Changes In Hepatic Tissue Research Articles

Ameliorative effects of Turbinaria ornata extract on hepatocellular carcinoma induced by diethylnitrosamine in-vivo.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths and the fifth most common cancer worldwide. Brown algae appeared to be a rich source of efficient and safe agents against many life-threatening diseases like cancer. Thus, the scope of this study was to investigate the therapeutic effects of Turbinaria ornata against experimentally induced HCC in a rat model. Accordingly, forty male albino rats were divided into four groups. HCC was induced by intraperitoneal injection with diethylnitrosamine (DENA) followed by carbon tetrachloride (CCL4). After four weeks of DENA + CCL4 injection and two weeks of treatment with Turbinaria ornata, rats were sacrificed to collect hepatic tissue and blood samples for histopathological observations and various biochemical markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), urea, creatinine, albumin (ALB), and alkaline phosphatase (ALP). Rats that were injected for four weeks with DENA + CCL4 showed a significant increase in AFP levels, transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), as well as a high percentage of malignant changes in hepatic tissues. The extension of malignant changes in the rat liver tissues was markedly reduced using Turbinaria ornata, as the treatment displayed liver patterns similar to that of the normal control rats. Furthermore, rats with HCC fed with Turbinaria ornata extract for two weeks showed decreasing levels of TGF-β and TNF-α. These findings demonstrate that Turbinaria ornata supplement can prevent HCC development in hepatic rats; however, the exact mechanism requires further investigation.

Razvoj modela mašinskog učenja zasnovanog na algoritmu slučajnih šuma za detekciju promena u tkivu jetre nakon izlaganja česticama oksida gvožđa

Introduction/Aim: The aim of our study was to create a machine learning model, specifically a random forest model, which uses textural data from liver micrographs to differentiate between normal hepatic tissue and damaged tissue exposed to iron oxide nanoparticles. Material and Methods: Regions of interest in micrographs of hepatic tissue, obtained from mice treated with iron oxide nanoparticles and controls, were analyzed using the gray-level co-occurrence matrix (GLCM) method. The resulting GLCM features were employed as input data for the training and testing of the random forest model using the "Scikit-learn" library in the Python programming language. Additionally, a conventional decision tree model was developed, based on the classification and regression tree (CART) algorithm. Results: The random forest model outperformed the alternative CART decision tree approach in terms of classification accuracy, correctly predicting the class for 73.67% of the instances in the validation ROI dataset. The area under the receiver operating characteristic curve was 0.81, indicating relatively good discriminatory power. The F1 score for the model was 0.74, showcasing fairly good precision and recall, though not perfect. Conclusion: The data obtained from this study may be utilized for further development of artificial intelligence computation systems to identify physiological and pathophysiological changes in hepatic tissue. The results also serve as a starting point for additional research on the automation of histopathological analysis of liver tissue exposed to external toxic agents.

Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

Anti-inflammatory effects of oral and intraperitoneal administration of cerium oxide nanoparticles on experimental hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion (IR) injury occurs in liver surgery, resection, and transplantation. Reactive oxygen species (ROS) produced following IR starts the cascade of cell damage, necrosis/apoptosis, and proinflammatory responses by activating intracellular signaling cascade to drive hepatocellular damage. Cerium oxide nanoparticles (CONPs) act as anti-inflammatory and antioxidant agents. Thus, we evaluated the protective effects of oral (o.g.) and intraperitoneal (i.p.) administration of CONPs on hepatic IR injury. Mice were randomly divided into five groups: control, sham, IR protocol, CONP+IR (i.p.), and CONP+IR (o.g.). Mouse hepatic IR protocol was applied to the animals in the IR group. CONPs (300 μg/kg) were administered 24 hours before IR protocol. Blood and tissue samples were taken after the reperfusion period. Hepatic IR injury markedly increased enzyme activities, tissue lipid peroxidation, myeloperoxidase (MPO), xanthine oxidase (XO), nitrite oxide (NO), and tissue nuclear factor kappa-B (NF-κB) p65 levels, plasma pro-inflammatory cytokines, chemokines, and adhesion molecules while decreasing antioxidant markers and caused pathological changes in hepatic tissue. The expression of tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2), and 9 increased, and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) expression decreased in the IR group. Pretreatment with CONPs o.g. and i.p. 24 hours before hepatic ischemia improved the biochemical parameters above and alleviated the histopathological findings. Results of the present study demonstrate a significant reduction in liver degeneration by administering CONPs via i.p. and o.g. route in an experimental liver IR model, suggesting that CONPs have the extensive potential to prevent hepatic IR injury.

Ethambutol Effect on Renal and Hepatic Tissue Changes: A Literature Review

Background: Ethambutol is an oral chemotherapeutic drug specifically effective against the active growth of microorganisms of the genus Mycobacterium. Ethambutol is generally well-tolerated and rarely causes side effects. One of the commonly known side effects of ethambutol is optic neuritis, some others include peripheral neuropathy, numbness and tingling, hepatotoxicity, mental disorders, disorientation, hallucinations, to psychosis. Purpose: This review aims to explain current and previous opinions about ethambutol use and its effects on kidney and liver tissue. The results of this review are expected to provide an overview of the impact of using ethambutol caused tissue damage in humans. Methods: In this literature review, we performed a search for several keywords such as "ethambutol", "renal tissue", and "hepatic tissue” on PubMed, Science Direct, and Google Scholar databases from January 2010 to January 2022. Results: Combination antituberculosis therapy intervention of isoniazid, rifampin, pyrazinamide, and ethambutol causes elevated liver enzymes and drug-induced liver injury. Studies reported 14 of 634 (2%) patients on ethambutol are at risk for DILI. Antituberculosis medications have also been reported to affect the kidneys because of their association with the liver as part of the excretory system. Therefore, the kidneys are exposed to the harmful effects of intermediate or waste metabolism leading to injury in these cases. Conclusion: Ethambutol has not been shown to significantly cause damage to liver and kidney tissue, but it has been reported to have an impact on elevated liver enzymes and renal impairment supported by histological findings. Keywords: Ethambutol, renal tissue, hepatic tissue.

Improvement of the antioxidant activity of thyme essential oil against biosynthesized titanium dioxide nanoparticles-induced oxidative stress, DNA damage, and disturbances in gene expression in vivo

BackgroundTitanium dioxide nanoparticles (TiO2-NPs) are widely utilized in medicine and industry; however, their safety in biological organisms is still unclear. In this study, we determined the bioactive constitutes of thyme essential oil (TEO) and utilized the nanoemulsion technique to improve its protective efficiency against oxidative stress, genotoxicity, and DNA damage of biosynthesized titanium dioxide nanoparticles (TiO2-NPs). MethodsTEO nanoemulsion (TEON) was prepared using whey protein isolate (WPI). Sixty male Sprague-Dawley rats were divided into six groups and treated orally for 21 days including the control group, TEO, or TEON- treated groups (5 mg/kg b.w), TiO2-NPs-treated group (50 mg/kg b.w) and the groups received TiO2-NPs plus TEO or TEON. Blood and tissues samples were collected for different assays. ResultsThe GC-MS analysis identified 17 bioactive compounds in TEO and thymol and carvacrol were the major compounds. TEON was irregular with average particles size of 230 ± 3.7 nm and ζ-potential of −24.17 mV. However, TiO2-NPs showed a polygonal shape with an average size of 50 ± 2.4 nm and ζ-potential of −30.44 mV. Animals that received TiO2-NPs showed severe disturbances in liver and kidney indices, lipid profile, oxidant/antioxidant indices, inflammatory cytokines, gene expressions, increased DNA damage, and pathological changes in hepatic tissue. Both TEO and TEON showed potential protection against these hazards and TEON was more effective than TEO. ConclusionThe nanoemulsion of TEO enhances the oil bioactivity, improves its antioxidant characteristics, and protects against oxidative damage and genotoxicity of TiO2-NPs.

Quamoclit angulata extract supplementation attenuates hepatic damage via regulation of AMPK/SIRT associated hepatic lipid metabolism in streptozotocin and high fat diet–induced T2DM mice

Quamoclit angulata (QA) is a species of the Convolvulaceae family and has a regulatory effect on glucose homeostasis. However, the effects of QA on hyperglycemia-induced hepatic damage has not been elucidated. We hypothesized that QA extract (QAE) would alleviate hepatic damage through regulation of hepatic lipid accumulation in type 2 diabetes mellitus (T2DM). T2DM was induced by streptozotocin-high-fat diet in C57BL6 male mice for 8 weeks. The diabetic mice were supplemented with QAE at low dose (5 mg/kg) or high dose (HQ, 10 mg/kg) by oral gavage every day for 12 weeks. Histopathological changes in hepatic tissue were examined using hematoxylin and eosin staining, and the protein levels of biomarkers related to AMP-activation kinase (AMPK)/sirtuin-1 (SIRT1)-associated lipid metabolism were measured using Western blotting. QAE supplementation ameliorated plasma insulin and glycated hemoglobin in diabetic mice. Furthermore, QAE decreased hepatic lipid accumulation demonstrated by hepatic triglyceride and cholesterol levels. QAE supplementation induced hepatic AMPK, which activates SIRT1 accompanied by reduced lipogenesis in the HQ group. These changes were partially explained by the amelioration of advanced glycation end product, hepatic oxidative stress, inflammation, and fibrosis in diabetic mice. Altogether, QAE would be a potential nutraceutical to prevent hepatic damage by regulation of AMPK/SIRT1-associated lipid metabolism through oxidative stress, inflammation, and fibrosis in T2DM.

Mulberry fruit polysaccharides alleviate diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis in vivo: the roles of cell apoptosis and inflammation

ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and chemoprevention represents a feasible treatment to reduce the mortality of this carcinoma. Mulberry fruit polysaccharides (MFP) possess immunoregulatory and anti-inflammatory effects, which have been reported to alleviate liver damage evoked by CCl4 or alcohol in previous reports. However, its chemopreventive effect against liver carcinogenesis is insufficient. The present study was aimed to investigate the possible role of MFP as a pro-apoptosis, and anti-inflammatory agent to possess its chemoprevention property. Hepatocarcinogenesis was induced by diethylnitrosamine/phenobarbital (DEN/PB) for 14 weeks. The DEN/PB-administered rats were co-treated with different doses of MFP (50 or 100 mg/kg body weight) by oral gavage for 14 weeks. Basic hepatic function indexes (AST, ALT, ALP, GGT, total bilirubin, and albumin), and hepatic tumor biomarkers (AFP, CEA, and CA19.9), together with histological assessment were performed. Besides, the hepatic apoptosis markers (Bcl-2, Bax, caspase3, and caspase9), inflammation markers (IL-1β, TNF-α, and NF-κB), and mutT homologue gene 1 (MTH1) were examined. Oral gavage of MFP inhibited the elevations of hepatic function indexes and hepatic tumor biomarkers and alleviated pathological changes in hepatic tissue. In addition, the hepatic apoptosis markers, inflammation markers, and the mRNA level of MTH1 were abnormal in DEN/PB group, which were reversed by MFP treatment. In conclusion, MFP is an effective agent that provides chemoprevention against DEN/PB-evoked hepatocarcinogenesis via inhibition of inflammation and induction of apoptosis.

Therapeutic Effect of Biejiaxiaozheng Pills on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through the NF-κB/Nrf2 Pathway.

Aims To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-β, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-β, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. Results In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. Conclusion Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway.

Effect of a Fiber D-Limonene-Enriched Food Supplement on Intestinal Microbiota and Metabolic Parameters of Mice on a High-Fat Diet.

Several studies showed that D-Limonene can improve metabolic parameters of obese mice via various mechanisms, including intestinal microbiota modulation. Nevertheless, its effective doses often overcome the acceptable daily intake, rising concerns about toxicity. In this study we administered to C57BL/6 mice for 84 days a food supplement based on D-Limonene, adsorbed on dietary fibers (FLS), not able to reach the bloodstream, to counteract the metabolic effects of a high-fat diet (HFD). Results showed that daily administration of D-Limonene (30 and 60 mg/kg body weight) for 84 days decreased the weight gain of HFD mice. After 84 days we observed a statistically significant difference in weight gain in the group of mice receiving the higher dose of FLS compared to HFD mice (35.24 ± 4.56 g vs. 40.79 ± 3.28 g, p < 0.05). Moreover, FLS at both doses tested was capable of lowering triglyceridemia and also fasting glycemia at the higher dose. Some insights on the relevant fatty acid changes in hepatic tissues were obtained, highlighting the increased polyunsaturated fatty acid (PUFA) levels even at the lowest dose. FLS was also able to positively modulate the gut microbiota and prevent HFD-associated liver steatosis in a dose-dependent manner. These results demonstrate that FLS at these doses can be considered non-toxic and could be an effective tool to counteract diet-induced obesity and ameliorate metabolic profile in mice.

Di(2-ethylhexyl)phthalate exposure exacerbates metabolic disorders in diet-induced obese mice

Both phthalate exposure and obesity are positively associated with metabolic disorders. The study aimed to investigate whether DEHP exposure caused metabolic disorders in an obesity-dependent manner. Both lean and diet-induced obese mice were subjected to environmentally relevant DEHP exposure. DEHP-treated obese mice exhibited higher glucose intolerance and insulin resistance than obese mice; the metabolic disorders were accompanied by increased blood levels of leptin, LDL cholesterol, and alanine transaminase. In obese mice, DEHP enhanced macrophage infiltration into epididymal white adipose tissue (eWAT) and hepatic tissue, and promoted hepatic steatosis/steatohepatitis. The DEHP effects were not observed in lean mice. Transcriptomic changes in eWAT and hepatic tissue were determined with microarray analysis. Results indicated that obesity and DEHP synergistically regulated carbohydrate uptake, lipolysis, and abnormality of adipose tissue, via the upstream regulators Pparg, Lipe, Cd44, and Irs1. Meanwhile, obesity and DEHP differentially modulated transcriptomic changes in hepatic tissue. Obesity was associated with lipid/cholesterol synthesis, lipid accumulation, and inflammation in hepatic tissue via the upstream regulators Zbtb20 and Nr1i2. In obese mice, DEHP exposure caused hepatic injury, cell migration, and changes in glycogen quantity mainly via Cd44. Microarray analysis suggested the potential mechanism underlying the early onset of metabolic disorders in DEHP-treated obese mice.

Aspects of transition cow metabolomics—Part II: Histomorphologic changes in the liver parenchyma throughout the transition period, in cows with different liver metabotypes and effects of a metaphylactic butaphosphan and cyanocobalamin treatment

The aims of this study were to evaluate histopathologic changes during the transition period, describe the histopathological features of the metabotypes identified in Part I (Schären et al., 2021b), and investigate effects of a metaphylactic treatment with butaphosphan and cyanocobalamin (BCC) on the liver parenchyma. Eighty German Holstein cows (mean 305-d production: 10,957 kg, range: 6,480-15,193 kg; mean lactation number: 3.9, range: 2-9) from a commercial dairy farm in Saxony, Germany, were enrolled in a randomized, prospective, triple-blinded study. Two groups received a treatment with BCC (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin, Catosal, Bayer Animal Health, n = 20 each) and one group a placebo treatment (NaCl 0.9%, n = 40). Liver biopsy specimens were collected 14 d antepartum (AP) and 7, 28, and 42 d postpartum (PP), routinely processed for histologic examination, and stained with hematoxylin and eosin, Sudan III, periodic acid-Schiff, and picrosirius red stains. The sections were assessed for fat and glycogen content and degenerative, inflammatory, fibrotic, and proliferative changes. The statistical analysis included the effects of the sampling day, the lactation number, the treatment, and the metabotype (A = medium, B = minor, C = large alterations in the liver metabolome profile between AP and PP status). There was mild to moderate fat infiltration in the liver of 37% of cows in the last 2 wk AP, and moderate to severe fat infiltration in 66% of cows in the first days PP. The degree of fat infiltration increased from 2 wk AP until the end of the first week PP, and then decreased until the end of the study period, at which time about 25% of cows had moderate to severe fatty infiltration. Lipidosis was positively correlated with the severity of liver cell degeneration, and negatively correlated with the degree of glycogen deposits. Complete glycogen depletion of hepatocytes was not observed in cows, even in the presence of severe hepatic lipidosis. Moderate to severe lymphocytic hepatitis was seen in 39% of cows throughout the study period, and cows with lactation numbers 5 or greater had perisinusoidal fibrosis more often than younger cows. Severe fibrosis and cirrhosis of the liver did not occur. Metabotype B animals exhibited a higher chance of fatty infiltration, lower glycogen storage, and perisinusoidal fibrosis and for this metabotype positive correlations were calculated between increased fat deposition in the liver and marked glycogen depletion, and increased degenerative, inflammatory, fibrotic, and proliferative changes of hepatic tissue. For the treatment with BCC, no significant effect was observed. In summary, during the transition period, the liver of dairy cows is characterized by fat accumulation and glycogen depletion and histologic signs of hepatitis and hepatocyte degeneration. These histomorphologic changes were accentuated in animals exhibiting little alterations in their liver metabolome profile across the transition period (metabotype B) and support the assumption of a decreased grass silage quality as a causative factor.

Effect of Nigella sativa enriched diet on biochemical variables and antioxidant damage caused by silver nanoparticles toxicity in the African catfish, Clarias gariepinus

The present study aimed to investigate the effect of silver nanoparticles (AgNPs) (50 mg/L) on the behavioral changes, biochemical alterations, oxidative stress, and the histopathological changes in liver tissues of African catfish, clarias gariepinus. In addition to the potential role of Nigella sativa (NS) in ameliorating these effects. Fish were divided into four groups: group 1 was control fed on the basal diet, group 2 was fed on 3% (NS) of basal diet, group 3 was exposed to 50 mg/L AgNPs, and group 4 was exposed to 50 mg/L AgNPs and fed on 3% (NS) for 30 days. Results revealed that catfish in the group (3) exposed to AgNPs exhibited changes in skin pigmentation and abnormal behavior in the swim. A significant elevation (P<0.05) in levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of catfish exposed to AgNPs compared to the control fish. Furthermore, a marked increase in hepatic lipid peroxidation (LPO), catalase (CAT), total antioxidant (TAC), glutathione (GSH), and superoxide dismutase (SOD) levels were recorded in the group (3). Alternatively, feeding exposed catfish to AgNPs on 3% (NS) for 30 days, decreased the levels of ALP, AST, and ALT, improved the oxidative damage in liver tissues and attenuated the histological changes in hepatic tissues of C. gariepinus (group 4). Hence, this study suggested that (NS) has hepatoprotective and antioxidant effects in African catfish against AgNPs toxicity.

Paeoniflorin modulates oxidative stress, inflammation and hepatic stellate cells activation to alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1 in mice.

The role of Paeoniflorin on hepatic fibrosis and the specific mechanisms has not yet been elucidated. Therefore, we explored whether Paeoniflorin exerted protective effects on carbon tetrachloride (CCl4)-induced hepatic fibrosis and the underlying mechanisms. A model of hepatic fibrosis was induced by intraperitoneally injecting with CCl4 (10% 5 μl/g) twice a week for 7 weeks. To explore the effects of Paeoniflorin, mice were treated with Paeoniflorin (100 mg/kg) by gavage once a day at 1 week after modeling until they were sacrificed. Paeoniflorin remarkably improved liver function and histopathological changes of hepatic tissues in CCl4-induced liver injury. Besides, the serum MAO enzyme activity and hydroxyproline contents were notably decreased following the intervention of Paeoniflorin. The decreased expression of Vimentin, α-SMA, Col1a and Desmin manifested the inhibition of the hepatic stellate cells (HSCs) activation. Interestingly, Paeoniflorin intervention significantly upregulated the expression of heme oxygenase-1, and attenuated the inflammatory cytokines production as well as the CCl4-induced oxidative stress imbalance. Paeoniflorin could effectively alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1, and it might be a new effective option for the comprehensive treatment of hepatic fibrosis.

The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis

Fipronil (FIP) is a phenylpyrazole insecticide that is commonly used in agricultural and veterinary fields for controlling a wide range of insects, but it is a strong environmentally toxic substance. Exposure to FIP has been reported to increase the hepatic fat accumulation through altered lipid metabolism, which ultimately can contribute to nonalcoholic fatty liver disease (NAFLD) development. The present study aimed to examine the function of cerium oxide nanoparticles (CeNPs) in protecting against hepatotoxicity and lipogenesis induced by FIP. Twenty-eight male albino rats were classified into four groups: FIP (5 mg/kg/day per os), CTR, CeNPs (35 mg/kg/day p.o.), and FIP + CeNPs (5 (FIP) + 35 (CeNPs) mg/kg/day p.o.) for 28 consecutive days. Serum lipid profiles, hepatic antioxidant parameters and pathology, and mRNA expression of adipocytokines were assessed. The results revealed that FIP increased cholesterol, height-density lipoprotein, triacylglyceride, low-density lipoprotein (LDL-c), and very-low-density lipoprotein (VLDL-c) concentrations. It also increased nitric oxide (NO) and malondialdehyde (MDA) hepatic levels and reduced glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzyme activities. Additionally, FIP up-regulated the fatty acid-binding protein (FABP), acetyl Co-A carboxylase (ACC1), and peroxisome proliferator-activated receptor-alpha (PPAR-α). Immunohistochemically, a strong proliferation of cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba-1), cyclooxygenase-2 (COX-2) reactions in the endothelial cells of the hepatic sinusoids, and increased expression of caspase3 were observed following FIP intoxication. FIP also caused histological changes in hepatic tissue. The CeNPs counteracted the hepatotoxic effect of FIP exposure. So, this study recorded an ameliorative effect of CeNPs against FIP-induced hepatotoxicity.

Effects of free and nanoparticulate curcumin on chemically induced liver carcinoma in an animal model.

IntroductionCurcumin therapeutic applications are constrained by its prominent metabolic instability as well as inadequate absorption and bioavailability. The current study was designed to enhance the curcumin bioavailability by exploiting nanoparticles.Material and methodsEleven groups of mice were divided into: normal and nanoparticle control groups, a hepatocellular carcinoma (HCC) group induced by diethylnitrosamine (DEN), 2 groups treated with DEN plus a high dose/low dose of free curcumin, 2 groups treated with a high dose/low dose of free curcumin, 2 groups treated with DEN plus a high dose/low dose of nanoparticulate curcumin, and 2 groups treated with a high dose/low dose of nanoparticulate curcumin.ResultsDEN administration significantly increased liver enzymes, vascular endothelial growth factor, tumor necrosis factor-α, α-fetoprotein, malondialdehyde, and nucelar factor-κB. Also, it decreased serum albumin and tissue antioxidant activities and caused severe histological changes in hepatic tissue. Oral treatment of DEN-injected mice with either a high dose of free curcumin or the tested doses of nanoparticulate curcumin resulted in a significant improvement of all the tested parameters.ConclusionsAlthough the two tested doses of nanoparticulate curcumin were much lower than free curcumin, both doses were effective in preventing HCC development while the low dose of free curcumin was hardly effective. Hence, we conclude that nanoparticles enhance the bioavailability of curcumin.

Giardia duodenalis pathogenicity on immunosuppressed animal model.

Giardiasis is the major water-borne diarrheal disease present worldwide caused by the common intestinal parasite, Giardia duodenalis. This work aims to investigate the effect of G. duodenalis infection pathogenicity in immunosuppressed animals through histopathological examination. A total of 45 BALB/c mice were divided into four groups; G1 (negative control), G2 (healthy animals exposed to Giardia); G3 (immunosuppressed animals exposed to Giardia), and G4 (non-exposed immunosuppressed animals). Our study revealed that G3 was the most affected group with an infection rate of 100%. The animals showed general weakness, soft stool, and high death rate with severe histopathological changes in the duodenum and mild degenerative changes in hepatic tissues. In G2, the maximal lesions in both duodenum and liver were on the 11th day. We spotted damage in the villi, edema in the central core, and submucosa, in addition to increased cellular infiltration with inflammation in lamina propria. The presence of the parasites within the villi and the lumen was clear. Most of the hepatocytes revealed hydropic and fatty changes, also dilated congested central veins and edema were observed. G3 changes were more intense than G2 with massive Giardia trophozoites between the intestinal villi, lumen, and extensive fatty liver degeneration. Immune suppression plays a significant role in the severity of injury with the Giardia parasites in duodenum and liver cells.

Protective Role of Coenzyme Q10 in Acute Sepsis-Induced Liver Injury in BALB/c Mice.

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis.

Chlorella vulgaris ameliorates sodium nitrite-induced hepatotoxicity in rats.

The current was conducted to evaluate the ameliorating effect of Chlorella vulgaris (CV) extract against sodium nitrite-induced hepatotoxicity in rats. Forty-five rats were allocated randomly into 5 groups (n = 9). Group I (GI), control group: orally gavaged with normal saline daily. Group II (GII): orally gavaged with CV extract (70 mg/kg BW) for 3 months. Group III (GIII): orally gavaged with sodium nitrite (80 mg/kg BW) for 3 months. Group IV (GIV): received sodium nitrite as GIII and CV extract as GII simultaneously for 3 months. Group V (GV): received CV extract as GII and then, sodium nitrite as in GIII from the end of first month until the end of the experiment. Sodium nitrite significantly increased the activities of serum alanine aminotransferase, aspartate aminotransferase, and serum concentrations of tumor interleukin 1-β and necrosis factor α. In addition, it increased concentrations of malondialdehyde and nitric oxide and expression level of caspase-3 in the hepatic tissue. However, it decreased activities of hepatic glutathione peroxidase, catalase, and superoxide dismutase and induced degenerative and necrotic changes in hepatic tissues. In contrast, CV extract administration modulated sodium nitrite-induced inflammation, oxidative stress, and alteration in hepatic tissue function and architecture. This study indicated that CV extract modulated sodium nitrite-induced hepatic toxicity through decreasing oxidative stress and inflammation and enhancing antioxidant enzyme activities in hepatic tissue of rats.

Current Views of Torque Teno Virus (TTV) in Liver Diseases

Aim of review . We review published evidence on the torque teno virus (TT virus, TTV), which was discovered in the late of the 20th century. Key points . TTV is frequently confirmed in patients with hepatitises of viral origin or no definite viral aetiology, as well as in healthy people. Particular biochemical and histological changes in hepatic tissue and bile duct epithelium are reported for TTV monoinfection, which suggest viral replication in hepatocytes. At the same time, no cytopathic effects inherent in pathogenic hepatotropic viruses were revealed in hybridisation assays with TTV-infected cells. Novel data incited novel opinions on the TTV interaction with human. Earlier views of hepatotropic TTV gradually changed with newer evidence on its dispersion and coinfection with other viruses, including known hepatitis agents. Polytropism of TTV disproves its exclusive attribution to hepatitis viruses. High prevalence of the virus in human population argues in favour of its non-pathogenic persistence in the human viriome. TTV DNA content in blood is proposed as an endogenous immune status marker to observe prior to organ transplantation. Conclusion . High TTV dispersion in human population suggests its persistence in the human viriome. Seldom observed damaging effect of TTV on hepatic cells and bile duct epitheliocytes may indirectly suggest its opportunistic pathogenic properties.