Histopathological Analysis Of Liver Tissue Research Articles

Helicobacter pylori components increase the severity of metabolic syndrome and its hepatic manifestations induced by a high fat diet

The metabolic syndrome, often accompanied by hepatic manifestations, is a high-risk factor for developing cardiovascular disease. Patients with metabolic dysfunction associated with steatohepatic disease (MASDL) are at significant risk of developing coronary artery disease. Atherosclerosis is a systemic inflammatory disorder in which several factors, including dietary or infectious factors, can cause an inflammatory response. Helicobacter pylori (HP) bacteria have been implicated in the progression of proatherogenic vascular endothelial lesions, moreover, our previous study in an experimental in vivo model of Cavia porcellus showed that HP components and high-fat substances acted synergistically in promoting vascular endothelial inflammation, leading to an early onset of a proatherogenic environment. In the present study, our goal was to determine the contribution of HP components to the development of hepatic manifestations of metabolic syndrome in an experimental model. Our results showed that HP infection in animals exposed to a high-fat diet increased oxidative stress and lipid peroxidation, followed by endothelial lipid deposition, impaired endothelial apoptosis, cell lysis, and increased vascular stiffness. Finally, histopathological analysis of liver tissue showed signs of MASLD development in HP-infected animals fed a high-fat diet.

Effectiveness of cannabidiol (CBD) on histopathological changes and gene expression in hepatocellular carcinoma (HCC) model in male rats: the role of Hedgehog (Hh) signaling pathway.

The third most prevalent malignancy to cause mortality is hepatocellular carcinoma (HCC). The Hedgehog (Hh) signaling pathway is activated by binding to the transmembrane receptor Patched-1 (PTCH-1), which depresses the transmembrane G protein-coupled receptor Smoothened (SMO). This study was performed to examine the preventative and therapeutic effects of cannabidiol in adult rats exposed to diethyl nitrosamine (DENA)-induced HCC.A total of 50 male rats were divided into five groups of 10 rats each. Group I was the control group. Group II received intraperitoneal (IP) injections of DENA for 14 weeks. Group III included rats that received cannabidiol (CBD) orally (3-30mg/kg) for 2weeks and DENA injections for 14 weeks. Group IV rats received oral CBD for 2weeks before 14weeks of DENA injections. Group V included rats that received CBD orally for 2weeks after their last injection of DENA. Measurements were made for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and alpha fetoprotein (AFP). Following total RNA extraction, Smo, Hhip, Ptch-1, and Gli-1 expressions were measured using quantitative real-time polymerase chain reaction (qRT-PCR). A histopathological analysis of liver tissues was performed.The liver enzymes, oxidant-antioxidant state, morphological, and molecular parameters of the adult male rat model of DENA-induced HCC showed a beneficial improvement after CBDadministration. In conclusion, by focusing on the Hh signaling system, administration of CBD showed a beneficial improvement in the liver enzymes, oxidant-antioxidant status, morphological, and molecular parameters in the DENA-induced HCC in adult male rats.

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.

Histopathological alteration in the liver of Sardinella longiceps as a biomarker of heavy metal pollution in aquatic ecosystem.

The discharge of heavy metals from industrial effluents into aquatic ecosystems is a major cause of serious aquatic pollution. The bioaccumulation of toxic heavy metals in aquatic species can lead to their transmission to the food chain, posing serious public health risks. Present study was done to assess heavy metal accumulation and histopathological analysis in the liver of Sardinella longiceps collected from Sassoon dock during the rainy season between 2019 to 2022. It was found that amongst studied heavy metals Cu, Cr, and Mn concentration was beyond the permissible limit of WHO and FAO guidelines. Histopathological analysis of liver tissues during the studied period showed various architectural alteration which could be due to the accumulation of heavy metals found in it.

An analysis of Heptoprotective effects of plant extract on albino rats by Deep Learning analysis using ResNet and VGG16 algorithms

The hepatoprotective and anti-inflammatory effects of Terminalia catappa L. and Pergularia daemia hydroalcoholic extracts in albino rats with CCl4-induced liver damage (HAETC and HAEPD, respectively). The extracts significantly reduced the harm induced by CCl4 when given orally at a dosage of 200mg/kg. They also showed strong hepatoprotective and antioxidant properties. Wistar albino rats in good health were divided into seven groups, each with six animals. Group I acted as the control and received no treatment, whereas Group II was given 30% CCl4 (1ml/kg, intraperitoneally) to cause hepatotoxicity. After administering Silymarin (25 mg/kg, orally) as per protocol, Group III underwent CCl4 therapy. The CCl4-induced rats showed significant reductions in antioxidant enzymes like SOD, catalase, glutathione peroxidase (GPX), and glutathione-S-transferase (GST), as well as increases in serum marker enzymes like SGOT, SGPT, alkaline phosphatase (ALK), ACP, LDH, and lipid peroxidation (LPO) activity. However, rats given HAEPD and HAETC showed significant improvements, returning these parameters to levels that are almost normal (P 0.001).The hepatoprotective and antioxidant benefits of Terminalia catappa L. (HAETC) and Pergularia daemia (HAEPD) against CCl4-induced hepatotoxicity in rats were further validated by histopathological analysis of liver tissues. It encourages the use of pre-trained CNN architectures, such as VGG16 and ResNet (Residual Network), in the proposed method, which uses convolutional neural networks (CNNs) for histopathological image analysis to assess the hepatoprotective properties of Pergularia daemia and Terminalia catappa L. leaf extracts against CCl4-induced hepatotoxicity. These well-known CNN models may be modified for precise and effective histopathological image interpretation, assisting in the evaluation of the impact of plant extracts on liver health.

Combinatorial impact of Chelerythrine and DADS in the restoration of liver physiology during carcinogenic exposure in mice (Mus musculus)

Investigation of the efficacy of the combined drugs chelerythrine and DADS in restoring chemically induced hepatocellular carcinoma in Swiss albino mice. 4-6 week-old mice were considered for experimentation. The genotoxic carcinogen para-induced liver cancer--dimethyl-amino azobenzene along with nongenotoxic promoter carcinogen phenobarbital exposure. During the study, animals were co-treated with 100mg/kg body weight DADS and 5mg/kg body weight chelerythrine individually or in combination for 120 days. Bioparametric enzymatic assays of ALT, AST, ALKP, and GGT were performed. The estimation of TBARS, analysis of bone marrow chromosomal abnormalities, sperm head anomalies, and histopathological tissue structure in the co-treated group followed studies. An increase in enzymatic activities of plasma ALT, AST, ALKP, and GGT was observed after carcinogen exposure. Individual treatment of chelerythrine and DADS restored the activities mentioned above to some extent, although combined drugs successfully maintained the enzymatic activities in plasma. Changes in bone marrow chromosomal morphology and sperm head anomalies after carcinogen exposure were prevented in the individual and, most significantly, after combined drug therapy. Histopathological analysis of liver tissue of both male and female mice also demonstrated the preservation of tissue structures in the treated group, most significantly in the combined treatment, even after PB+P-DAB exposure. Chelerythrine and DADS individually protected liver tissue to a certain extent from the tumorigenic toxic effect of PB+P-DAB exposure. The combination of DADS and chelerythrine successfully guarded the tissue from any corrosive, carcinogenic impact and thus instigated further consideration as an effective alternative therapy against chemically induced hepatocarcinoma.

The raw and vinegar-processed Curcuma phaeocaulis Val. ameliorate TAA-induced zebrafish liver injury by inhibiting TLR4/MyD88/NF-κB signaling pathway

Ethnopharmacological relevanceLiver injury, the main factor in the pathogenesis of most liver diseases, is a known contributor to acute liver failure, liver fibrosis, or liver cancer. Curcuma phaeocaulis Val. (PEZ) has been broadly used in treating liver injury with satisfying therapeutic effects; however, the mechanism is still unclear. Aim of the studyThis study aimed to explore the mechanism of PEZ in ameliorating thioacetamide (TAA)-induced zebrafish liver injury based on a comprehensive method integrating network-based computational prediction and experimental validations. Materials and methodsUltrahigh-performance liquid chromatography-quadrupole exactive mass spectrometry/mass spectrometry (UPLC-Q-Exactive MS/MS) analysis was used to analyze components in raw and vinegar-processed PEZ (VPEZ). Network pharmacology was used to construct a compound-target network for liver injury to predict the possible biological targets of PEZ along with potential signaling pathways. TAA-induced zebrafish larvae liver injury model was established, and the anti-liver injury effect of PEZ by a series of indexes was measured, including liver phenotype analysis, histopathological analysis of liver tissues, and biochemical indexes analysis. Remarkably, the predicted pathway by network pharmacology was further validated using RT-qPCR and Western blotting analyzes in animal experiments. Results40 chemical constituents derived from PEZ were identified, while 45 chemical components derived from VPEZ were identified. Based on it, 565 genes related to these identified compounds in PEZ and 1023 genes linked to liver injury were collected by network pharmacology. Critically, KEGG analysis indicated that the TLR4/MyD88/NF-κB signaling pathway was recommended as one of the main pathways related to the anti-liver injury effect of PEZ. Experimentally, PEZ could alleviate TAA-induced liver injury. Compared to the liver injury model group without any treatment, the treatment of PEZ significantly reduced the expression of both mRNA and protein targets in the TLR4/MyD88/NF-κB signaling pathway. In addition, the effect of VPEZ was more significant than that of the raw one. ConclusionThe raw and vinegar-processed PEZ could ameliorate TAA-induced zebrafish liver injury through TLR4/MyD88/NF-κB signaling pathway.

Evaluation of Subacute Toxicity of Hydroethanolic Extracts Combinations from <i>Gnetum africanum</i> (Welv.) and <i>Gnetum buchholzianum</i> (Engl.) (Genetaceae) Leaves: Two Botanical with Antiproliferative and Antioxidant Potential

This study was conducted to assess the toxic effect of hydroethanolic extract combinations of Gnetum africanum Welv. leaves and Gnetum buchholzianum Engl. (Gnetaceae) in experimental rats to test the validity of the treatment of liver disorders related to oxidative stress. The Combinations (m/m) 50-50 for E2 and 75-25 for E3 of ethanol-water extracts from plant leaves at the respective doses of 100, 200, and 400 mg/kg of body weight were used for 32-day toxicity. They were obtained after harvesting leaves, sorting, drying in the air cover for three weeks, and grinding. The resulting powder was doubly macerated with 70% ethanol for 48 hours and filtered. The filtrate was concentrated with the Heidolph-brand rotary rotavapor and each extract obtained was preserved. The administrations were carried out by gavage to wistar, male and non-pregnant female albino rats. In the end, the animals were sacrificed. The serum and organ homogenates were obtained for biochemical, tissue, and histopathological analyses respectively. The analyses revealed insignificant variations at the 5% probability threshold of the weight growth of experimental animals. These variations were found to be statistically significant at the same probability for biochemical and tissue parameters based on the dose of plant extracts and compared to control animals. Histopathological analysis of liver tissue showed leukodate infiltration that indicates extract-induced inflammation of the hepatocytes at the 400 mg/kg dose of body weight in females. However, this infiltration of the cells would have improved the regeneration of hepatocytes justified by the normal rate of transaminases. These results showed that combinations of hydroethanolic extracts of G. africanum and G. buchholzianumare non-toxicand may be potential candidates in the Cameroonian flora medicinal plant database shown in the monitoring of oxidative stress-related diseases.

PHYTOPHARMACOLOGICAL EVALUATION OF HYDROALCOHOLIC EXTRACT OF BARK OF PONGAMIA GLABRA VENT. FOR ANTI-OBESITY ACTIVITY AND EFFECT ON LIPID PROFILE AND HEPATIC ENZYMES

Pongamia glabra is a native Indian subcontinent as well as south-east Asia drug used widely in many herbal formulations. The bark extract is used in the present study to evaluate its anti-obesity activity and its effect on lipid profile and hepatic enzyme. In-vivo studies were done using high fat diet along with DPMA model. Anti-obesity Evaluations included in the study was analysis of serum biochemical parameters (Serum Lipid Profile), determination of atherogenic index and coronary risk, Determination of Adiposity Levels, Fat Depot and Liver weight/Body weight Ratio (%) and histopathological analysis of liver tissues and adipose tissues. The results of the present study suggested that in actute toxicity studies, animals did not show any mortality at the dose of 500 mg/kg;bw. The Pongamia glabra bark at the dose of 500 mg/kg body weight found to show strong reducing effect on serum TC, TG and LDL levels among the treatments. The atherogenic index and coronary risk index showed significant reduction when treated with hydroalcoholic extract of Pongamia glabra bark extract. A significant increase in Lee index was observed in rat fed with high fat dies. The study showed that Weight of different body fat depots i.e. epitdidymal, retroperitoneal, mesenteric fat depot and total fat were significantly increased in HFD group as compared to the normal control group of rat. The histopathological studies suggested that Pongamia glabra bark extracts suppress the enlargement of hepatocytes and the accumulation of vesicles in the hepatic tissues. The present study thus clearly indicates that Pongamia glabra stem bark has a significant anti-obesity effect which supports its traditional uses.

Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 Ameliorates Insulin Resistance in Palmitic Acid-Induced HepG2 Cells and High Fat Diet-Induced Mice.

The purpose of this study was to evaluate the capacity of Lactiplantibacillus plantarum MG4296 (MG4296) and Lacticaseibacillus paracasei MG5012 (MG5012) on insulin resistance (IR) and diabetes-related metabolic changes in palmitic acid (PA)-induced HepG2 cells and high-fat diet-induced mice. In vitro, cell-free extracts of MG4296 and MG5012 alleviated IR by increasing glucose uptake and glycogen content in PA-induced insulin-resistant HepG2 cells. In vivo, MG4296 and MG5012 supplementation markedly decreased body weight and glucose tolerance. Administration of both strains also improved serum glucose, glycated hemoglobin, insulin, triglyceride, LDL/HDL ratio, and homeostatic model assessment of IR (HOMA-IR). Histopathological analysis of liver tissue demonstrated a significant reduction in lipid accumulation and glycogen content. Moreover, MG4296 and MG5012 treatment enhanced phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) expression in the liver. Overall, MG4296 and MG5012 could prevent HFD-induced glucose tolerance and hyperglycemia by improving IR. Therefore, L. plantarum MG4296 and L. paracasei MG5012 could be useful as new probiotics candidates to improve T2DM.

Antioxidant and antimalarial properties of Sophora exigua Craib. root extract in Plasmodium berghei-infected mice

BackgroundSophora exigua Craib. is commonly used in Thailand to reduce fever and increase postpartum breast milk production in women who have hypogalactia. However, there has been no report on the antioxidant and antimalarial properties of this plant. This study aimed to investigate the antioxidant and antimalarial activities of S. exigua root extract and to evaluate its acute toxicity in mice to confirm its safety.MethodsThe in vitro antioxidant activities were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide radical, and hydroxyl radical scavenging assays. The in vivo antioxidant activities were determined by detecting the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the livers of malaria-infected mice. The in vivo antimalarial activity was determined by Peters’ 4-day suppressive test in mice infected with Plasmodium berghei ANKA and orally administered S. exigua root aqueous and ethanolic extracts at different doses (200, 400, and 600 mg/kg body weight). In addition, the acute oral toxicity of the plant extracts was assessed in mice at a dose of 2000 mg/kg body weight.ResultsThe ethanolic extract of S. exigua root exhibited inhibition of DPPH radicals, superoxide anions, and hydroxyl radicals, with half maximal inhibitory concentration (IC50) values of 24.63 ± 1.78, 129.78 ± 0.65, and 30.58 ± 1.19 μg/ml, respectively. Similarly, research on the in vivo antioxidant activity indicated that the ethanolic extract of S. exigua root exerted a stronger effect than the aqueous extract. The aqueous extract at doses of 200, 400, and 600 mg/kg had stronger antimalarial activity than the ethanolic extract. The aqueous extract at 600 mg/kg exhibited 60.46% suppression of parasitemia. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and blood urea nitrogen (BUN) were detected in the mice treated with 2000 mg/kg ethanolic extract, which was related to the results of histopathological analysis of liver tissue, showing ballooning degeneration of hepatocytes, diffuse hepatic hemorrhage, and infiltration of inflammatory cells.ConclusionsThis study demonstrated that the ethanolic S. exigua root extract possessed antioxidant properties, and the aqueous extract also had antimalarial activity. Therefore, this plant is an alternative source of new antioxidant and antimalarial agents.

Embelin from Embelia ribes ameliorates oxidative stress and inflammation in high-fat diet-fed obese C57BL/6 mice

Background: A safe, efficacious, and economical drug for the treatment of obesity is the need of the time. Literature published in previous years referred to embelin as a potential investigational therapeutic agent to manage obesity. Objectives: This study was designed to isolate and characterize embelin from Embelia ribes and further to assess its role in alleviating oxidative stress and chronic inflammation in the high-fat diet (HFD) fed obese C57BL/6 mice. Materials and Methods: Embelin extracted from berries of E. ribes with n-hexane by soxhlet extraction was characterized using high-performance thin-layer chromatography, infrared and liquid chromatography-mass spectrometry analyses. The obesity was induced by feeding of HFD for 8 weeks. Embelin (50 mg/kg/day, p.o.) was administered from 5th to 8th weeks along with HFD. After 8 weeks, the body weight gain and body mass index were calculated. Then, animals were sacrificed; serum and tissues were collected to further assess the various biomarkers of oxidative stress and inflammation. Results: The presence of embelin was confirmed using the above-mentioned analytical techniques. Treatment with Embelin showed amelioration of obesity biomarkers along with the substantial decline in levels of protein expression of nuclear factor erythroid 2-related factor and nuclear factor kappa-B in liver tissue. Treatment with embelin also normalizes the liver tissue levels of thiobarbituric acid reactive substances, glutathione, superoxide dismutase, and catalase. The histopathological analysis of liver tissue showed significant prevention of necrotic and inflammatory changes in embelin treated HFD fed mice. Conclusion: The results of the study clearly indicated the potential of embelin in ameliorating obesity by alleviating oxidative stress and inflammation induced by HFD in C57BL/6 mice.

Hepatoprotective Role of <i>Phlogacanthus thyrsiflorus </i>Nees as a Potential Iron Chelating Drug

Exceeding iron levels in the body get accumulated in the liver and other vital organs that induce oxidative stress in the affected areas , which is clinically diagnosed as “iron overload”. Present study was undertaken to investigate the role of Phlogacanthus thyrsiflorus Nees, an endemic species of North-east India, in ameliorating such diseased conditions. Our results indicate that the methanolic leaf extract of Phlogacanthus thyrsiflorus (PTME) exhibits excellent iron chelation and antioxidant activities in dose dependent manner in vitro. To understand the in vivo conditions, thirty six mice were divided into six groups which were treated with differing doses of PTME. Levels of serum markers ALT and AST significantly elevates during diseased conditions but PTME treated mice have shown a marked decrease in the group (S200) by 39.24 and 17.24%. On the contrary lowering levels of liver antioxidant enzymes (GST, GSH, SOD and CAT) indicates stress. But 200mg/kg b.w of PTME treated groups restored the enzyme to optimum levels. Morphological changes were observed through histopathological analysis of liver tissues and we found significant differences in them . PTME was found to be completely nontoxic in the in vivo treatment, suggesting its feasibility as a safe oral drug. The above study suggests that PTME contributed to its free radical scavenging and iron chelation activity; however, further studies are required for the assessment of the phytoconstituents and the pathways through which it act to treat iron-overload diseases.

Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity

A toxicity evaluation of two Keggin-type heteropolytungstates, K7[Ti2PW10O40]·6H2O and K6H[SiV3W9O40]·3H2O, with different inhibitory potencies toward acetylcholinesterase activity (IC50 values of 1.04×10−6 and 4.80×10−4mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24h and 14days. A histopathological analysis of liver tissue was carried out 14days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration-dependent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K6H[SiV3W9O40]·3H2O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.

HEPATOPROTECTIVE EFFECT OF TOFU PROCESSED FROM GERMINATED SOYBEAN ON CARBON TETRACHLORIDE INDUCED CHRONIC LIVER INJURY IN MICE

The hepatoprotective activities of silk tofu made from germinated and non germinated soybeans at different doses of feeding against CCl 4 induced hepatic cell toxicity in mice was investigated in this study. The heptatoprotective activity was analyzed by assessing the ratio of liver weight to body weight (L/B), the levels of serum alanine aminotransferase (ALT), total cholesterols (TC), the hepatic malondehydyde (MDA), protein carbonyl (PC) and vitamin C levels as well as the histopathological analysis of liver tissue. All types of silk tofu significantly reduced the L/B value; ALT activity, total cholesterol, hepatic MDA and PC levels, beside, liver vitamin C content increased compared to CCl 4 intoxicated mice. Silk tofu made from germinated soybeans expressed higher hepatoprotective activity as compared to silk tofu made from non germinated soybeans. Mice fed with silk tofu made from germinated soybeans at the dose of 0.4 g/g body weight/day displayed all biochemical parameters as well as the liver tissue histopathological analysis that were similar to that of normal mice and silymarin treated mice. It was suggested that tofu specially made from germinated soybeans expressed great hepatoprotective effect.

Efficacy of a traditional unani formulation Jawarish-e-Amla Sada against CCl4induced liver toxicity in Albino Wistar rats: Comparison with silymarin treatment

Background: Jawarish‑e‑Amla Sada (JAS); a polyherbal Unani formulation, is claimed as a potential hepatoprotective agent in traditional Unani medicine treatise. Aims and Objectives: Though, JAS has its composition recorded in ancient Unani texts, there have been minimal attempts to scientifically validate its hepatoprotective potential. The present work is an attempt to evaluate the hepatoprotective activity of JAS in vivo. Materials and Methods: CCl 4 intoxicated Albino Wistar rats were used to evaluate the hepatoprotective activity of JAS (0.7 g/kg and 1.0 g/kg, p.o.) and the results were compared with, silymarin. The efficacy was established on the basis of altered levels of biochemical markers and histopathological analysis of the liver tissue. Results and Discussion: Treatment with the aqueous slurry of JAS significantly reduced the level of biochemical markers in CCl 4 intoxicated rats. These findings were well-supported by the histopathological analysis of liver tissue. The effect shown by JAS was found to be at par with silymarin treatment. Conclusion: This study suggests that CCl 4 induced liver damage can be ameliorated by traditional Unani formulation JAS. This justifies the traditional claim of JAS being a hepatoprotective agent.

Development of an Anti-Atherosclerotic Polyherbal Formulation: GSTC3.

A polyherbal formulation consisting of different proportions of Commiphora mukul (Hook ex Stocks) Eng., Salacia reticulata Wight, Terminalia arjuna (Roxb.) Wight & Arn, and Curcuma longa Linn extracts was tested for free-radical scavenging and anti-lipid peroxidative effects on serum and platelets in vitro. The most active formulation (GSTC3) was evaluated for its hypolipidemic potential on a high-fat, high-cholesterol diet (HFD) fed to male Wistar rats for a period of 45 days. At a dose of 100 mg/kg body weight, GSTC3 decreased serum total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and phospholipids similar to standard atorvastatin while maintaining high-density lipoprotein (HDL) at normal levels. Significantly lower levels of thiobarbituric acid-reactive substances (TBARS) were observed in both the liver and sera of rats treated with GSTC3. Although the phospholipid levels in liver remained unchanged, lower values of LDL, VLDL, and atherogenic index of plasma as well as higher HMG-CoA/ mevalonate ratios suggested a significant hypolipidemic effect for GSTC3, possibly by partial inhibition of HMG-CoA reductase activity. The histopathological analysis of liver tissue did not reveal lipid accumulation or indicate tissue damage. Overall, the results of this study suggest the hypolipidemic and anti-atherogenic efficacy of a nontoxic herbal formulation.

Influence of dietary supplementation of propolis on hematology, biochemistry and lipid profile of rats fed high cholesterol diet

The objective of the present study was to monitor the hypolipidemic and hypocholesterolemic effects of propolis in rats fed high cholesterol diet. The rats (n=32) were divided into four equal groups. The rats of group 1 (control) were fed basal diet, whereas rats of group 2 were fed basal diet mixed with cholesterol (1%). The rats of group 3 and 4 were fed high cholesterol diet (1%) mixed with propolis powder 1 and 2%, respectively. Hematological parameters were comparable among all groups. Cholesterol, triacylglycerol and ALT activities were increased significantly in rat fed high cholesterol diet as compared to control. Inclusion of propolis in high cholesterol diets reduced these parameters in serum. Hematological and biochemical findings were supported by histopathological analysis of liver tissues. Conclusively, 1% propolis was found as safe and enough to induce beneficial hypolipidemic and hypocholesterolemic effects in serum of rats fed high cholesterol diet.

Differential expression in ACE2, Ang(1-7) and Mas receptor during progression of liver fibrosis in a rat model

To investigate the changes in expression of the ACE2/Ang(1-7)/Mas receptor axis' components that occur during progression of liver fibrosis using a rat model system. Thirty-six adult male Wistar rats, were randomly assigned to groups of normal control (n = 6; no manipulation) and liver fibrosis (n = 30; given a subcutaneous injection of 40% chronic carbon tetrachloride (CCl4)). At post-injection days 15, 30, 45, 60 and 75, 1 control rat and 6 modeled rats were sacrificed for analysis. Histopathological analysis of liver tissue was performed with hematoxylin-eosin and rapid Masson staining. Protein expression level of Ang(1-7) was determined by enzyme-linked immunosorbent assay, and of ACE2 and Mas receptor was evaluated by immunohistochemistry. Real-time PCR was used to measure the mRNA expression levels of ACE2 and Mas receptor. The expression levels of ACE2, Ang(1-7) and Mas receptor showed a statistically significant upward trend that followed the progression of fibrosis up to post-injection day 60 (P less than 0.01), but the significant increase was not seen from day 60 to day 75. Each component of the ACE2/Ang(1-7)/Mas receptor axis shows differential expression during the development of liver fibrosis and may contribute to disease progression.

Human liver stem cells improve liver injury in a model of fulminant liver failure

Liver transplantation is currently the only effective therapy for fulminant liver failure, but its use is limited by the scarcity of organs for transplantation, high costs, and lifelong immunosuppression. Here we investigated whether human liver stem cells (HLSCs) protect from death in a lethal model of fulminant liver failure induced by intraperitoneal injection of D-galactosamine and lipopolysaccharide in SCID mice. We show that injection of HLSCs and of HLSC-conditioned medium (CM) significantly attenuates mouse mortality in this model. Histopathological analysis of liver tissue showed reduction of liver apoptosis and enhancement of liver regeneration. By optical imaging we observed a preferential localization of labeled HLSCs within the liver. HLSCs were detected by immunohistochemistry in large liver vessels (at 24 hours) and in the liver parenchyma (after day 3). Fluorescence in situ hybridization analysis with the human pan-centromeric probe showed that positive cells were cytokeratin-negative at 24 hours. Coexpression of cytokeratin and human chromosome was observed at 7 and, to a lesser extent, at 21 days. HLSC-derived CM mimicked the effect of HLSCs in vivo. Composition analysis of the HLSC-CM revealed the presence of growth factors and cytokines with liver regenerative properties. In vitro experiments showed that HLSC-CM protected human hepatocytes from apoptosis and enhanced their proliferation. These data suggest that fulminant liver failure may potentially benefit from treatment with HLSCs or HLSC-CM.