to an increase in water weight. Together with the finding of hepatic sinusoidal dilation, these results suggested that edema associated with sinusoidal dilation causes hepatomegaly in L. donovani infection. Immunostaining of platelets and erythrocytes showed no thrombus formation or damage to the sinusoidal endothelium in the liver of infected mice. Taken together, these results suggest that hepatomegaly during experimental VL is caused by non-obstructive sinusoidal dilation.

English

This study evaluated if the oral administration of a bottled medicine containing Echinacea, Graviola, Purple Ipe, Sucupira and Cat’s claw could cause changes in biochemical, coagulation, hematological and histopathological parameters in rats. This study arised after a report to Ceatox of a patient who used a bottled medicine and developed hematological, renal and histopathological changes. The bottled medicine possesses 4.32 mg alcohol.mL-1 and by the phytochemical screening and UV/Scan tests showed some classes of secondary metabolites. In experiments using Wistar rats, two treatments were performed, single dose and 30 days, administering water, alcohol and bottled medicine by gavage. In the single dose treatment, alterations of uric acid, cholesterol, creatinine, alkaline phosphatase, iron and glucose (p<0.05) were found. Already in the 30 days treatment were alterations of uric acid, total and indirect bilirubins, creatinine, alkaline phosphatase, glucose, triglycerides, erythrocytes and leukocytes (p<0.05), and hepatic sinusoidal dilatation. The data showed that the alcohol present in the bottled medicine can alter biochemical, hematological parameters and cause liver damage in rats. The bottled medicine, although not showing alterations in important biochemical and hematological parameters, had more pronounced liver histopathological alterations. Key words: Bottled medicine, biochemical, coagulation and hematological parameters.

PSIX-16 Effects of dietary cadmium on production performance, hepatic injury and tissue residue in laying hens

Abstract Cadmium (Cd) is an environmental pollutant with destructive impact on many organ systems, such as chronic kidney diseases, liver diseases, osteoporosis, cardiovascular diseases and so on. The liver is the target organ of cadmium exposure. This study was performed to evaluate the adverse effects of prolonged high intake of dietary cadmium on production performance, serum biochemistry, liver antioxidant status, histopathology and the residue in liver and eggs in laying hens. 72 Hy-Line Brown laying hens aged 40 weeks were randomly allocated to four groups, with three replicates of six birds. Each group was fed a corn-soy basal diet (BD) and an oral dose of Cd at 0, 15, 30, 60 mg/kg per day for 6 weeks, respectively. Results revealed that the administration of 60 mg/kg Cd had no significant influences (P &amp;gt; 0.05) on production performance. Compared with the control, dietary Cd significantly increased (P &amp;lt; 0.05) the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, compared with the control, hepatic glutathione peroxide (GPX) activities were significantly decreased (P &amp;lt; 0.05), while malondialdehyde (MDA) was significantly increased (P &amp;lt; 0.05) when supplemented Cd over 15 mg/kg, and glutathione (GSH) was only decreased significantly (P &amp;lt; 0.05) in 30 mg/kg Cd group. Hepatic histopathology also showed hepatic injury, mild vasculitis and a small amount of lymphocyte infiltration occurred in the liver tissue in 15 mg/kg Cd group and the symptoms were exacerbated with the increased dose. In the 60 mg/kg group, hepatic sinusoidal dilatation and mild congestion were also observed. The residue of Cd in the liver and yolk were increased (P &amp;lt; 0.05) with the increasing concentration of dietary Cd. In conclusion, hepatic injuries in laying hens were induced when diets supplemented with Cd up to 15 mg/kg. Cd levels also managed to accumulated in liver and yolk of laying hens.

Toxicidad crónica del Cadmio y sus efectos sobre actividad de TGO, TGP, creatinina y alteración histológica en riñón e hígado en Rattus norvegicus variedad SPRAGUE DAWLEY

Se evaluó los efectos del cadmio sobre el peso corporal, la actividad de TGO, TGP, creatinina y los cambios histológicos en hígado y riñón de Rattus norvegicus variedad Sprague Dawley. La evaluación experimental se realizó en el Laboratorio de Fisiología Animal del Departamento Académico de Biología de la U.N.S.A.-Arequipa, durante los meses de Enero a Junio 2015. Se utilizaron 24 Rattus norvegicus variedad Sprague Dawley asignados en cuatro grupos:Control (Agua destilada), Grupo 2 (5 mg/Kg de cloruro de cadmio), Grupo 3 (10 mg/Kg. de cloruro de cadmio) y Grupo 4 (20 mg/Kg. de cloruro de cadmio) durante 4 semanas. Se encontró diferencia significativa (p&lt;0,05) en el peso corporal de las ratas en los diferentes grupos de evaluación. Al aplicar la prueba de postcomparación de Tukey se encontró que en el tratamiento con cloruro de cadmio en dosis de 20 mg/kg/día, los pesos corporales de las ratas intoxicadas disminuyeron significativamente. Se observó diferencia significativa (p&lt;0.01) en la actividad de TGO, TGP creatinina de las ratas en los diferentes grupos de evaluación. Al aplicar la prueba de postcomparación de Tukey, se encontró que en los tratamientos con cloruro de cadmio en dosis de 10 y 20 mg/kg/día los niveles de TGO, TGP y creatinina de las ratas intoxicadas se incrementaron significativamente. La exposición crónica de cloruro de cadmioprovocó congestión leve con dilatación de los sinusoides hepáticos y alteración del arreglo arquitectural de los hepatocitos; congestión vascular y aumento de la celularidad glomerular de moderado a severo, degeneración hialina del epitelio tubular en el riñón de las ratas que se les administró cloruro de cadmio en dosis de 10, 20 mg/kg/día durante 30 días.

Histologic, Metabolic, and Inflammatory Changes in the Liver of High-fat Diet-induced Obese Rats before and after Vitamin D Administration.

The current study aimed to investigate the effects of vitamin D administration on the markers of inflammation and metabolic damages in the liver of high-fat diet-induced obese rats. Forty male Wistar rats were divided into two groups of control receiving a normal diet (ND) and intervention receiving a high-fat diet (HFD). After 16 weeks, each group was divided into two groups including ND, ND + vitamin D, HFD, and HFD + vitamin D. Vitamin D was administered by oral gavage for five weeks at the dose of 500 IU/kg. Hepatic MCP-1, TGF-β, and NF-κB levels, serum liver enzymes, and serum lipids, and histological and structural changes in the liver were determined. Vitamin D administration significantly reduced the monocyte chemoattractant protein (MCP)-1 concentrations in the HFD + vitamin D group compared with the HFD group and reduced liver Transforming growth factor beta (TGF-β) levels in both vitamin D-treated groups (p<0.05). Moreover, a significant reduction in the serum levels of aspartate amino transferase (AST) and alanine amino transferase (ALT) in vitamin D treated groups was identified (p<0.05). A significant improvement in lipids and a pronounced improvement in the markers of liver histology damage including fat accumulation, aggregation of inflammatory cells, pre-apoptotic changes, hepatic sinusoidal dilatation, and necrotic pyknosis in the Kupffer cells were also identified. Our results demonstrated that vitamin D has potential effects in ameliorating the inflammatory, metabolic, and histologic changes in the liver of these animals.

Experimental infection by Anaplasma marginale in buffaloes and cattle: clinical, hematological, molecular and pathological aspects

ABSTRACT: The study aimed to evaluate and compare the clinical, laboratory and pathological aspects of buffalo and bovine experimentally infected with AmRio 2 strain of Anaplasma marginale. Four Murrah buffaloes and four crossbred cattle were used in the experiment, which two animals of each species were splenectomized. Strain AmRio 2 of A. marginale was inoculated in all experimental animals. Clinical exams, Packed Cell Volume (PCV), blood counts, blood smears, rickettsemia, necropsy and histopathology were performed in all cases. Semi-Nested-PCR (snPCR) for the msp5 and snPCR for the msp1α target gene for identification of A. marginale in blood samples from animals was done. From positive samples for msp1α snPCR, samples were analyzed for the amino acid sequences of this gene. Two splenectomized cattle presented apathy, pale mucous membranes, jaundice, hyperthermia, and severe anemia. The remaining experimental animals did not show clinical signs. The rickettsemia in all animals was less than 1%. The mean PCV of the splenectomized cattle was below 20% at two-time points after infection. On the blood count, the main changes were observed in splenectomized calves and were characterized by a decrease in red blood cells, hemoglobin, PCV and platelets (p &lt;0.05). All animals presented leukocyte elevation by increased lymphocytes, however, with no significant difference. The average prepatent period was two days in all the animals. The average incubation period in cattle that became ill was 25.5 days, and death occurred, on average, 63 days after inoculation of the strain. The necropsy findings were characterized by pale carcass, ascites, enlarged liver, distended gallbladder, and thick bile. Histopathological findings included infiltration of macrophages and lymphocytes in various organs, hepatic sinusoidal dilatation, and necrosis of the large intestine. In snPCR for the msp5 gene, 100% of the animals were positive in at least one evaluation. And in the snPCR for the infection of the msp1α target gene was also found in all animals in at least one sample evaluated. However, sequencing revealed only five animals, including the bovine which died, with a similarity of the amino acid sequences with AmRio 2 strain of A. marginale. It is concluded that the splenectomized cattle died due to anaplasmosis caused by the inoculated strain and the buffalo were more resistant compared to cattle. Buffaloes can be an alternative to cattle rearing in areas with a high occurrence of clinical cases of anaplasmosis.

The positive effect of metformin and metronidazole on the diabetic rats experimentally

Diabetes mellitus is considering most serious disease of endocrine, it affecting large number of people in worldwide. This study was performed to insured the effect of combination of metformin and metronidazole on disorder in metabolic that concomitant with injection of alloxan IP induced diabetes in rats. In this study forty male rats: divided into four groups including control group G1, alloxn group (150 mg/kg single dose) G2, alloxn group orally treated with metformin (150mg/kg/BW) G3, and alloxn group orally treated with metformin (150mg/kg/BW) and metronidazole (500mg/kg/BW) G4. The experiment last for 14 days. The result shows marked increase in MDA, glucose and also in liver enzymes, lipid profiles and even observed disorder in kidney function test by increased in the creatinine, urea, and uric acid levels. In addition to study the histological changes in diabetic liver of rats characterized by kupffer cells activation, dilation and congestion of central vein and hepatic sinusoids. Administration of metformin and combination of metformin and metronidazole, result in significant reduction return abnormal parameters to the normal values. Also correct the abnormal histological changes of liver.

Sub-Acute Oral Toxicity of a Novel Derivative of Agomelatine in Rats in a Sex-Dependent Manner.

Agomelatine (AGO) is a new type of antidepressant with demonstrated antidepressant effects and a unique modulating circadian rhythm action. However, AGO has hepatotoxicity, which limits its clinical application. In order to develop new drugs that cause less liver injury than AGO, a series of derivatives were synthesized; compound GW117 was screened from derivatives due to its high receptor affinity. This study will investigate its sub-acute oral toxicity profile in rats in a sex-dependent manner. GW117 and AGO was administrated by gavage (200, 400, or 800 mg/kg/day) for 28 days. Hematological, biochemical tests, organ weights, histopathological examinations were carried out, the results showed that AGO and GW117 had adverse effects on platelet, liver and kidney, and had sex-differences in some indicators. Hematological tests showed that AGO and GW117 reduced the platelet count in male animals but had no effect in females. AGO increased plasma alanine aminotransferase (ALT) and total bilirubin in male animals, and GW117 had no effect on these two indicators. For females, AGO moderately elevated ALT, alkaline phosphatase (ALP), and total bilirubin, while GW117 only elevated ALP slightly. Two drugs could increase liver weight and coefficient, and cause liver pathological injury, including hepatic sinusoidal dilatation, hepatocyte fatty deposition and dotted cell necrosis in two genders. AGO caused mild to moderate hepatocyte and hepatobiliary injury in both genders, while only a mild hepatobiliary injury was caused by GW117 in females. Renal function tests showed that both drugs can increase blood urea nitrogen levels in males, while AGO, but not GW117, can slightly increase blood creatinine and urea nitrogen in females. The kidney weight and coefficient could be significantly increased by two drugs in males, and by AGO medium and GW117 high and low doses in females. The kidney pathological damage was mainly characterized by tubule dilatation, a thinning of the renal cortex. Kidney damage caused by GW117 was less than that of AGO, and there was no sex-difference. In summary, GW117 can cause mild liver and kidney damage in both genders, as well as mild platelets reduction in males, while degree of damage is less severe than AGO. Therefore, as an excellent derivative, GW117 deserves further development as an antidepressant.