Liver Sections Research Articles

DESI-MSI-based technique to unravel spatial distribution of COMT inhibitor Tolcapone

Ascertaining compound exposure and its spatial distribution are essential steps in the drug development process. Desorption electrospray ionization mass spectrometry (DESI-MSI) is a label-free imaging technique capable of simultaneously identify and visualize the distribution of a diverse range of biomolecules.In this study, DESI-MSI was employed to investigate spatial distribution of tolcapone in rat liver and brain coronal – frontal and striatal –sections after a single oral administration of 100 mg/Kg of tolcapone, brain-penetrant compound.Tolcapone was evenly distributed in liver tissue sections whereas in the brain it showed differential distribution across brain regions analyzed, being mainly located in the olfactory bulb, basal forebrain region, striatum, and pre-frontal cortex (PFC; cingulate, prelimbic and infralimbic area). Tolcapone concentration in tissues was compared using DESI-MSI and liquid-chromatography mass spectrometry (LC-MS/MS). DESI-MSI technique showed a higher specificity on detecting tolcapone in liver sections while in the brain samples DESI-MSI did not allow a feasible quantification. Indeed, DESI-MSI is a qualitative technique that allows to observe heterogeneity on distribution but more challenging regarding accurate measurements.Overall, tolcapone was successfully localized in liver and brain tissue sections using DESI-MSI, highlighting the added value that this technique could provide in assisting tissue-specific drug distribution studies.

Feeding of Hermetia illucens Larvae Meal Attenuates Hepatic Lipid Synthesis and Fatty Liver Development in Obese Zucker Rats.

The present study tested the hypothesis that dietary insect meal from Hermetia illucens (HI) larvae attenuates the development of liver steatosis and hyperlipidemia in the obese Zucker rat. To test the hypothesis, a 4-week trial with male, obese Zucker rats (n = 30) and male, lean Zucker rats (n = 10) was performed. The obese rats were assigned to three obese groups (group O-C, group O-HI25, group O-HI50) of 10 rats each. The lean rats served as a lean control group (L-C). Group L-C and group O-C were fed a control diet with 20% casein as protein source, whereas 25% and 50% of the protein from casein was replaced with protein from HI larvae meal in the diets of group O-HI25 and O-HI50, respectively. The staining of liver sections with Oil red O revealed an excessive lipid accumulation in the liver of group O-C compared to group L-C, whereas liver lipid accumulation in group O-HI25 and O-HI50 was markedly reduced compared to group O-C. Hepatic concentrations of triglycerides, cholesterol, C14:0, C16:0, C16:1, C18:0, C18:1, the sum of total fatty acids and hepatic mRNA levels of several genes associated with lipid synthesis and plasma concentration of cholesterol were markedly higher in group O-C than in group L-C, but lower in group O-HI50 than in group O-C (p < 0.05). In conclusion, partial replacement of casein by HI larvae meal attenuates liver steatosis and dyslipidemia in obese Zucker rats. This suggests that HI larvae meal serves as a functional food protecting from obesity-induced metabolic disorders.

A novel pathologic marker, indoleamine 2,3-dioxygenase 1, for the cholangiopathy of immune checkpoint inhibitors-induced immune mediated hepatotoxicity as adverse events and the prediction of additional ursodeoxycholic acid treatment.

Immune-related adverse events (irAE) has been clarified according the usage of immune checkpoint inhibitors(ICI). We primarily found indoleamine 2,3-dioxygenase 1(IDO-1) as a histologic biomarker for the cholangiopathy of primary biliary cholangitis(PBC). In this study, we evaluated the utility of IDO-1 in identifying ICI-induced immune-mediated hepatotoxicity(IMH). Immunostaining for IDO-1 using liver sections of PBC, ICI-induced IMH and controls, revealed that IDO-1 expression in bile ducts is mostly restricted in PBC and ICI-induced IMH. In ICI-induced IMH, IDO-1-positive bile ducts is found in 2/2 cases of cholangitis type and also positive/focal ducts in 11/15 cases of hepatitis type. Moreover, in 8/13 positive/focal cases, ursodeoxycholic acid as well as steroids were needed to improve liver dysfunction, but just one case (1/4) in IDO-1-negative cases. One IDO-1 positive case of hepatitis type did not receive additional UDCA, but biliary enzymes worsen. In vitro study using cultured human biliary epithelial cells revealed that IDO-1 induction was found with the stimulation of IFN-γ. In conclusion, the presence of IDO-1-positive cells is found in bile ducts in hepatitic type as well as sclerosing cholangitis of ICI-induced IMH. IDO-1 is surely a valuable pathologic marker for diagnosing ICI-induced IMH and also for predicting an additional need of UDCA in clinical practice.

Cyclosporine Ameliorates Silica-Induced Autoimmune Hepatitis in Rat Model by Altering the Expression of Toll-Like Receptor-4, Interleukin-2, and Tumor Necrosis Factor-α.

Autoimmune hepatitis (AIH) is an inflammatory liver disease that is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor α (TNF-α) are potent inflammatory cytokines secreted in AIH, playing an important role in the early development of inflammation and hepatocyte damage. This study examined the role of cyclosporine in AIH and illustrated its actions on altered hepatic function in the silica-induced AIH model. AIH was induced in Wistar rats using sodium silicate. The rats were divided into four groups: the control group, silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4 and IL-2 mRNA expressions in liver tissues were tested by RTPCR. AIH was associated with up-regulation of liver enzymes, IL-2 and TLR-4 gene expression, while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1±0, 13.57±1.91, 4±0.38, and 2±0 in control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Also, the relative quantity of IL-2 mRNA was 1±0, 14.79±1.42, 7.07±0.96, and 3.4±0.55 in control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Additionally, immunohistochemical staining for TNF-α in liver sections was increased in the silica-AIH group but was found to decrease in the cyclosporine-treated and prevention groups. This study advocates the therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.

Biochanin A in murine Schistosoma mansoni infection: effects on inflammation, oxidative stress and fibrosis.

Biochanin A (BCA) is a multifunctional natural compound that possesses anti-infective, anti-inflammatory, anti-oxidative and hepatoprotective effects. The aim of the study was to assess the therapeutic efficacy of BCA on Schistosoma mansoni-infected mice. Fifty mice were divided into six different groups as non-infected, non-infected BCA-treated, infected untreated, early infected BCA-treated (seven days post-infection (dpi)), late infected BCA-treated 60 dpi and infected praziquantel (PZQ)-treated groups. Parasitological, histopathological examination and immunohistochemical staining of transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) were investigated in liver sections. Cytochrome P450 (CYP450) gene expression of S. mansoni was evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). A single dose of BCA significantly reduced worm burden in early (82.14%) and late infection (77.74%), mean tissue egg load in early (7.27 ± 0.495) and late BCA administration (7.63 ± 0.435) and decreased granuloma size. CYP450 mRNA expression was significantly reduced in early BCA treatment as compared to late treatment which emphasizes that early administration of BCA had more pronounced effects on worms than late administration. Both early and late BCA administration led to significant reduction in inflammatory cytokines as TGF and iNOS. Although the reduction of TGF and iNOS in BCA-treated mice was superior to PZQ, no statistically significant differences were noted. However, a significant downregulation of COX2 was noted in hepatocytes as compared to both infected control and PZQ-treated mice. BCA has schistosomicidal, anti-inflammatory, antioxidant and anti-fibrotic effects and could be regarded as a potential drug in schistosomiasis treatment.

Single-cell and spatiotemporal transcriptomic analyses reveal the effects of microorganisms on immunity and metabolism in the mouse liver

The gut-liver axis is a complex bidirectional communication pathway between the intestine and the liver in which microorganisms and their metabolites flow from the intestine through the portal vein to the liver and influence liver function. In a sterile environment, the phenotype or function of the liver is altered, but few studies have investigated the specific cellular and molecular effects of microorganisms on the liver. To this end, we constructed single-cell and spatial transcriptomic (ST) profiles of germ-free (GF) and specific-pathogen-free (SPF) mouse livers. Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) revealed that the ratio of most immune cells was altered in the liver of GF mice; in particular, natural killer T (NKT) cells, IgA plasma cells (IgAs) and Kupffer cells (KCs) were significantly reduced in GF mice. Spatial enhanced resolution omics sequencing (Stereo-seq) confirmed that microorganisms mediated the accumulation of Kupffer cells in the periportal zone. Unexpectedly, IgA plasma cells were more numerous and concentrated in the periportal vein in liver sections from SPF mice but less numerous and scattered in GF mice. ST technology also enables the precise zonation of liver lobules into eight layers and three patterns based on the gene expression level in each layer, allowing us to further investigate the effects of microbes on gene zonation patterns and functions. Furthermore, untargeted metabolism experiments of the liver revealed that the propionic acid levels were significantly lower in GF mice, and this reduction may be related to the control of genes involved in bile acid and fatty acid metabolism. In conclusion, the combination of sc/snRNA-seq, Stereo-seq, and untargeted metabolomics revealed immune system defects as well as altered bile acid and lipid metabolic processes at the single-cell and spatial levels in the livers of GF mice. This study will be of great value for understanding host-microbiota interactions.

Assessment of haematological and histopathological effects of mixture toxicity of phenanthrene and benzo[a]pyrene in catfish

The effect of joint mixtures of phenanthrene and benzo[a]pyrene on selected haematological and histopathological parameters of the Clarias gariepinus was investigated. Healthy juvenile C. gariepinus (n = 90) weighing 19.7 ± 1.8 g were exposed to sublethal concentrations of joint mixtures of phenanthrene and benzo[a]pyrene for a subchronic period of 35 days. Acute toxicity studies showed that phenanthrene and benzo[a]pyrene had LC50 values of 1400 and 16 μg/L respectively while the safe limits of the chemicals varied in the ranges of 0.00016 to 1.6 μg/L and 0.014 to 140 μg/L for benzo[a]pyrene and phenanthrene respectively. The joint mixture significantly (p &lt; 0.05) reduced growth rate in exposed fish. The joint mixtures also led to significant (p &lt; 0.05) declines in the studied haematological parameters including blood cell count (RBC), haemoglobin (Hb) and haematocrit (Hct). The erythrocyte indices including mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) all showed significant (p &lt; 0.05) declines in the presence of the joint toxicants. There were significant (p &lt; 0.05) increases in white blood cells (WBC) count and platelet (PLT) count. Histopathological examination showed alterations in liver and gill sections of exposed fish

Investigating the Diagnostic Utility of Cola acuminata Extract as an Alternative Histological Cytoplasmic Stain

Background: Stains are essential artefacts which aid visualisation and evaluation of histological specimens. However, the use of synthetic dyes for diagnostic purpose has become a major concern a threat to sustainable development owing to the associated toxicity, environmental pollution and potential risk to human health. Several studies have investigated the application of naturally occurring pigments in plants use of natural dyes for clinical and diagnostics purposed. The study investigated the application of naturally occurring pigments of Cola acuminata extract for clinical and diagnostics purpose; specifically, as a histological cytoplasmic stain. Methods: Formalin-fixed, paraffin-embedded tissue sections from cattle heart, liver and spleen were stained by varying concentrations of Cola acuminata nuts extracts, with different extractants including absolute methanol, ethanol and distilled water at different times. Tissue sections stained with dye extracts produced a spectrum of greyish to golden brown cytoplasmic colouration. Results: Cola acuminata dye extracts produced relatively varying staining intensities of golden-brownish cytoplasmic colouration applied on liver, spleen and heart tissue sections cattle tissue with different extractants, at different concentrations and staining times, comparable to eosin, and with blue purple heamatoxylin nuclear stain. Methanolic dye extract (60% w/v) of Cola acuminata at an acidic pH, applied for 15min at room temperature, yielded the best staining result. Conclusion: Cola acuminata nut dye extract is a potential substitute for cytoplasmic synthetic dye utility in histological staining techniques. Further research needed to reinforce and validate its applicability in a wide range of pathological specimens.

Enhancing the accuracy of mid-infrared spectroscopy-based liver steatosis quantification using digital image analysis as a reference.

The assessment of liver steatosis is crucial in both hepatology and liver transplantation (LT) surgery. Steatosis can negatively impact the success of LT. Steatosis is a factor for excluding donated organs for LT, but the increasing demand for transplantable organs has led to the use of organs from marginal donors. The current standard for evaluating steatosis is a semi-quantitative grading based on the visual examination of a hematoxylin and eosin (H&E)-stained liver biopsy, but this method is time-consuming, subjective, and lacks reproducibility. Recent research has shown that infrared (IR) spectroscopy could be used as a real-time quantitative tool to assess steatosis during abdominal surgery. However, the development of IR-based methods has been hindered by the lack of appropriate quantitative reference values. In this study, we developed and validated digital image analysis methods for the quantitation of steatosis in H&E-stained liver sections using univariate and multivariate strategies including linear discriminant analysis (LDA), quadratic DA, logistic regression, partial least squares-DA (PLS-DA), and support vector machines. The analysis of 37 tissue samples with varying grades of steatosis demonstrates that digital image analysis provides accurate and reproducible reference values that improve the performance of IR spectroscopic models for steatosis quantification. A PLS model in the 1810-1052 cm-1 region using first derivative ATR-FTIR spectra provided RMSECV = 0.99%. The gained improvement in accuracy critically enhances the applicability of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) to support an objective graft evaluation at the operation room, which might be especially relevant in cases of marginal liver donors to avoid unnecessary graft explantation.

Effects of Ethanolic Extracts of Fruits of Dennettia tripetala on Liver Function of Male Albino Rats

This study evaluated the effects of ethanolic extracts of fruits of Dennettia tripetala on liver function of male albino rats. Dennettia tripetala is an endemic plant of west tropical Africa that is known as pepper fruit. The fruit is known for its numerous medicinal properties such as antioxidant, anti-inflammatory and antidiarrhea. The plant materials were air dried and made into powder, 250g was used for the crude extraction using 70% ethanol. Ninety eight male albino rats were used in this study; forty eight were used for LD50 and fifty for the main experiment. The animals were randomly distributed into 5 groups of 10 animals each. The test animals were administered single dose of ethanolic extracts of fruits of D. tripetala (200 mg/kg and 400 mg/kg) daily for twenty-one days. The animals sacrificed at end of the 21 days. Blood sample was collected via cardiac puncture for biochemical analysis, while the liver was harvested for histological examination. A very high LD50 value of 4000 mg/kg body weight was recorded in this study. The results of biochemical parameters revealed that mean values of AST ALT and ALP were elevated significantly (p&lt;0.05) in all the test groups, except ALP in group 4 which showed no significant alteration when compared to the control. Total protein, albumin and globulin showed no significant alteration in all the test groups; total and direct bilirubin decreased significantly in test groups 4 and 5, and increased in group 2, while indirect bilirubin showed no significant alteration in all the test groups. Photomicrograph of liver section of normal control rats (group 1) showed normal central vein, portal triad, sinusoids and lamella of hepatic cells as well as those in all the test groups.

Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death.

Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (HFPO-DA) is a short chain member of per- and polyfluoroalkyl substances (PFAS). To better understand the relevance of histopathological effects seen in livers of mice exposed to HFPO-DA for human health risk assessment, histopathological effects were summarized from hematoxylin and eosin (H&E)-stained sections in several repeat-dose toxicity studies in mice. Findings across studies revealed histopathological changes consistent with peroxisomal proliferation, whereas two reports of steatosis could not be confirmed in the published figures. In addition, mechanisms of hepatocellular death were assessed in H&E sections as well as with the apoptotic marker cleaved caspase-3 (CCasp3) in newly cut sections from archived liver blocks from select studies. A comparison of serially CCasp3 immunolabeled and H&E-stained sections revealed that mechanisms of hepatocellular death cannot be clearly discerned in H&E-stained liver sections alone as several examples of putatively necrotic cells were positive for CCasp3. Published whole genome transcriptomic data were also reevaluated for enrichment of various forms of hepatocellular death in response to HFPO-DA, which revealed enrichment of apoptosis and autophagy, but not ferroptosis, pyroptosis, or necroptosis. These morphological and molecular findings are consistent with transcriptomic evidence for peroxisome proliferator-activated receptor alpha (PPARα) signaling in HFPO-DA exposed mice.

Sub-acute toxicity of graphene oxide (GO) nanoparticles in male mice after intraperitoneal injection: Behavioral study and histopathological evaluation.

Graphene oxide (GO) is a graphene derivative used for numerous applications in which biomedical uses are significant. However, for this application, the security of GO is doubtful. In this work, we synthesized this nanoparticle to assess its toxicity in male mice. In addition, we studied the effects of this nanomaterial on behavior by administering GO intraperitoneally to mice at different doses (2mg/kg and 5mg/kg) for five days. Subsequently, we performed biochemical analyses of blood serum and measured peroxidase and malondialdehyde (MDA) activity. Then, we performed histological sections to evaluate the brain's and liver's pathological and morphological changes. The data showed that the open field tests did not alter the locomotor activity. Furthermore, the elevated cross-maze tests showed no anxiety effect in the GO doses in the animals. The biochemical analyses indicated that GO influenced the level of biochemical parameters. Although, the oxidative stress assay showed an increase in peroxidase and MDA activity after GO intoxication. However, histopathological analysis of liver sections showed that GO caused liver inflammation, whereas, at the brain level, GO did not affect neuronal cells. The results indicate that GO caused toxic effects and that its toxicity could be mediated by oxidative stress.

Detection of Chlamydia sp. by fluorescence in situ hybridization (FISH) in histologic sections of the liver from exotic and native avian species

Chlamydiosis is a zoonotic disease that affects several animal species. Therefore, reliable detection techniques are essential for efficient control of the disease. Fluorescence in situ hybridization (FISH) for Chlamydia sp. was applied to 137 formalin-fixed, paraffin-embedded liver sections from native and exotic birds. The samples were divided into two groups: retrospective (n=57) and prospective (n=80). The probe was designed based on an annealing sequence that targets the Major Outer Membrane Protein coding gene. Livers previously confirmed for Chlamydia psittaci by polymerase chain reaction (PCR) and immunohistochemistry (IHC) were used as positive controls. Also, 47 randomly selected samples from the prospective group were submitted to PCR for Chlamydia psittaci for confirmation. From all 137 samples, 67% (92/137) were positive for Chlamydia sp. through FISH, from which 39% (36/57) and 61% (56/80) were from the retrospective and prospective groups, respectively. From the samples of the prospective group submitted for PCR confirmation, 83% (39/47) of them had a positive correlation with FISH results. When considering the number of targeted microorganisms per 400x field, 42,39% (39/92) of the samples had up to five microorganisms, 14,13% (13/92) had from six to ten, and 43,47% (40/92) of the samples had 11 or more microorganisms per field. FISH is a specific and reliable method to identify Chlamydia sp. in histologic sections of the liver, providing an additional tool for detecting avian chlamydiosis.

Detection of melatonin protective effects in sepsis via argyrophilic nucleolar regulatory region-associated protein synthesis and TLR4/NF-κB signaling pathway.

In this study, the protective effect of melatonin was investigated in lipopolysaccharide induced sepsis model. Twenty-eight rats were randomly divided: Control, Melatonin, LPS and LPS + Melatonin. After LPS application, surgically remove kidney and liver tissues. The level of malondialdehyde (MDA) an oxidative stress marker and the immunoreactivity of Toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), and transcription factor NF-κB were evaluated immunohistochemically. Expression levels for TLR4, TNF-α, NF-kB, IL-1β (interleukin 1 beta), and IL-6 (interleukin 6) were evaluated. Additionally, Argyrophilic NOR staining was performed in tissues. Vacuolization and inflammation were more intense in the kidney and liver sections in the LPS group compared to the other groups. It was observed that vacuolization and inflammation were decreased in LPS + Melatonin applied groups. It was determined that glomerular damage was increased in the LPS and LPS-melatonin groups, but the damage rate LPS-Melatonin group was decrease in the LPS group. It was determined that the MDA level in tissues of the LPS group was importantly increased compared to other groups. Additionally, TAA/NA ratio statistically significant differences were discovered between the groups. This study supports the potential protective effects of 10mg/kg melatonin by modulating critical markers of local immune reaction in a model of LPS-induced sepsis.

Effects of Lupinus luteus on hepatic and renal extracellular compounds turnover under diabetes in rat.

Hepatic and renal extracellular matrix (ECM) turnover associated with diabetes and potential beneficial effects of yellow lupin extract (YLE) need further investigations. The aim of this study was to explore the effect of yellow Lupinus luteus extract (YLE) on renal and hepatic ECM under diabetes. Composition of YLE performed by LC-ESI-MS. Diabetes (DM) was induced in rats by alloxan (250 mg/kg, ip). Normal and diabetic rats received 100 mg/kg of YLE for 1month. ECM was assessed by ELISA. Gelatinases and collagenases were analyzed by a colorimetric assay. Histology was performed on sections of liver and kidney. In the liver, diabetes increases collagen, laminin, and fibronectin contents, respectively, by 49% (p< .01), 56% (p< .01), and 67% (p< .05) compared to control rats. In the kidney, total collagen and laminin contents were increased by 91% (p< .01) and 35% (p< .01) in the DM group, while fibronectin content in diabetic animals and those treated with YLE remains similar to the control group. Collagenases and gelatinases activities were significantly increased by diabetes in liver and kidney. While YLE treatment abrogates diabetes-enhanced MMPs activitiesin liver. In diabetic rats, the liver shows signs of diffuse dilatation of the sinusoid veins and steatosis. However, the liver of diabetic rats treated with yellow lupine extract showed a normal histological aspect similar to controls. Diabetes causes hepatic and renal ECM turnover. YLE can be useful to partially improve tissue disorders induced by diabetes.

Histopathological Studies on the Effect of Taurine Against Etoposide-Induced Acute Liver and Kidney Toxicity in Female Albino Rats

Etoposide (ETP) is a topoisomerase Ⅱ (TOP Ⅱ) inhibitor and one of the leading chemotherapeutic drugs for treating a wide variety of tumors. However, ETP induced hepatotoxicity and nephrotoxicity limits its clinical use. This study aims to investigate the protective potential of taurine (Tau) to mitigated histopathological changes in the liver and kidneys of female albino rats treated with ETP. A total of 18 female rats were divided into three groups; control group, ETP-exposed group received intraperitoneal injection of ETP on the first 3 days of the study for a total cumulative dose of 44 mg/kg to induce hepatotoxicity and nephrotoxicity, ETP + Tau group received ETP as stated previously with 400 mg/kg/day of Tau via oral gavage for 15 days. Sections from the liver and kidney were evaluated under light microscope and ETP-exposed group revealed vascular congestion, chronic inflammatory cell infiltration predominantly lymphocytes, edema, vacuolar degeneration, atypical cells, pyknosis, and necrosis while liver and kidney sections of rats treated with combination of ETP + Tau group exhibited marked alleviation of the histopathological damage. The study concludes that treatment with ETP induced marked structural damages in the liver and kidney and such morphological damages are effectively diminished by administering Tau.

Study of Biochemical and Histological effects of fennel seeds (Foeniculum vulgare)on Liver in Male Rats

Consumption of foods enriched with herbs and herbal medicine products are highly popular. Their current popularity renders the assessment of their safety an urgent necessity, they must figure prominently in nutritional surveys as possible factors in cancer and some other diseases, as they may contain highly toxic chemicals and heavy metals in addition to natural organic toxins, made the present study aims to investigate the side effects of fennel seeds Foeniculum vulgare, in male rats, on the weights , histological changes and some of the physiological parameters of the liver.&#x0D; For this purpose, 60 Spargue-Dawley albino adult male rats were daily treated oraly with fennel seed powder mixed with rat diet in three different doses (50, 100, 200)gm/kg bodyweight(bw) in three different periods of time (10, 20, 30) days. Adult male rats were divided into 12 groups each of five rats, as following : (Group 1, 2, 3) normal control rats that were fed with chow pellet only for (10, 20, 30) days subsequently, (Group 4, 5, 6) experimental treated groups that respectively received fennel pellet in three doses of (50, 100, 200) gm/kg for 10 days, (Group 7, 8, 9) experimental treated groups that respectively received fennel pellet in three doses of (50, 100, 200) gm/kg for 20 days, (Group 10, 11, 12) experimental treated groups that respectively received fennel pellet in three doses of (50, 100, 200) gm/kg for 30 days.&#x0D; The end of each experiment was followed by weighing the animals, blood sample of each animal was collected by heart puncture then directly centrifuged and the serum was kept at -80 oC for biochemical analysis and some histological standards, the animals were dissected, then the liver was excised and fixed in neutral buffered 10% formalin for histological preparation.&#x0D; Increased doses of fennel consumption and treatment duration statistically caused:&#x0D; &#x0D; Highly significant (p&lt;0.01) decrement in liver weights of fennel treated groups ( 7, 8, 9, 10, 11, 12) in comparison to control groups.&#x0D; Highly significant increment (p&lt;0.01) in Glutamate oxaloacetate transaminase(GOT) and Glutamate pyruvate transaminase(GPT) serum levels in treated groups (5,6,7,8,9,10,11,12), while Alkaline phosphatase(ALP) serum levels showed significant increment (p&lt;0.05) in fennel treated groups (10, 11, 12) compared to the control groups.&#x0D; liver sections showed sinusoidal dilatation with mild degenerative, inflammatory cells infiltration, congestion in blood vessels and necrosis.&#x0D; &#x0D; Fennel, liver, doses, necrosis.

Protective Effects of Vitamin D3 on Male Rat’s Hepatic Cell Injured by Diclofenac, A Histopathological Study

This experiment aimed to study the protective effects of vitamin D3 on hepatic cells injured by Diclofenac. Twenty-one male rats, 8 to 12 weeks of age and in weight from 180 to 220 grams, were housed in a standard, pathogen-free environment in the “College of Veterinary Medicine, University of Fallujah,” given unrestricted access to standard rat water and food. Then the rats were divided into 3 groups (each group containing 7 rats): G1 control group (IM injection of distill water for 7 days), G2 Diclofenac only (7-day course of a 10 mg/kg IM injection of diclofenac), G3 received intramuscular injections of VD3 three times per week at a dose of 1000 IU/Kg, then a 7-day course of a 10 mg/kg IM injection of diclofenac. Liver histological sections of the normal control (G1) showed no histopathological changes, while the histopathological sections of the liver of G2 exhibit hydropic degeneration, blood vessels congestion and inflammatory cell infiltration, Liver sections of G3 presented blood vessels congestion and mild inflammatory cell infiltration. This study concluded that VD3 can decrease the liver damage caused by diclofenac

Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model.

Background Hepatocellular carcinoma (HCC) can explicate about 90% of the total primary liver cancer cases, with approximately 800,000 new cases identified each year worldwide. In addition, any changes in the expression of the tumor necrosis factor α (TNF-α) type 1 receptor (TNFR1) might impact many biological processes, which may lead to cancer. Aims We conducted the following study to investigate the ability of CAY10500, a TNF-α inhibitor that prevents binding to the TNF receptor 1, to produce anticancer effects against hepatocellular carcinoma experimentally induced in rats and to discover its effect on nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Materials and methods HCC was induced in rats via 200 mg/kg thioacetamide followed by treating some rats with IV 1 mg/kg CAY10500. Assessment of the liver impairment was by measuring the serum α-fetoprotein (AFP) and investigation of liver sections stained with hematoxylin/eosin. The hepatic expression of both the messenger RNA (mRNA) and protein levels ofTNF-α, TNFR1, Nrf2, and HO-1 was assessed. Results We found that CAY10500 increased the survival percent of rats associated with a reduction in serum AFP and the number of hepatic nodules. Besides, CAY10500 reduced the expression of TNFR1 without affecting the expression of TNF-α. Finally, CAY10500 increased the expression of both Nrf2 and HO-1. Conclusions Inhibition of TNFR1 expression in HCC by using CAY10500 produced therapeutic effects as indicated by increasing the survival rate, reducing the serum AFP level, decreasing liver nodules, and improving hepatocytes' structure. In addition, TNFR1 significantly enhanced the expression of Nrf2 and HO-1.

Protective Effects of Black Tea (&lt;i&gt;Camellia sinensis&lt;/i&gt;) Extract on Endosulfan Induced Oxidative Stress, Inflammation and Hepatic Damage in Rats

With the agricultural expansion the use of pesticides is increasing rapidly in developing countries. Endosulfan, an organochlorine insecticide, is a broadspectrum effective compound used in wide variety of agricultural crops but known to generate free radicals in the liver and caused hepatotoxicity. Thus, we considered it necessary to explore the protective effect of black tea extract against endusulfan mediated hepatotoxicity. 18 male albino Wistar rats were divided into 3 groups: Control, endosulfan treated (5mg/kg body weight/day) and endosulfan+black tea extract treated (1ml of 2.5gm%/100gm of body weight/day). After 30 days of treatment period, all the animals were sacrificed, and blood and liver tissue were collected. Serum and tissue cholesterol, serum liver function parameters, liver oxidative stress parameters and serum proinflammatory cytokines were measured. Liver sections were stained with haematoxylene and eosine and histological evaluation was done. Results revealed that endusulfan induces oxidative stress in liver by altering oxidant/antioxidant balance, and causes inflammation resulting into hepatic damage. Black tea extract supplementation shows considerable protection against endosulfan mediated changes in liver. Thus, black tea extract exerts ameliorative effect against endosulfan mediated liver toxicity.