Sinusoidal Congestion Research Articles

SITAGLIPTIN AMELIORATES ATORVASTATIN INDUCED HEPATOTOXICITY IN RATS

Atorvastatin (ATOR) is the most widely used statin for the treatment of hypercholesterolemia, which is the most common cause of severe liver injury. Sitagliptin is a selective dipeptidyl peptidase-4 inhibitor (DPP4-I) used clinically as oral anti-diabetic agent. This study aimed to identify the effect of sitagliptin (SITA) pretreatment against Atorvastatin (ATOR) induced hepatotoxicity in albino rats. Twenty-five rats were divided into five groups (5 rats in each); normal control, ATOR, SITA and two sitagliptin groups, which pretreated with sitagliptin 10 and 20 mg/kg/day in combination with ATOR 20mg /kg / day for eight consecutive days prior to ATOR. The results revealed that ATOR induced noticeable hepatic injury in the form of moderate Hepatoportal + sinusoidal congestion, all Zonal changes, moderate Cloudy swelling + hydropic degeneration, moderate Fatty change and mild Apoptosis. Biochemical analysis exposed a significant rise in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in ATOR group. Increased Proinflammatory TNF-alpha, Oxidative stress MDA and depressed antioxidant system of GSH were evident in ATOR group. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological changes induced by ATOR. In conclusion, sitagliptin ameliorated the hepatotoxicity induced by atorvastatin. This effect was probably based through suppression of inflammatory, oxidative stress and apoptotic processes. Sitagliptin might exert beneficial effect on diabetic hepatic disorders which mandate further clinical research.

Interventions in Budd-Chiari syndrome: an updated review.

Budd Chiari syndrome is a potentially treatable disease, and imaging is the key to its diagnosis. Clinical presentations may vary, ranging from asymptomatic to fulminant disease. Subacute BCS is the most common type encountered in clinical practice, characterized by ascites, hepatosplenomegaly, dilated abdominal wall veins, and varicosities in the lower limb and scrotum. While hepatic vein thrombosis is the leading cause in the West, membranous and short segmental occlusion are predominant in the Asian populations. These geographical variations have an impact on the treatment algorithm in managing BCS. Anticoagulation alone often fails to prevent disease progression, demanding further interventional therapy. Interventional therapy carries a lower morbidity and mortality than surgery. Anatomical recanalization and portosystemic shunting form the basis of endovascular management. Membranous or short-segment occlusion are best treated by angioplasty, which restores the physiological venous outflow and possibly disease reversal. Suboptimal results with angioplasty require stenting. Transjugular intrahepatic shunt (TIPS) or direct IVC to portal vein shunt (DIPS) decompresses the portal pressure and reduces the sinusoidal congestion, which in turn diminishes hepatocellular damage and hepatic fibrosis. Despite its ability to modify the disease course, TIPS carries several procedure and shunt-related complications, mainly hepatic encephalopathy. Thus, anatomical recanalization precedes TIPS in the traditional step-up approach in managing BCS. However, this concept is challenged by some authors, necessitating future reseach. TIPS is a valid bridge therapy in BCS with acute live failure awaiting liver transplantation. Despite all, interventional therapies fail in a subset of BCS patients, leaving them with only option of liver transplantation.

Exercise Preconditioning of the Donor Liver Decreases Cold Ischemia/Reperfusion Injury in a Mouse Model.

Liver transplantation stands as the primary treatment for end-stage liver disease, with demand surging in recent decades because of expanded indications. However, hepatic ischemia/reperfusion injury can lead to liver transplant failure in both deceased donor and living donor transplantation. This study explored whether preconditioning donor livers through exercise training (ExT) could mitigate cold ischemic injury posttransplantation. Donor C57BL/6 mice underwent ExT via treadmill running or remained sedentary. After 4 wk, the donor liver underwent cold storage and subsequent orthotopic liver transplantation or ex vivo warm reperfusion. Donor liver from mice subjected to ExT showed significantly decreased hepatic injury on reperfusion. Tissue histology revealed decreased sinusoidal congestion, vacuolization, and hepatocellular necrosis in livers from ExT mice, and immunofluorescence staining further revealed a decreased number of apoptotic cells in ExT grafts. Livers from ExT donors expressed decreased intragraft inflammatory cytokines cascade, decreased neutrophil infiltration and neutrophil extracellular traps, and increased M2 phenotype of recipient macrophages compared with grafts from sedentary mice. After cold storage, liver grafts from ExT donors showed decreased accumulation of reactive oxygen species and decreased levels of cytochrome c and high mobility group box 1 released in the liver effluent. In addition, ExT grafts showed upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and higher levels of mitochondrial content. Similar effects of decreased hepatic injury were observed in wild-type mice when pretreated with a PGC-1α stimulator ZLN005 instead of ExT. These findings suggest that augmenting hepatocytic mitochondrial content through donor exercise or PGC-1α stimulation may offer therapeutic avenues to mitigate postreperfusion inflammation and improve transplant outcomes.

Chronic aluminium chloride exposure induces redox imbalance, metabolic distress, DNA damage, and histopathologic alterations in Wistar rat liver.

Aluminium, a ubiquitous environmental toxicant, is distinguished for eliciting a broad range of physiological, biochemical, and behavioural alterations in laboratory animals and humans. The present work was conducted to study the functional and structural changes induced by aluminium in rat liver. Twenty five adult male Wistar rats (150-200 g) were randomly divided into five groups; control group and four Al-treated groups viz: Al 1 (25mg AlCl3/kg b.wt), Al 2 (35mg AlCl3/kg b.wt), Al 3 (45mg AlCl3/kg b.wt), and Al 4 (55mg AlCl3/kg b.wt). Rats in the aluminium-treated groups were administered AlCl3 for 30 days through oral gavage. Aluminium significantly increased the serum levels of liver function markers (ALT, AST, and ALP), phospholipids, and cholesterol. The activities of hepatocyte membrane (ALP, GGT, and LAP) and carbohydrate metabolic (G6P, F16BP, HK, LDH, MDH, ME, and G6PDH) enzymes were significantly altered by AlCl3 administration. Prolonged Al exposure induced oxidative stress in the liver, as evident by significant hepatocellular DNA damage, increased lipid peroxidation, and decreased non-enzymatic and enzymatic antioxidants. The toxic effects observed in this study were AlCl3 dose-dependent. Histopathological examination of liver sections revealed enlargement of sinusoidal spaces, derangement of the hepatic chord, loss of discrete hepatic cell boundaries, congestion of hepatic sinusoids, and degeneration of hepatocytes in Al-intoxicated rats. In conclusion, aluminium causes severe hepatotoxicity by inhibiting the hepatocyte membrane enzymes and disrupting the liver's energy metabolism and antioxidant defence.

Biochemical, Molecular, Postmortem and Histopathological Characterization of Bovine Theilerioses at Different Stages of Production and Reproduction

Theilerosis is the most important common vector (Tick) born and hemoprotozoan diseases (TBDS) which pose a serious threat to the livestock population in terms of mortality, reduced milk yield and lowered draft power. The disease is having impact on biochemistry and systemic functions affecting at different stages of production and reproduction of dairy cattle as well as there is lack of accurate diagnosis of this disease. A total 1900 cases were suspected for theileriosis on the basis of clinical signs and total 950 cases were found positive for theileriosis on the basis of blood smear examination. As per the stages of pregnancy and lactation, the cases were classified as cows in early pregnancy, cows in late pregnancy, cows in post parturient stage, cows in early and late lactation period. Biochemical alterations like increased AST, ALT and BUN level indicating liver and kidney dysfunctions in all the groups and significantly higher in post parturient group. The serum phosphorus, calcium and magnesium level decreased in all the affected groups and mostly in late pregnancy period and post parturient stage indicating metabolic disturbances during the disease which were aggravated during theileriosis. Through molecular diagnosis 114 cows (65.51%) were found positive for T. annulata and 41 cows (22.9%) were found positive for T. orientalis and 19 cows (10.9%) were found positive for both Theileria annulata and Theileria orientalis. Phylogenetic analysis revealed the accession number for Theileria annulata was OQ230445 which is having 100% similarity with puri isolate and 98% similarity with Khorda isolate and the accession number for T. orientalis was OQ 230446 having 85% similarity with Khorda isolate. On necropsy, the animals were weak, debilitated with atrophy of the muscles. In some cases, the liver was enlarged, markedly congested and in some cases yellowish tinged surface and cut edges with distension of gall bladder was evident. Abomasal ulcers were distinct and considered as pathognomonic. On histopathological examination, the liver revealed necrosis of hepatocytes with sinusoidal congestion and infiltration of mononuclear cells. In lymphnode, there was depletion of lymphocytes in lymphoid follicles with congestion and haemorrhage. Pulmonary edema was also evident in few cases. The combined approach involving biochemical, molecular, Post-mortem and histopathological characters were found to be fruitful in diagnosis of the bovine theileriosis at different stages of production and reproduction with optimum specificity.

Protective Effects of Stem Cells and Vitamin D3 Against Hepatic Ischemia/Reperfusion Injury in Rats

Abstract Background Liver transplantation is one of the most efficient life-saving treatments for various end-stage hepatic diseases. However, hepatic ischemic reperfusion injury (IRI) remains a major problem in liver surgeries morbidities and mortalities. Stem cells (SCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine, including liver diseases. Aim to investigate the effect of vitamin D and Bone Marrow Mesenchymal Stem Cells (BM- MSCs) solely or combined on hepatic IR injury. Methods Sixty adult male Wister rats were allocated into 5 groups; Sham, IR: underwent hepatic IR, vit. D-IR: received vit. D in a dose of 500 IU/Kg/day, by gavage, 5 days/week for 2 weeks, then subjected to hepatic IR, Stem cell-IR: received single IV injection of 1 × 106 BM-MSCs prior to hepatic IR and Combined-IR: received both vit. D and BM-MSCs prior to hepatic IR. All rats were subjected to estimation of Liver index (LI), assessment of serum levels of alanine, aspartate transaminases (ALT, AST) and vitamin D, hepatic tissue levels of Malondialdehyde (H.MDA), Superoxide dismutase (H.SOD), Interleukin-2, 10 (H.IL-2, H.IL-10), Caspase-3 (H.Casp-3), H.LC3B and hepatocyte growth factor (H.HGF), as well as histopathological liver examination and scoring. Results Hepatic IR resulted in significant elevation of ALT, AST and H.MDA, H.IL-2, H. Casp- 3 as well as significant reduction in LI, vit. D, H.SOD, H.IL-10, H.LC3B and H.HGF with evident hepatic sinusoidal congestion, cytoplasmic vacuolation and cellular necrosis. Treatment either solely or in combination mitigate these changes with the combined treatment showed the best results compared to the individual use. Conclusion In vivo coadministration of vitamin D and BM-MSCs prior to hepatic IR attenuated hepatocellular damage through preventing oxidative stress and inflammatory response, augmenting autophagic, regenerative capacity and anti-apoptotic effect.

Anti-inflammatory and anti-angiogenic effects of Withania somnifera extract on liver toxicity induced by silver nanoparticles in vivo.

The liver is a critical organ in the human body and is frequently exposed to numerous exogenous toxic substances, including silver nanoparticles (AgNPs). This study aimed to examine the anti-inflammatory, anti-angiogenic, and hepatoprotective effects of Withania somnifera (W. somnifera) extract on AgNP-induced liver toxicity in Swiss mice. Fifty mice were divided into five groups. Group I (negative control) consisted of ten mice. Group II received oral W. somnifera extracts (80 mg/kg/bw) for 14 days. Group III was injected intraperitoneally (i.p.) with AgNPs at a daily dose of 35 mg/kg/bw for 3 days. Group IV received i.p. AgNPs for 3 days, followed by saline for 14 days. Group V received i.p. AgNPs for 3 days, followed by oral W. somnifera (80 mg/kg/bw) for 14 days. Liver function tests, pro and anti-inflammatory cytokines, antioxidant activities, protein carbonyl (PC) levels, liver histopathological analysis, immunohistochemical expressions of transcription factor (NF-κB), and vascular endothelial growth factor (VEGF) were examined. Group III had elevated levels of liver function, a significant increase of pro and anti-inflammatory cytokines, antioxidant activity, and PC levels. Histological observations revealed congested sinusoids filled with red blood cells (RBCs) and hepatocyte necrosis. Also, positive expressions of NF-κB and VEGF were detected compared with Group I. However, the administration of W. somnifera to Group V revealed significant changes with evident improvements in liver function biomarkers, pro and anti-inflammatory cytokines, antioxidant activities, oxidative stress markers (PC), and histopathological and immunohistochemical parameters compared to Group III. The results revealed that W. somnifera has promising and potential hepatoprotective, anti-inflammatory, and anti-angiogenic effects against liver toxicity. Further detailed studies are recommended to explore the potential of W. somnifera as a treatment for human liver ailments.

Effects of Functional Pinealectomy on Immunity, Hematopoietic, Gastrointestinal and Urinary Systems in Experimentally Malnutritioned Rats

Objective: The aim of this study was to demonstrate morphological changes in immunity, hematopoietic, gastrointestinal and urinary systems in different melatonin (MEL) release situations in a rat model of protein energy malnutrition (PEM). Methods: A total of 32 adult male Wistar rats were assigned into four equal groups: normal control; PEM light/dark; PEM light, called functional pinealectomy (Px); and PEM dark. PEM was produced with a 50% restricted diet, Px was produced by keeping rats in continuous light environment for 24 hours, and complete blood count and serum albumin level were analyzed at the end of the 6-week experimental period. Measurements of weights of body and some visceral organs were obtained, biochemical and morphological parameters were analyzed in addition to measurements of malondialdehyde (MDA), total glutatione (GSH), tumor necrosis factor (TNF)-α and interleukin-10 (IL-10) in tissue samples. Results: A reduction in the weights of body and visceral organs of animals in the PEM groups was accompanied by hypoalbuminemia, anemia, leukopenia and lymphopenia, and higher MDA, GSH, TNF-α and IL-10 levels in visceral tissues. There was a significant decrease in parenchymal cells of the liver and spleen, duodenal villi, lymphoid structures and kidney glomeruli, but there was an increase in the spleen capsule thickness and renal Bowman’s space, sinusoidal congestion and fat accumulation in the liver. Importantly, these findings were milder in the PEM dark group, while they were prominent in the PEM light group. Conclusions: This study suggests that MEL has a protective role in reducing the negative effects of PEM, making it a potential therapeutic agent for further investigation.

The antihyperlipidemic effects of coenzyme Q10 and gemfibrozil on hyperlipidemic male rats: a comparative study

Dyslipidemia is considered as the most common risk factor for cardiovascular diseases, cerebrovascular diseases, and fatty liver disease. The available therapy aimed to decrease lipid profile and reduced long-term risk which do require lifelong therapy, hence adverse effects are suggestive. The goal of the present study is to compare the anti¬hyperlipidemic influence and hepatic side effects of CoQ10 and gemfibrozil in the hyperlipidemic male rats model. Twenty-five albino rats were divided into 5 groups: group 1(normal group), group 2 (olive oil group), group 3(hyperlipidemia-induced group) group 4 (CoQ10-treated group), and group 5 (gemfibrozil-treated group). Induction of hyperlipidemia lasts for 90 days and treatment lasts for 30 days. Serum liver enzyme analysis and liver histological study conducted to demonstrate the safety profile of the treatment agents. Analysis of the data revealed that the lipid profile parameters (except HDL) and liver enzymes were significantly (p< 0.001) higher in the hyperlipidemic group (Group 3) compared to either the control group (Group 1) or olive oil group. Using CoQ10 (Group 4) and gemfibrozil (Group 5) has revealed that the lipid parameters and liver enzymes were significantly (p<0.001) lower compared to the hyperlipidemic group (Group 3). Compared to control group, liver showed congestion of sinusoids, severe necrosis of hepatocytes, vacuolar degradation, and infiltration of inflammatory cells, these effects reversed in presence of CoQ10. Compared to gemfibrozil, CoQ10 provides safer and equally effective option for treatment of dyslipidemia represented by improved lipid parameters and liver enzymes alongside protected hepatic architecture.

Evaluation of the Spatial Arrangement of Rabbit Hepatocytes Based on Voronoi Tessellation Following Exposure to Zinc Oxide Nanoparticles.

Zinc oxide nanoparticles have been utilized in different fields over the last decades. These nanoparticles can pose significant risks to various organs such as the liver. This study aimed to evaluate the effects of zinc oxide nanoparticles on liver histology, serum biochemistry, and spatial arrangement of the hepatocytes in the female New Zealand white rabbit. The rabbits received 1, 5, and 10 mg/kg of the zinc oxide nanoparticles (ZnO NPs) intraperitoneally once every 3 days for 28 days. The serum levels of the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and zinc were assessed 48 hr following the first administration. The histopathological changes and Voronoi tessellation were evaluated after the last administration. Our findings showed that the ZnO NPs significantly increased the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and zinc. The histopathological findings showed ballooning degeneration, and sinusoidal congestion in ZnO NPs administrated groups. The Voronoi tessellation diagrams also confirmed that ZnO NPs changed the regular spatial arrangement of hepatocytes to random and cluster patterns. In conclusion, the ZnO NPs alter the liver spatial arrangement and induce hepatic pathological changes that may affect liver function in rabbits.

Histological Evaluation of the Protective Role of β-glucan Against Cisplatin-Induced Hepatotoxicity

Cisplatin is a commonly used chemotherapeutic agent in the treatment of many cancers. The most important dose-limiting side effect is hepatotoxicity. Some studies have shown that antioxidant treatment with cisplatin reduces the toxic effect. In the present study, we were aimed to investigate the protective effects of antioxidant β-glucan on histological injury caused by cisplatin treatment in the liver. Wistar rats were randomly divided into three groups according to time of sacrifice, 7th day and 14th day (n=20 rats each). Both groups were then divided into four sub-groups Control, Cisplatin (10 mg/kg bw), β-glucan (100 mg/kg bw) and cisplatin+β-glucan (n=5 in each group). The rats were sacrificed at the 7th day and 14th day after the last injection. The liver sections were evaluated under a light microscope after the histological procedure. Histological injury caused by cisplatin in different days were evaluated as as sinusoidal congestion, hydropic degeneration, disorganization of hepatic cords, and mononuclear cellular infiltration in liver. When β-glucan was administered with cisplatin, it was determined that cellular damage caused by cisplatin decreased considerably in the liver in the different days groups. The light microscopic examination showed that the antioxidant beta-glucan protects against hepatotoxicity caused by cisplatin with its free radical scavenging effect. In conclusion, β-glucan may improve patients' quality of life by reducing cisplatin's toxicity on the liver.

Histologic Findings of Sinusoidal Dilatation and Congestion in Liver Grafts Do Not Correlate with Hepatic Venous Anastomotic Gradients.

Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting. This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed. No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02). There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting.

Effect of Rutin on the Behavioural, Biochemical and Liver Morphological Changes in Danio Rerio Exposed to Reduced Graphene Oxide (Rgo) Nanoparticles

ABSTRACT: Reduced graphene oxide (rGO) is a carbon nanomaterial with unique characteristics that permit application in numerous fields. Rutin is a flavonoid with a variety of biological functions and pharmaceutical applications. In topical years, a handful of research has stated on the environmental impacts of carbon nanoparticles (NPs) and the consequences of reduced graphene oxide on the species that live in water bodies. However, the capacity to recuperate after exposure is still mostly unfamiliar. This study analyzed the protective effect of rutin against rGO NPs in zebrafish and the optimal dose required to inverse the impairment caused by rGO NPs exposure in zebrafish. In this study, fish were treated for 14 days and 8 study groups were examined: control, rGO exposure alone (10 mg/L), rutin exposure alone (50, 100 and 200 mg/L) and rGO combined with 3 distinct rutin doses (10 mg/L of rGO + rutin 50, 100, and 200 mg/L). In the zebrafish gill tissues, rGO impairs cells by increasing LPO levels and inducing oxidative stress by suppressing antioxidants (SOD, CAT, GPx, GSH, GR, GST, and vitamin C). Multiple alterations, including sinusoidal and venous congestion, vacuole formation or cytoplasmic vacuolation of hepatocytes, an enlarged hepatic plate gap, and necrosis, were revealed on the structural examination of liver tissues. Based on our results, we conclude that sub-lethal doses of rGO (10 mg/L) could be harmful to zebrafish. Rutin supplementation between 100 and 200 mg/L can protect against the toxic effects of rGO, even though rGO is detrimental to the exposed fish population.

Effect of the long-term use of a NOAEL dose of acetaminophen (paracetamol) on hepatic, renal, and neural tissues of aged albino rats.

Paracetamol is one of the most popular drugs; it is used daily by many people especially the elderly, without a limitation on the length of the period allowed for continuous use. Harms from long-term use are less clear, particularly in extrahepatic regions. This study aimed to investigate whether using paracetamol at a non-observable adverse effect level dose, known not to cause toxic effects, for a long period can induce toxicity in aged male albino rats. A daily dose of 500 mg per kg body weight of paracetamol was given to adult male albino rats for 12 weeks. During this period, rats were sacrificed at 4, 6, 8, 10, and 12 weeks to evaluate the toxic changes at several time intervals. Chemical analysis revealed elevated serum alanine transaminase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and declined level of total protein in N-acetyl-p-aminophenol (APAP)-treated group; it also caused oxidative stress, as shown by decreased glutathione, superoxide dismutase, and elevated malondialdehyde in the liver, kidney, and brain. Histopathological examination demonstrated cytoplasmic vacuolation and sinusoidal congestion with the development of single-cell necrosis in the liver. Renal tubular necrosis, glomerular atrophy, and ischemic neuronal injury, especially in the hippocampus were observed. the deleterious effects of APAP were increased in severity with increasing the period of treatment. Our results suggest that acetaminophen in a subtoxic dose for a long period could result in mild toxic effects on the liver but more serious lesions in the kidney and brain.

Liver histopathological and oxidative stress assessment by a combination of formaldehyde and oxytetracycline in sea bass (Dicentrarchuslabrax L).

Formaldehyde (FA) and oxytetracycline (OTC) are the chemicals commonly used in aquaculture to prevent or treat fish diseases due to protozoa, parasites, and bacteria. The goal of the present study is to assess the liver injury and oxidative stress induced by exposure of sea bass (Dicentrarchuslabrax L) to therapeutic doses of FA (200 ml.m-3) and OTC (40 g.m-3) under the same conditions being applied in intensive aquaculture systems in Tunisia. The liver histopathological survey was achieved after 5 and 10 days of exposure to FA, OTC separately or mixed. In parallel, liver catalase activity and malondialdehyde (MDA) were measured to assess oxidative stress. Results showed that treatment with FA and OTC used alone or in combinations induced liver damage as measured by sinusoid dilatation, intensive vacuolization, blood congestion, and focal necrosis. Significant elevation in catalyze activity and MDA levels were also observed in liver homogenates by the treatment (p ≤ 005). Combined treatment induced higher effects suggesting the critical hazards associated with FA and OTC when released to the environment.

Dilated cardiomyopathy in a green-winged saltator (Saltator similis)

Cardiovascular diseases are rarely reported in birds. Among pet birds, they are most documented in psittacine birds. Dilated cardiomyopathy is a myocardial disease frequently found in poultry but with few reports in both pet and wild birds. An elderly male green-winged saltator (Saltator similis) died suddenly after presenting intermittent clinical signs of dyspnea, weakness, and vocalization changes. A general increase in cardiac size with a bulging apex was observed at necropsy. The heart exhibited an enlarged left ventricular space and flaccid musculature on the cut section. The liver was diffusely enlarged with rounded edges. No other gross lesions were observed. Samples were collected in 10% formalin and routinely processed. Histologically, bundles of myocardial fibers were irregularly arranged, with markedly elongated myofibrils and irregular cell contours. Additionally, multifocal areas of disruption were observed between the myofibrils. Diffuse hepatic congestion of sinusoids and portal veins was observed, and diffuse edema in the interstitium and para bronchi was present in the lungs. The clinical signs observed were nonspecific and can be found in several diseases of the cardiovascular and respiratory systems of birds. The gross and histological findings are compatible with what has been described for dilated cardiomyopathy in birds; however, left ventricular dilatation is uncommon in avian patients. Heart diseases in pet birds are still underdiagnosed, and reports of cardiomyopathies are limited to psittacine birds. To the authors’ knowledge, this is the first report of a dilated cardiomyopathy in a passerine bird.

Histological evaluation of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: Correlation with Drum Tower Severity Scoring

BackgroundHepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids (PA-HSOS) is a complication of drug-induced liver damage. Few studies have examined the relationship between pathological changes and clinical circumstances in PA-HSOS. The Drum Tower Severity Scoring System (DTSS) was developed using prognostic indicators from clinical treatment outcomes. We hypothesized that the severity of pathological damage is consistent with DTSS. AimsWe aimed to improve our understanding and assessment of vascular liver injury disease histopathology by studying larger sample sizes of human histopathological samples. We also wanted to confirm the link between histopathological findings and DTSS. MethodsThe study included 62 patients with PA-HSOS who underwent transjugular liver biopsy. Their hepatic pathological tissues were evaluated. Analyses of linear regression and Spearman's correlation were employed to examine the relationship between DTSS and pathological characteristics. ResultsClinical performance and the DTSS score were used to determine histopathological severity. The sinusoidal congestion area (SCA), central venous endothelial injury (CVEI), and fibrinoid exudation in congestion foci (FECF) were significant indicators. SCA was linearly related to the DTSS score. ConclusionOur findings show that hepatic pathological characteristics correlate with DTSS scores in PA-HSOS. SCA, CVEI, and FECF may be helpful for determining PA-HSOS severity.

Precision Glycan Supplementation Improves Gut Microbiota Diversity, Performance, and Disease Outbreak Resistance in Broiler Chickens.

The poultry industry contributes significantly to the global meat industry but faces many production challenges like high-density housing, welfare issues, and pathogenic infections. While antibiotics have commonly been used to treat many of these issues, they are being removed from poultry production globally due to increased microbial resistance. Precision glycans offer a viable alternative to antibiotics by modulating microbial metabolic pathways. In this study, we investigated the effects of precision glycan supplementation on productivity and gut microbiota in broilers. The experiment was conducted in a commercial setting using 32,400 male Ross chickens randomly divided into three sheds with 10,800 birds each. One shed with 12 pen replicates of 900 birds was used as control, while the other two with an equal number of replicates and birds were assigned to precision glycan supplementation. The treatment significantly improved the average daily weight gain and feed conversion ratio, with a significant modification in the abundance of several bacterial taxa in the caecum, ileum, and ileum mucosa microbial communities. There was increased richness and diversity in the caecum, with a reduction in Proteobacteria and an increase in Firmicutes. Richness remained unchanged in the ileum, with an increase in diversity and reduction in pathogenic genera like Clostridium and Escherichia-Shigella. Ileum mucosa showed a lower abundance of mucin degraders and an increased presence of next-generation probiotics. Supplemented birds showed a high level of disease resistance when the farm experienced an outbreak of infectious bronchitis, evidenced by lower mortality. Histological analysis confirmed improvements in the ileum and liver health, where the precision glycan supplementation reduced the area of congested sinusoids compared to the control group in the liver and significantly improved ileum intestinal morphology by increasing crypt depth and surface area. These results collectively suggest that precision glycans offer substantial benefits in poultry production by improving productivity, gut health, and disease resistance.

A study of the anti-fibrotic effect of ghrelin on mice with nonalcoholic steatohepatitis

Objective: To study the anti-fibrotic effect of ghrelin on high-fat diet-induced non-alcoholic steatohepatitis (NASH) in mice. Methods: 24 male C57BL/6 mice were randomly divided into a normal diet group, a normal diet + ghrelin group, a high-fat diet group, and the high-fat diet + ghrelin group. The HFD and HFD+ghrelin groups were fed high-fat diet for 16 weeks to induce non-alcoholic steatohepatitis. Among them, the NCD+ghrelin group and HFD+ghrelin group were continuously given ghrelin intervention (11nmol·kg(-1)·d(-1)) for 2 weeks after feeding for 14 weeks. 16 mice were euthanized on weekends. The plasma levels of alanine aminotransferase (ALT) and hyaluronic acid (HA) were measured in mice. The content of hydroxyproline (Hyp) was determined in liver tissue. RT-qPCR was used to detect the mRNA expression levels of transforming growth factor β1 (TGF-β1) and collagen types I, III, and IV in liver tissue. A Western blot was used to detect the expression level of the α-smooth muscle actin (α-SMA) protein in liver tissue. HE staining was used to observe the morphological changes in liver tissue. VG staining was used to observe the fibrotic condition in liver tissue. Results: Compared with the NCD group, plasma ALT (266.80±146.80)U/L, HA (219.00±39.47) ng/ml levels, Hyp content (0.35±0.05)μg/mg prot (P < 0.05), mRNA expression levels of transforming growth factor β1 (TGF-β1) and collagen types I, III, IV (P < 0.05), and the expression level of α-SMA protein in the HFD group were significantly increased (P < 0.05), with congestion in the hepatic central lobular veins, hepatocytes swelling, and deposition of a large amount of collagen fibers in liver tissue. Compared with the HFD group, plasma ALT (57.17±20.88)U/L, HA (75.68±8.40)μg/mg levels, Hyp content (0.19±0.07)μg/mg prot, mRNA expression levels of transforming growth factor β1 (TGF-β1) and collagen types I, III, IV (P < 0.05), and the expression level of α-SMA protein in the HFD+ghrelin mice group was significantly reduced (P < 0.05), with only mild sinusoidal congestion in the liver tissue but significant improvement and reduction in liver injury and collagen fiber deposition. Conclusion: Ghrelin has a significant improvement effect on liver fibrosis in NASH mice.

PROTECTIVE EFFECTS OF GRAPE SEED EXTRACT (VITIS VINIFERA) AGAINST CISPLATIN-INDUCED LIVER DAMAGE IN RABBITS. (HISTOLOGICAL AND HISTOPATHOLOGICAL STUDY)

Cisplatin is a chemotherapeutic drug used in the treatment of various cancer types. It can be considered a double-edged sword. It is a potent anticancer agent at the same time has toxic effect on various tissues as it causes hepatotoxicity. It was determined to cause liver toxicity and to weaken the antioxidant defense systems in liver. A decrease in antioxidant enzymes resulted from cisplatin induced tissue toxicity. Moreover, the development of therapies to prevent the appearance of cisplatin- induced tissue toxicities has focused on administration of antioxidants along with cisplatin treatment. The grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Therefore, the aim of present study was designed to investigate the protective effects of grape seed extract on the liver damage in cisplatin treated rabbits. Twenty seven healthy rabbits of local mixed breed were selected, divided into three equal groups, the first group (CON group) served as control and received a single intraperitoneal injection of normal saline solution once per week for 6 weeks; the second group (CIS group) were treated with therapeutic dose of cisplatin intraperitoneally once per week for six weeks; the third group (CIS+GSE group) served as protective group and was concomitantly treated with grape seeds extract by oral gavages and cisplatin injection intraperitoneally once per week for six successive weeks. Administration of grape seeds extract by oral gavages starting from the first day of the experiment for 6 consecutive days before and 6 consecutive days after the cisplatin injection and continued daily for 6 weeks. The histopathological findings present in current study showed that cisplatin toxicity produced significant structural changes in the liver of CIS group, cisplatin treated group, in the form of prominent disorganized architecture and loss of liver lobulation, distortion of the arrangement of parenchyma of the liver, loss of radial arrangement of sinusoids from the central vein of the liver, Dilatation and congestion of central veins, sinusoids and portal traids, degenerative changes in hepatocytes and pyknotic nuclei indicating necrosis. Marked vacuolar degeneration mainly hydropic ballooning degeneration and hyper activation of Kupffer cells and inflammatory cellular infiltrations were also observed. This finding reflected the cytotoxic effects of cisplatin in hepatic tissue. While, in the sections from the liver of animals received therapeutic dose of cisplatin and treated by grape seed extract, group (CIS+GSE) clearly showed that there was a significant alleviated hepatotoxicity, since histopathological changes were markedly less pronounced compared to animals treated with cisplatin alone. Therefore, and based on our findings, the grape seed extract contributes significantly to the improvement of histological alterations in rabbit liver caused by cisplatin.