Serum Liver Function Parameters Research Articles

Hepato-protective Effect of Costus afer (Okpete) Juice Extract on Alcohol-induced Liver Toxicity in Adult Female Wistar Rats

Background: The oral intake of alcohol has become a widespread concern due to its high risk to body health. Therefore, our purpose in this study was to reveal the antioxidant efficacies of natural Costus's afer stem juice extract on hepatotoxicity induced by ethanol in adult female wistar rats. Methods: We examined the impacts of liver toxicity, were the experimental animals were given 1ml of 10% ethanol daily for 21 days, thereafter, C. afer was administered to evaluate its ameliorative effect in the female albino wistar rats orally treated with C. afer juice extract (200 and 400 mg/kg) for 7days. The rats were divided into four (4) groups; Group A served as the control group, which was given rat chow and water only. Groups B, C and D were given 1ml of 10% ethanol. Afterwards, groups C and D were treated with 200 and 400 mg/kg using 1ml and 2ml of the juice extract of C. afer, respectively. A liver function test and histological analysis were carried out. Results: The results showed that treatment with C. afer after the oral consumption of ethanol caused elevation in serum liver function parameters (alanine transferases, aspartate transaminase, and alkaline phosphate), which is significant compared to the control group. There was also a slight restoration in histopathological changes in the liver, as revealed by decreased areas of inflammation. Conclusion: The therapeutic efficiency of C. afer juice extract could be due to traces of anti-inflammatory properties and the ROS-scavenging agent. Our findings prove that the elevation of liver function markers by C. afer enables hepatic tissue to suppress inflammatory and oxidative mechanisms, resulting in enhanced liver structure and function. Therefore, C. afer extract is a protective and therapeutic supplement against toxic agents.

Effect of Inhalation Exposure to Nano-Imidacloprid on Liver and Kidney Functions In Male Rats

Pesticide poisoning is a serious global public health issue and is responsible for a sizable number of annual fatalities. This study was designed to examine the potentially harmful effects of adult rats being exposed to imidacloprid (IMD) as a nanoparticle by determining the chronic effect of inhalation of (5,10 and 20) mg/kg/b.w. of nano-imidacloprid for a duration of 60 days. The most important biochemical parameters of the serum liver function parameters were aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ALP, kidney function [blood urea, creatinine, and urea], and oxidative stress parameters (MDA, GSH, and CAT) in all treated groups when compared to the control group. The exposure caused a highly significant decrease (P≤0.05) for (AST) and (ALT). No significant changes were observed, while a highly significant decrease was recorded for (ALP) in all treatments with nano-imidacloprid compared with the control. On the other hand, a highly significant decrease in blood urea, creatinine, and uric acid was recorded in all groups treated with nano-imidacloprid compared with the control. Oxidative stress parameters revealed a highly significant (P≤0.05) increase in malondialdehyde (MDA) after 60 days of exposure and a decline in reduced glutathione (GSH) and catalase activity CAT.

Dapagliflozin alleviates arsenic trioxide-induced hepatic injury in rats via modulating PI3K/AkT/mTOR, STAT3/SOCS3/p53/MDM2 signaling pathways and miRNA-21, miRNA-122 expression

Dapagliflozin (DPG) is a sodium-glucose co-transporter 2 inhibitor that is commonly used in the treatment of type 2 diabetes. However, studies have shown that DPG has a protective effect under a variety of experimental conditions through its antioxidative and anti-inflammatory properties. DPG's effect on experimental hepatotoxicity caused by arsenic trioxide (ATO) has yet to be investigated. The purpose of this study was to investigate the protective effect of DPG in preventing hepatic damage caused by ATO and discover the underlying mechanisms. The effect of DPG (1 mg/kg, orally) on ATO (5 mg/kg, i.p.)-induced hepatic injury was evaluated in rats. Serum liver function parameters, as well as oxidative stress biomarkers and inflammatory cytokine levels were assessed. Histopathological changes in the liver were detected using H&E staining. Using Western blotting and PCR techniques, the molecular mechanisms of DPG in ameliorating hepatic injury were investigated. DPG improved liver function by inhibiting histopathological changes, decreasing levels of hepatic function and toxicity parameters measured in both serum and tissues, and exhibiting antioxidant and anti-inflammatory effects, according to the findings. Consistent with the PCR results, DPG also decreased the expression of LC3-II, micro-RNA-122, and micro-RNA-21 while increased the expression of SOCS3. Furthermore, according to western blotting results, DPG was able to reduce the protein expression of AKT, mTOR, PI3K, and STAT3. Although further clinical research is necessary, this study highlights the potential of DPG in preventing liver damage in a rat model of hepatotoxicity induced by ATO.

Indocyanine green clearance predicts outcome in patients undergoing transcatheter valve intervention for severe atrio-ventricular valve regurgitation.

Severe mitral regurgitation (MR) and tricuspid regurgitation (TR) aggravate haemodynamic stress leading to congestive heart failure with impaired hepatic function, also known as cardiohepatic syndrome (CHS). Current perioperative risk calculators do not sufficiently consider CHS and serum liver function parameters lack sensitivity to diagnose CHS. Indocyanine green and its elimination (measured by the LIMON® test) represent a dynamic and non-invasive test which correlates with the hepatic function. Nevertheless, its utility in the setting of transcatheter valve repair/replacement (TVR) to predict CHS and outcome remains unknown. We analysed liver function and outcomes of patients undergoing TVR for MR or TR between August 2020 and May 2021 at the Munich University Hospital. Out of a total of 44 patients treated at the University Hospital of Munich, 21 (48%) were treated for severe MR, 20 (46%) for severe TR and 3 (7%) for both diseases. Procedural success defined as MR/TR ≤2+ was 94% among MR patients and 92% among TR patients. While classical serum liver function parameters did not change after TVR, there was a significant improvement in liver function as assessed by the LIMON® test (P ≤ 0.001). Patients with baseline indocyanine green plasma disappearance rate <12.95%/min showed significantly increased 1-year mortality (hazard ratio: 1.54, 95% confidence interval: 1.05-2.25, P = 0.027) and lower New York Hear Association class improvement (P = 0.05). Especially in the context of the recently stressed importance of a careful patient selection prior to the interdisciplinary treatment of valvular heart disease, the LIMON® test may provide further real-time information on the patients' cardiohepatic injury and prognosis.

Investigating the hepatoprotective potentiality of marine-derived steroids as promising inhibitors of liver fibrosis.

It has been reported that organic extracts derived from soft corals belonging to the genus Sarcophyton have exhibited a wide range of therapeutic characteristics. Based on biochemical and histological techniques, we aimed to assess the hepatoprotective role of the organic extract and its principal steroidal contents derived from the Red Sea soft coral Sarcophyton glaucum on acetaminophen-induced liver fibrosis in rats. Serum liver function parameters (ALT, AST, ALP and total bilirubin) were quantified using a spectrophotometer, and both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels were determined by using enzyme-linked immunosorbent assay (ELISA) kits while transformed growth factor beta (TGF-β) and tumor necrosis factor α (TNF-α) in liver tissue homogenate were determined using ELISA, and TGF-β and TNF-α gene expression in liver tissue was determined using real-time PCR following extraction and purification. Histopathological alterations in hepatic tissue were also examined under a microscope. In order to prioritize the isolation and characterization of the most promising marine steroids from the organic extract of the Red Sea soft coral Sarcophyton glaucum as hepatoprotective agents, a computational approach was employed. This approach involved molecular docking (MDock) and analysis of the structure-activity relationship (SAR) against glutathione-S-transferase (GST) and Cu-Zn human superoxide dismutase (Cu-ZnSOD) enzymes. Although the major role in the detoxification of foreign chemicals and toxic metabolites of GST and SOD enzymes is known, there is a lack of knowledge about the mode of action of the hepatoprotective process and those of the targets involved. The present study investigated the multiple interactions of a series of marine steroids with the GST and SOD enzymes, in order to reveal insights into the process of hepatoprotection.

Effect of wheat germ oil on phenylhydrazine-induced toxicity in male albino rats

Wheat germ oil (WGO) is a natural source of antioxidant such as glucosylated hydroquinones, tocopherols and it is an excellent source of polyunsaturated fatty acids. The point of the present study is to see how efficient is the WGO against phenylhydrazine (PHZ) induced hemotoxicity in rats. Rats were divided into five groups (six rats each); control group (normal rats), WGO group (administrated by daily oral dose of WGO, 300 mg/kg b.w.), PHZ group (injected intraperitoneally with a daily dose of PHZ, 60 mg/kg b.w. for 3 consecutive days), treated group (injected with PHZ then after 3 days administered by WGO) and protective group (administrated daily by WGO for 11 days then injected with PHZ). The experimental trial was continued for a total period of 14 days. The results showed that the PHZ induced significant decreases in hematological parameters (RBCs, Hb, Hct, PLT), serum proteins (total protein, albumin and globulin) and antioxidant enzymes (CAT, GPX and SOD) activity and significant increases in white blood cells (WBCs), erythropoietin hormone, serum ferritin level, serum liver function parameters (ALT, AST, TBIL and ALP), serum kidney function parameters (creatinine, urea and uric acid) and malondialdehyde (MDA) content. Administration of WGO improved the hematological parameters, erythropoietin hormone, ferritin level, serum proteins, liver function enzymes, kidney function parameters, antioxidant enzyme activities and MDA content in rats injected with PHZ. In conclusion, the results of the present study revealed that the WGO has a therapeutic and protective roles in improving the hemolytic anemia and toxicity induced by PHZ.

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.

Effect of Natural Commiphora myrrha Extract against Hepatotoxicity Induced by Alcohol Intake in Rat Model.

The oral intake of alcohol has become a widespread concern due to its high risk to body health. Therefore, our purpose in this study was to reveal the antioxidant efficacies of natural Commiphora myrrha on hepatotoxicity and oxidative stress induced by ethanol in adult male rats, especially because these were not adequately revealed by previous studies. We examined the impacts of C. myrrha in male Sprague Dawley rats orally treated with C. myrrha (500 mg/kg) alone or in combination with 40% ethanol (3 g/kg), daily for 30 days. The results showed that treatment with C. myrrha after the oral consumption of ethanol caused a reduction in serum liver function parameters (alanine transferases, aspartate transaminase, and total bilirubin), hepatic tumor markers (α-L-flucosidase and arginase), and hepatic lipid peroxidation indicator (thiobarbituric acid reactive substances), as well as a slight restoration (not significant) in the levels of superoxide dismutase, catalase, reduced glutathione; and total antioxidant capacity. In addition, it alleviated histopathological changes in the liver, as revealed by decreased areas of inflammatory infiltrate, milder necrosis, and noticeably reduced periportal fibrosis and hemorrhage. The therapeutic efficiency of C. myrrha could be due to its rich sesquiterpenoids content which possesses anti-inflammatory properties and ROS-scavenging activities. Our findings provide evidence that the attenuation of oxidative stress by C. myrrha enables hepatic tissue to suppress inflammatory and oxidative mechanisms, resulting in enhanced liver structure and function. Therefore, C. myrrha extract shows promise as a protective and therapeutic supplement against toxic agents.

Galectin-3 inhibition retained expression of hepatocyte nuclear factors 4α and 1α in acetaminophen induced acute liver injury

Introduction: Hepatocyte nuclear factors HNF4α and HNF1α, key transcription factors that regulate drug metabolism enzymes expression, were linked to inflammation. Galectin-3 (Gal-3) is a multi-role animal lectin which is involved in inflammation. This study aims to evaluate the impact of galectin-3 inhibition, by using modified citrus pectin (MCP), on HNF4α and HNF1α gene expression levels after acetaminophen (APAP) induced acute liver injury in Wistar rats. Materials and Methods: Sixty-four male Wistar rats were divided into four groups as follows; control, MCP, APAP and MCP plus APAP administered groups. The groups received APAP were divided into three subgroups each; in which rats were sacrificed after 24, 48 and 72 hours (h) from APAP administration. Expression levels of HNF4α and HNF1α, beside levels of Gal-3, tumor necrosis factor- α (TNF-α), Cytochrome P450 2E1 (CYP2E1), reduced glutathione (GSH), glutathione reductase (GR) and peroxidase (GPx) activities, liver function parameters were evaluated, along with histopathological study of the liver. Results: APAP high dose induced inhibition of liver HNF4α and HNF1α gene expression, CYP2E1 and GSH levels, GR and GPx activities, and increased hepatic Gal-3, TNF-α and serum liver function parameters levels, besides inducing hepatic necrosis. The toxic effects were stronger after 24 h then declined gradually after 48 h and 72 h. Inhibiting Gal-3 functionality after APAP high dose administration reduced TNF-α level and retrieved liver levels of HNF4α and HNF1α expression, CYP2E1, GSH, GR and GPx closer to normal control levels. Conclusion: Inhibiting Gal-3 functionality affects HNF4α and HNF1α gene expression levels and reduced inflammation after APAP high dose administration.

Effect of Biochemical Parameters and Histology of Liver on Sucrose-Induced Metabolic Syndrome in Wistar Rats

Introduction: Metabolic syndrome (MetS) is a multiple factorial condition that draws a parallel to various risks such as dyslipidemia, hypertension, and hyperglycemia. As per the new International Diabetes Federation (IDF), for a person to be defined as having metabolic syndrome of central obesity along with any two of the following four factors: Raised triglycerides (≥ 150 mg/dL), reduced HDL cholesterol (&lt;40 mg/dL in males and&lt;50 mg/dL in females), raised blood pressure (systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg) and raised fasting plasma glucose (FPG ≥ 100 mg/dL).&#x0D; Sucrose is a common sugar, also known as “table sugar”. It is a sweet-tasting carbohydrate that is present in almost everything we eat. It is a natural compound that gives us valuable energy as it is a quick and easy source of energy but sucrose tends to be harmful when over-consumed. Sucrose is consumed worldwide and it is known to have harmful effects on metabolic heath.&#x0D; Aim: The aim of this study was to determine the histological and biochemical changes of liver in sucrose induced metabolic syndrome in Wistar rats.&#x0D; Methods: Total of 24 Wistar rats were randomly grouped into three groups A, B and C. 10g of sucrose was weighed and dissolved in 100 ml of distilled water to make the 10% sucrose solution and 20g was also weighed and dissolved in 100 ml of distilled water to make the 20% sucrose solution. Group A served as control and was administered orally with distilled water, group B was administered with the 10% sucrose solution orally and group C was administered with the 20% sucrose solution orally all for 6 weeks (42 days) The Wistar rats were anaesthetized using chloroform vapour in an enclosed transparent jar. Blood was collected through cardiac puncture and dispensed in to plain container for liver biochemical analysis and liver was carefully removed and washed with normal saline and then fixed in 10 % formol saline for histological preparation.&#x0D; Results: There was increase in some serum liver function parameters: total protein (TP), Albumin (ALB), Total bilirubin (TB), Aspartate transaminase (AST) and Alanine transaminase (ALT) but the increase was statistically insignificant. Malondialdehyde (MDA), Triglycerides (TG), High density lipoprotein- cholesterol (HDL-Chol) and Glucose parameters were also statistically insignificant. Histopathology examination of sections of the liver specimens shows steatosis (deposits of fat on the liver) on the liver of both group B and C Wistar rats.&#x0D; Conclusion: Histological examination of the liver specimens shows presence of fat cells deposition (steatosis) in all liver sections. Further studies needed to make a definitive conclusion as to whether the biochemical parameters can cause insignificant or significant changes.

Cichotyboside, A Sesquiterpene Glycoside from Cichorium intybus Attenuates Carbon Tetrachloride-Induced Liver Injury in Rat

Aims: Cichorium intybus L. is traditionally used for the management of the various liver disorders and also widely scientifically reported for hepatoprotection. The present study aims at investigating cichotyboside, bioactive sesquiterpene glycoside, from seeds for hepatoprotective effect against carbon tetrachloride (CCl₄) following isolation and characterization. Methods: Cichotyboside was isolated from C. intybus seeds and characterized by infrared spectroscopy (IR), liquid chromatography-mass spectrometry (LC/MS), and carbon 13 nuclear magnetic resonance (¹³C NMR). High-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC) have been developed for the standardization of Cichotyboside. In this study, biochemical assays, liver functional capacity restoration regarding drug metabolism, antioxidant potential, and histological staining were applied to evaluate the anti-hepatotoxic efficacy of cichotyboside on a carbon tetrachloride induced liver injury in rats. Results: The results showed that cichotyboside could significantly attenuate the pathological changes, increase the levels of hepatocyte repair, and regulate oxidative damage. Hepatoprotective activity of cichotyboside is indicated by its ability to decrease thiopental induced sleeping time, increased BSP clearance, reverse effect of CCl₄ on the body weight, relative liver weight, serum liver function parameters, histopathology and activity of liver antioxidant enzymes. Conclusion: Cichotyboside exerts hepatoprotective activity against the CCl₄ induced toxicity, possibly by its remarkable antioxidant potential, reversing the impaired metabolisms and repairing the fatty changes in hepatocytes.

Effect of galectin-3 inhibition on hepatocyte nuclear factors 4α and 1α expression in liver after acetaminophen long-term induced toxicity.

Acetaminophen (APAP) induced liver injury can occur through acute or repeated administration of high doses. Hepatocyte nuclear factors HNF4α and HNF1α are key transcription factors involved in regulating the expression of drug metabolism enzymes and are affected by proinflammatory cytokines. Meanwhile galectin-3 (Gal-3) is a β-galactoside-binding lectin implicated in the regulation of macrophage activation and secretion of inflammatory mediators. This study aimed to evaluate the impact of galectin-3 inhibition on HNF4α and HNF1α gene expression after long-term administration of APAP, and to investigate the resulted effect on APAP induced hepatotoxicity. The study was performed on thirty two Wistar rats divided equally into four groups; control group, modified citrus pectin (MCP) (Gal-3 inhibitor) receiving group, APAP receiving group, and APAP plus MCP receiving group. APAP induced inhibition of liver HNF4α and HNF1α gene expression, and elevation of liver Gal-3 and tumor necrosis factor- α levels (TNF-α), depletion of reduced glutathione and its maintaining enzymes, besides elevation in levels of serum liver function parameters and appearance of necrotic areas in the liver. Gal-3 inhibition preserved HNF4α and HNF1α gene expression, TNF-α, and each of reduced glutathione and its maintaining enzymes near normal levels. It also significantly reduced APAP induced hepatotoxicity.

Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation.

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT).Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.

Hepatoprotective effect of Moringa oleifera extract on TNF-\u03b1 and TGF-\u03b2 expression in acetaminophen-induced liver fibrosis in rats

BackgroundIt has been reported that Moringa oleifera (MO) has different medicinal properties. The aim of this study was to evaluate the hepatoprotective role of Moringa oleifera extract on acetaminophen-induced liver fibrosis in albino rats on a biochemical and histological basis. Forty male albino rats were divided into four groups: group I (control group), healthy rates; group II (acetaminophen group), rates received acetaminophen for induction of liver fibrosis; group III (treated group), liver fibrosis of rates treated with Moringa oleifera extract; and group IV (prophylactic group), rates treated with Moringa oleifera extract before and after induction of liver fibrosis. Serum liver function parameters were quantified using a spectrophotometer, while tumor necrosis factor α (TNF-α) and transformed growth factor beta (TGF- β) in liver tissue homogenate by means of enzyme-linked immunosorbent assay (ELISA), and expression of liver tissue TNF-α and TGF-genes was measured by real-time PCR after extraction and purification. Hepatic tissue was also evaluated under a microscope for histopathological changes.ResultsOur results showed a significant decrease in liver enzymes, TNF-α, and TGF-β in the treated and prophylactic groups compared to the acetaminophen group, and our biochemical data were consistent with the histopathological findings confirming the hepatoprotective effect of Moringa oleifera extract.ConclusionsBiochemical parameters and histopathology results provide evidence that Moringa oleifera ethanolic extract has a great potential to prevent and improve liver damage due to its protective activity.

Reduced Chronic Toxicity and Carcinogenicity in A/J Mice in Response to Life-Time Exposure to Aerosol From a Heated Tobacco Product Compared With Cigarette Smoke.

We conducted an inhalation study, in accordance with Organisation for Economic Co-operation and Development Test Guideline 453, exposing A/J mice to tobacco heating system (THS) 2.2 aerosol or 3R4F reference cigarette smoke (CS) for up to 18 months to evaluate chronic toxicity and carcinogenicity. All exposed mice showed lower thymus and spleen weight, blood lymphocyte counts, and serum lipid concentrations than sham mice, most likely because of stress and/or nicotine effects. Unlike THS 2.2 aerosol-exposed mice, CS-exposed mice showed increased heart weight, changes in red blood cell profiles and serum liver function parameters. Similarly, increased pulmonary inflammation, altered lung function, and emphysematous changes were observed only in CS-exposed mice. Histopathological changes in other respiratory tract organs were significantly lower in the THS 2.2 aerosol-exposed groups than in the CS-exposed group. Chronic exposure to THS 2.2 aerosol also did not increase the incidence or multiplicity of bronchioloalveolar adenomas or carcinomas relative to sham, whereas CS exposure did. Male THS 2.2 aerosol-exposed mice had a lower survival rate than sham mice, related to an increased incidence of urogenital issues that appears to be related to congenital factors rather than test item exposure. The lower impact of THS 2.2 aerosol exposure on tumor development and chronic toxicity is consistent with the significantly reduced levels of harmful and potentially harmful constituents in THS 2.2 aerosol relative to CS. The totality of the evidence from this study further supports the risk reduction potential of THS 2.2 for lung diseases in comparison with cigarettes.

Galectin-3 and fibrosis levels in experimental liver injury treated with honey alone or mixed with Nigella sativa seed

Background/aim Galectin-3 (Gal-3) is a multifunctional protein that plays an important role in many biological processes and is linked with fibrogenesis. The aim of this study was to evaluate the effect of honey alone or mixed with Nigella sativa seed (black seed), as hepatoprotective natural remedies on galactin-3 and liver fibrogenesis induced by thioacetamide (TA) in rats. Materials and methods This study was performed on 60 male rats divided into six groups (groups I–VI), with 10 rats each. Group I served as a normal control, groups from II–VI were intoxicated by TA, whereas the groups from III to VI were treated by silymarin, honey, black seed, and honey mixtures, respectively. Levels of liver Gal-3, transforming growth factor β1 (TGF-β1), oxidative stress markers, and serum liver function parameters were determined. Computerized image analysis was used to obtain quantitative measurement of liver fibrotic areas. Results Levels of liver Gal-3, TGF-β1, oxidative stress markers, serum liver transaminases, and fibrotic areas showed significant elevations in TA treated as compared with control. Treatment with silymarin and honey alone or mixed with black seed resulted in lowering liver Gal-3, TGF-β1 levels, and fibrotic areas and improved liver functions and antioxidant status. The mixture doses showed greater effect than honey against TA toxic effects on liver. Conclusion Honey either alone or mixed with black seed reduced Gal-3 level, reduced fibrosis propagation, and ameliorated the toxic effect of TA on liver; moreover, the mixture had greater effect than using honey alone and was closer to silymarin effect.

Effect of Coccinia indica leaf extract on angiotensin converting enzyme (ACE) inhibitor induced hepatotoxicity in wistar albino rats

Summary Enalapril is angiotensin converting enzyme (ACE) inhibitor have been extensively used to treat cardiovascular disorders, including hypertension. Coccinia indica is indigenous plant wildly used in traditional medicinal system including Ayurvedic, Siddha and Unani. The aim of this study was to find out the hepatoprotective activity of C. indica leaf extract against enalapril induced toxic effects. The 24 experimental rats were divided into 4 groups. Group 1 was maintained as control. Group 2 and 3 were treated with single dose of enalapril (1.5g/kg of bwt/orally). After treatment, group 2 maintained as enalapril control. The group 3 was treated with leaf extract of C. indica (400 mg/kg bwt/orally/day) for 7 days. Separate C. indica alone supplementation for 7 days were also maintained. After end of the treatment, animals were sacrificed simultaneously. To determine the serum liver function parameters were estimated. The histophological study of liver tissue was also determined. The changes liver function parameters were observed in enalapril control rats along with histological changes. The C. indica leaf extract supplementation restored all the parameters significantly. In this study, the protective effect of C. indica leaf extract against enalapril induced hepatotoxicity proves, the plant has many medicinal properties.

Lycopene Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Lycopene was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of Lycopene on diethylnitrosamine (DEN)- induced hepatocarcinogensis in rats. Forty-five male albino rats were divided into three groups. Group I (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b. wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN+CCl4 as in group II then treated with lycopene at a dose of (20 mg/kg b.wt/orally) dissolved in tween-80% for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with lycopene to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. Lycopene was able to mitigate liver tissue damage induced by DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level and ameliorate all serum liver function parameters. These findings suggested, the potential efficacy of lycopene as an additional chemo preventive agent in treatment of hepatocellular carcinoma by modulating the apoptosis, anti-inflammatory and detoxification effects.

Spirullina inhibit the development of diethylnitrosoamine induced premalignant phenotype in rat chemical hepatocarcinogensis model

Spirulina was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of spirullina on DEN induced hepatocarcinogensis in rats. Fourty-five male albino rats were divided into three groups. Group Ӏ :(normal control group): rats administered distilled water only. Group II: rats received diethylnitrosoamine (200 mg/kg b.wt/i.p), 2 weeks later rats received (2 ml/kg b.wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN then treated with spirullina platensis at a dose level of (800 mg/kg b.wt/orally) dissolved in distilled water for 6 weeks. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with spirullina platensis to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. Spirullina platensis was able to mitigate liver tissue damage induced by DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level and ameliorate all serum liver function parameters. The obtained results suggest spirullina platensis can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway, improvement of detoxification Enzyme and suppression of inflammation by inhibition of TNF-α overexpression. Spirullina may thus be used as a potentially promising agent to inhibit HCC cell proliferation and may be a novel natural product for the management of HCC.

Astaxanthin-Rich Haematococcus pluvialis Algal Hepatic Modulation in D-Galactose-Induced Aging in Rats: Role of Nrf2.

Purpose: Aging is associated with hepatic morphological and physiological deterioration due to the accumulation of endogenous and exogenous free radicals and the resultant oxidative stress. The present study aims to investigate the effect of Haematococcus pluvialis microalgae on hepatic changes associated with D-galactose (D-Gal)-induced aging in rats.Methods: Aging was induced in rats by daily intraperitoneal injection of D-Gal (200 mg/kg/day) for eight consecutive weeks. D-Gal-injected rats were treated by astaxanthin (ATX)-rich H. pluvialis biomass, its carotenoid and polar fractions for two weeks. Twenty four hours after the last dose, blood samples were collected and the liver tissues were isolated for further biochemical and histopathological examinations.Results: D-Gal induced aging was associated with an elevation in serum liver function parameters, hepatic oxidative stress biomarkers viz., catalase (CAT), glutathione transferase (GST) and myeloperoxidase (MPO), as well as decreased expression of nuclear factor like-2 (Nrf2). Moreover, induction of aging exhibited an elevation of hepatic inflammatory cytokine; interleukin-6 (IL-6) and its modulator; nuclear factor Kappa B (NF-KB). However, treatment of D-Gal injected rats with ATX-rich H. pluvialis restored the serum liver function parameters as well as hepatic CAT, GST and MPO levels with an elevated expression of Nrf2. Treatment with ATX-rich H. pluvialis was also accompanied with a decrease in hepatic levels of NF-KB and IL-6. Histopathological examination emphasized all the previous results. Similarly, all trans-astaxanthin showed high affinity towards Nrf2 with -7.93 kcal/mol estimated free energy of binding as well as moderate affinities towards IL-6 and NF-KB through a docking study.Conclusion: ATX-rich H. pluvialis showed beneficial effects by ameliorating the hepatic changes associated with D-Gal induced aging in rats due to its modulatory role of the Nrf2/Keap pathway.