Histological Examination Of Liver Research Articles

TOXICO-PATHOLOGICAL ASSESSEMENT OF Nerium oleander ROOTS AND LEAVES ON WISTAR RAT

The aim of the study was to evaluate the toxic effects of Nerium oleander roots (R) and leaves (L) aqueous extract on Wistar rat. Serum chemistry, epididymal sperm parameters and histological examination of liver, kidney and brain were assessed after twelve consecutive day’s oral administration of N. oleander. The extracts of R1, R2, L1 and L2 induced no treatment-related adverse effects with regard to general behaviors, hematological, serum chemistry, epididymal sperm parameters and histological profiles of liver, kidney and brain. However, the higher doses (R3, L3) led to, diarrhea, weakness, anorexia, frequent urination, and nasal hemorrhage, with no mortality. The hematological data revealed a significant increase in the levels of hematocrit and platelets in both L3 and R3 compared to the control. However, these two extracts have not affected the level of RBC, hemoglobin, WBC, and lymphocytes, while the L3 has reduced the concentration of glucose and increased that of urea. However, triglycerides, total cholesterol, alanine aminotransferease, albumin, conjugated bilirubin, potassium and calcium levels of L3 and R3 were not statistically significant compared to the control. Simultaneously bilirubin concentration was increased significantly in L3 and R3. There were no significant differences in epididymal sperm analysis when compared to the control. Adverse histological changes were observed in both liver and kidney as well as in the brain. To conclude, N. oleander extracts have disturbed the levels of certain vital variables in rats at higher dose, in which caution should be taken during the use of this plant.

Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent.

The present study is based on screening new and potent synthetic heterocyclic compounds as anti-diabetic drugs using various computational tools, lab experiments, and animal models. A potent synthetic compound 2-(3-benzoyl-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-1-(2-bromophenyl) acetamide (FA2) was checked against diabetes and screened via enzyme inhibition assays, enzyme kinetics against alpha-glucosidase and alpha-amylase. Protein-ligand interaction was analyzed via molecular docking and toxicological analysis via ADMET. Experimental animals were used to examine the compound FA2 safety, delivery, and check various biochemical tests related to diabetes like fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin level. Histography of liver, kidney, and pancreas was also performed. Results showed that FA2 had binding energy of -7.02 Kcal/mol and -6.6 kcal/mol against α-glucosidase (PDB ID: 2ZE0) and α-amylase (PDB ID: 1B2Y), respectively. Moreover, in vitro enzyme inhibition assays and enzyme kinetics against α-glucosidase and α-amylase were performed, and FA2 showed IC50 at 5.17 ± 0.28 µM and 18.82 ± 0.89 µM concentrations against α-glucosidase and α-amylase, respectively. Kinetics studies showed that the FA2 compound impeded α-glucosidase and α-amylase as a non-competitive mode of inhibition with Ki' values -0.320 ± 0.001 and 0.141 ± 0.01, respectively. FA2 was further analyzed on alloxan-induced mice for 21 days. Biochemical tests (fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin levels) and histological examination of liver and kidney showed that the FA2 compound showed better results than acarbose. Histology of pancreas found to show the maintenance of normal pancreatic acini and Langerhans islets in FA2 treated mice compared to acarbose and nontreated diabetic controls. Investigating anti-diabetic potential of FA2 compound showed that the selected benzothiazine derivative has tremendous importance in reducing dose concentration and side effects.

A Meta-Analysis of How Nonalcoholic Fatty Liver Disease Affect Antiviral Treatment of Patients with e Antigen-Positive Chronic Hepatitis B.

Background Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are both the most common underlying diseases leading to cirrhosis and hepatocellular carcinoma, and NAFLD and HBV infection are the first and second leading causes of chronic liver disease in China. However, there are still a lot of controversies about whether the combined presence of CHB and NAFLD will affect the course or outcome of liver disease together with HBV, and how the two affect each other. Objective To investigate the effect of nonalcoholic fatty liver disease (NAFLD) on antiviral therapy in patients with chronic hepatitis B (CHB). Methods Computer searches of databases such as PubMed, CNKI, VIP.com, and Wanfang Data Knowledge Service Platform were used. The time frame was from the creation of the database to June 2022. The search subject terms were hepatitis B, CHB, or NAFLD. The observation group consisted of patients with e antigen-positive CHB with NAFLD, and the control group consisted of patients with e-antigen + CHB. Extracts including title, name, date of publication, number of samples, antiviral drugs, and outcome indicators were used for Meta-analysis. Funnel plots were drawn to analyze literature bias. Results Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results. Meta-analysis showed that CHB patients with NAFLD had lower efficacy than CHB patients after 48 weeks of antiviral treatment with nucleotide analogs, as measured by three outcome indicators HBV DNA conversion rate, ALT-normalization, and HBeAg conversion rate. Conclusion NAFLD reduces the effect of antiviral therapy in CHB patients, and the clinicopathological features of patients with NAFLD combined with chronic hepatitis B are different from those of patients with chronic hepatitis B alone, so early diagnosis by liver histological examination should be actively performed and reasonable antiviral therapy should be administered.

A high-fat, high-fructose diet induced hepatic steatosis, renal lesions, dyslipidemia, and hyperuricemia in non-obese rats

Excessive consumption of fat and sugar is associated with various chronic diseases. However, the variation of fat and sugar content in the diet greatly affected the outcome. In this study, a high-fat, high-fructose diet (HFHFD) formula was made with a composition of 31.99% carbohydrate, 40.7% fat, 11.8% protein, and an additional 30% fructose drink to confirm the effects of HFHFD on metabolic health and pathological changes in organs, especially the liver, kidneys, pancreas, muscles, and spleen. A total of 24 male Wistar rats aged 8–12 weeks were divided into four groups: standard chow (SC), HFHFD, SC + carbon tetrachloride (CCl4), and HFHFD + CCl4. After eight weeks of dietary intervention, body mass index, obesity index, lipid profiles, liver function tests, fasting blood glucose, serum uric acid and urea levels, and tissue histopathology were examined. HFHFD with the main unsaturated fatty acids of linoleic acid (14.57%) and palmitoleic acid (8.28%), the main saturated fatty acids of stearic acid (13.62%) and myristic acid (10.09%), and a low trans-fatty acids content, did not promote the rats to become obese. However, liver histology examination showed severe hepatic steatosis (78.33%), leading to steatohepatitis accompanied by an increase in serum ALP (p < 0.01), triglyceride (p < 0.001), total cholesterol (p < 0.05), and uric acid (p < 0.001) levels. Other histological features showed moderate lesions (45%) of the kidney, slight vacuolization of the pancreas, and a mild increase of inflammatory cells in the spleen and muscle. So, this study found that although HFHFD did not promote obesity within 8 weeks of administration, it induced hepatic and renal lesions, dyslipidemia, and hyperuricemia as a metabolic consequence of excessive fatty acids and fructose.

Effects of Fatty-Type and Lean-Type on Growth Performance and Lipid Droplet Metabolism in Pekin Ducks.

The reasons for differences in lipid depositions between fatty-type (F-T) and lean-type (L-T) ducks remain unknown. The present study aimed to compare the growth performance, lipid deposition, and gene expression related to lipid droplet formation in F-T and L-T Pekin ducks. One-day-old, 140 each L-T and F-T male ducks were selected and distributed separately into 20 replicate cages. All ducks were fed commercial diets up to 35 d of age. F-T ducks had a higher average daily gain from 21 to 28 d of age. On 35-day-old, F-T ducks had higher serum levels of high- and low-density lipoprotein cholesterol, cholesterol, albumin, and hydroxybutyrate dehydrogenase activity than L-T ducks. F-T ducks had higher abdominal fat and subcutaneous fat percentages than those in L-T ducks. Liver histological examination showed that L-T ducks contained more lipid droplets in the liver, which gradually decreased with increasing age. The average adipocyte area and diameter of abdominal fat and subcutaneous fat in the F-T and L-T ducks increased with age and were higher in F-T ducks than those in L-T ducks. Furthermore, the gene expression of perilipin 1, perilipin 2, angiopoietin-like protein 4, adipose triglyceride lipase, alpha/beta-hydrolase domain-containing protein 5 (ABHD5), and serine/threonine kinase 17a in the liver, abdominal fat, and subcutaneous fat of F-T ducks was higher than that in L-T ducks, and it increased with age. Compared to L-T ducks, F-T ducks had higher expression of ABHD5 in the abdominal fat and subcutaneous fat and lower expression in the liver. Thus, F-T ducks displayed lower hepatic lipid deposition and a higher percentage of abdominal fat and subcutaneous fat, suggesting that F-T ducks had higher lipid storage capacity due to increased gene expression related to lipid droplets.

HPLC Analysis and the Antioxidant and Preventive Actions of Opuntia stricta Juice Extract against Hepato-Nephrotoxicity and Testicular Injury Induced by Cadmium Exposure.

Opuntia stricta is a rich source of phenolic compounds. This species generally has strong antioxidant activities in vitro and in vivo. This study aimed to analyze the antioxidant properties of phenolic compounds isolated from Opuntia stricta, including its radical scavenging activities and preventive action against Cd-induced oxidative stress in rats. To assess the protection of prickly pear juice extract (PPJE) against Cd-induced hepato-nephrotoxicity and testicular damage, male albino rats received PPJE (250 mg kg−1) and/or Cd (1 mg kg−1) by oral administration and injection, respectively, for five consecutive weeks. The preventive action of PPJE was estimated using biochemical markers of kidney and liver tissues, antioxidant status, and histological examinations. In the present study, the lipid peroxidation, protein carbonyls, antioxidant status, and metallothionein levels were determined in different tissues. The chromatographic analysis indicated that PPJE extract is very rich in phenolic compounds such as verbascoside, catechin hydrate, and oleuropein. Our results showed that PPJE-treated rats had significantly (p < 0.05) decreased Cd levels in liver and kidney tissues. In addition, the administration of PPJE induced a significant (p < 0.05) decrease in lipid peroxidation of 30.5, 54.54, and 40.8 in the liver, kidney, and testicle, respectively, and an increase in antioxidant status in these tissues. Additionally, PPJE showed a strong ability to protect renal, hepatic, and testicular architectures against Cd exposure. This study revealed that PPJE protects against the toxic effects of Cd, possibly through its free radical scavenging and antioxidant activities.

Evaluation of Acute and Subacute Toxicity and LC-MS/MS Compositional Alkaloid Determination of the Hydroethanolic Extract of Dysphania ambrosioides (L.) Mosyakin and Clemants Flowers.

Dysphania ambrosioides (L.) Mosyakin and Clemants is a medicinal plant that has traditionally been used to cure a range of diseases. There has been no thorough investigation of the potential toxicity of this plant. The objective of this study is to assess the acute and subacute toxicity of D. ambrosioides hydroethanolic extract (DAHE), as well as it alkaloids composition, utilizing LC-MS/MS analysis. An in silico approach was applied to determine pharmacokinetic parameters and to predict the toxicity of D. ambrosioides identified alkaloids. A 14-day treatment with a single oral dose of 1–7 g/kg was carried out to investigate acute toxicity. DAHE was given orally at dosages of 5, 50, and 500 mg/kg for 15 days in the subacute toxicity investigation, and body weight and biochemical parameters were evaluated. Livers, kidneys, lungs, and heart were examined histologically. Chromatographic investigation revealed the existence of nine alkaloids, with N-formylnorgalanthamine being the most prevalent. The oral LD50 value of DAHE was found to be 5000 mg/kg in an acute toxicity study. No variations were observed with respect to food intake, water consumption, mortality, or body and organ weight in the subacute toxicity study. On the other hand, DAHE (500 mg/kg) significantly enhanced alanineaminotransferase, aspartate aminotransferase, and urea. Liver and kidney histological examinations revealed modest infiltration of hepatocyte trabeculae by inflammatory cells in the liver and slight alteration in the kidney histoarchitecture. According to our findings, DAHE exhibits low to moderate toxicity.

On the Compatibility of Fish Meal Replacements in Aquafeeds for Rainbow Trout. A Combined Metabolomic, Proteomic and Histological Study.

The sustainable development of modern aquaculture must rely on a significant reduction of the fish meal (FM) used in aquafeed formulations. However, FM substitution with alternative ingredients in diets for carnivorous fish species often showed reduced nutrient absorption, significantly perturbed metabolisms, and histological changes at both hepatic and intestinal levels. In the present study, rainbow trout (Oncorhynchus mykiss) were fed three different experimental aquafeeds. A control diet with higher FM content (27.3%) than two test formulations in which FM was substituted with two more sustainable and promising alternatives: insect meal (Hermetia illucens larvae = 10.1%, FM = 11.6%) and poultry by-products meal (PBM = 14.8%; FM = 11.7%). Combined metabolomics and proteomics analyses of fish liver, together with histological examination of liver and intestine demonstrated that a well-balanced formulation of nutrients in the three diets allowed high metabolic compatibility of either substitution, paving the way for a deeper understanding of the impact of novel raw materials for the fish feed industry. Results show that the main metabolic pathways of nutrient absorption and catabolism were essentially unaltered by alternative feed ingredients, and also histological alterations were negligible. It is demonstrated that the substitution of FM with sustainable alternatives does not have a negative impact on fish metabolism, as long as the nutritional requirements of rainbow trout are fulfilled.

Antidiabetic Properties and Toxicological Assessment of Antidesma celebicum Miq: Ethanolic Leaves Extract in Sprague-Dawley Rats.

Antidesma is a genus of plants, and its several species are known to have antidiabetic properties. Leaves of Kayu Tuah (Antidesma celebicum Miq) have been proven to have the best α-glucosidase inhibition ability compared to other species in the Antidesma genus, as evidenced by the in vitro α-glucosidase inhibition test. However, no scientific studies have reported its antidiabetic properties and toxicity in vivo. Therefore, this research managed to verify the antidiabetic features and safety of ethanolic extract of A. celebicum leaves (EEAC) in Sprague–Dawley rats. Male rats (170–280 g) were induced diabetic with streptozotocin (35 mg/kg BW) and fed a high-fat diet comprising 24% fat, whereas control group rats were given a standard diet. Rats were treated with EEAC at 200 and 400 mg/kg BW doses for 28-days and 60 mg/kg BW acarbose for the control group. Determination of antidiabetic properties was done by analyzing lipid profiles as well as fasting blood glucose. After confirming the antidiabetic properties of EEAC, the toxicological assessment was determined using the fixed-dose method. General behavior changes, appearance, signs of toxicity, mortality, and body weight of animals were marked down during the observation period. When the treatment period ended, hematological, biochemical, and histological examinations of liver, kidneys, and heart sections were performed. The results confirmed that EEAC reduced fasting blood glucose levels and stepped forward lipid profiles of rats. Also, all animals survived, and no obvious destructive outcomes were noticeable during the study. As EEAC has promising results toward hyperglycemia and hyperlipidemia and has been proven safe through toxicity tests, it can be concluded that EEAC has good potential to be further developed into antidiabetic drugs.

Hepatotoxicity of the Major Anthraquinones Derived From Polygoni Multiflori Radix Based on Bile Acid Homeostasis

Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.

The role of CGPR ‐ receptor antagonist in the plastic process on the hepatopathies with toxical genesis

Many research results showed that the CGPR concentration in the blood plasma has significantly increased by hepatopathies with different genesis. The hyperkinetic portal blood flow has caused this. This research's primary hypothesis was the potentiation of CGPR ‐ receptor antagonist to the liver's plastic process by toxical hepatopathies provocation. The study aimed to evaluate the influence of combination the hepatoprotective agent “Hepaton‐vet” (dose ‐0.5 mg/kg per rat during 7th days) and monoclonal antibodies G2 (IgG2, dose ‐0.75 ml/kg per rat one‐time before experimental start) on the hepatopathy's regenerative process which was 1,2‐dichloroethane induced during 7th days with following orthothanasia (the method by Malcom A., Steele M.D., 1991). White outbred rats were used (n=20). The body mass of rats was ranged from 180 to 220g. The liver histological examinations were performed by a visual method using Image J Software. Thus, the histologic pattern of rats' liver was included in the connective tissue membrane, which was obduced the liver externally. The hepatic lobules of rats have had shapes of hexagon prism without clean‐cut peripheries. The interlobular tissue in the lobule's feather included the interlobular vena, the interlobular artery, and the bile duct lined with cuboidal epithelium. The lobular base was sited central vein with hepatic plates, which were formed hepatocytes. The rats' hepatocytes had a wrong multiangular shape were was 60 % of all in the liver cells pattern was typical for liver with high regenerative level without signs of vassal‐ mesenchymal reactions, which was correlated with CGPR ‐ receptor antagonist. So, we can assume that the CGPR ‐ receptor antagonist drugs have a great variety in their administration, including the potentiation of other drugs used in the pharmacorrection of different pathologies. The balanced influence on the CGPR – receptors significantly influence the homeostasis maintenance and the nociception of the hepatobiliary system.

Prospects of transient elastography’ using in the veterinary hepatology

Elastography is the qualitative and quantitative analysis of tissue’ elastic characteristics. The diagnostic of hepatopathies is based on the puncture biopsy of the liver. At the same point, the low biochemical activity of liver diseases is not always associated with the analogic histologic pattern. There were not excluded the advance of hepatic pathology. The primary hypothesis of this research was the prospects of transient elastography used in the diagnosis of hepatic disorder in animals. The methodology is about the formation of rotational waves in the determinate organ and measuring their velocity. The rotational wave has generated by a special detector which has the source of mechanical vibrations. The detector is located on the patient’s body surface in the zona of the organ’s projection. The studies were carried out in the laboratory animals, which were rabbits (n=20). The tool was used iLIvTouch. Standard methods also performed the liver biopsy and histological examination. Thus, we have detected the correlation between parameters of liver stiffness and the biopsy’ results performing transient elastography. The histology was pointing to the specific diagnosis: the fatty hepatosis with liver stiffness in 3.8‐4.2 kPa (n=10, the normal range was 5.8 kPa). Liver fibrosis was also diagnosed with liver stiffness in 6.2‐6.8 kPa (n=5) and toxic hepatitis with liver stiffness in 3.2‐3.6 kPa (n=5). The results of our research on laboratory animals after hepatopathies’ induction with different pathogenesis showed that the parameters of liver stiffness using transient elastography correlated with the results of the morphological evaluation. So, we can assume prospects of transient elastography using equally with standard methods.

Hydrochloride Berberine ameliorates alcohol-induced liver injury by regulating inflammation and lipid metabolism

AimsBerberine hydrochloride (BBR) is efficacious in relieving alcoholic liver injury (ALI) in animal models, but its underlying mechanisms remains largely unclear. Methods and resultsIn the study, the rats were divided into control group, model group, model with BBR group, and control with BBR group, and given corresponding treatment for 4 weeks. RNA-Seq, ELISA and RT-PCR were performed to explore the potential mechanisms of BBR in ALI. Treatment of rats with BBR (200 mg/kg/d, gavage, once daily) over 4 weeks diminished 4 g/kg/d alcohol-induced inflammation and lipid deposition. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in BBR-treated rats. Hepatic gene expression profile detected that BBR suppressed ethanol-stimulated overexpression of thyroid hormone responsive gene-THRSP. And overexpression of THRSP-responsive genes (fatty acid synthase-FASN, adenosine monophosphate activated protein kinase α-AMPK-α, acetyl-CoA carboxylase-ACC, ATP-citrate lyase-ACLY) responsible for fatty acid synthesis was also downregulated by BBR. Additionally, BBR downregulated expression of cluster of differentiation 36-CD36 and upregulated expression of peroxisome proliferator-activated receptor α (PPARα) and its target genes (carnitine palmitoyltransferase 1 α-CPT1α and acyl-CoA oxidase 1-ACOX1). Meanwhile, BBR treatment suppressed systemic inflammation by mediating a reduction in IL-10, TNF-α, LPS, and ET, but elevated IL-6. ConclusionsThe results indicated that BBR alleviated alcoholism-induced hepatic injury by suppressing inflammation (IL-10, TNF-α, LPS, ET and IL-6), and regulating fatty acids uptake (CD36), lipid synthesis (THRSP, FASN, AMPK-α, ACC, ACLY) and lipid oxidation (PPARα, CPT1α, ACOX1), and THRSP may be its novel target.

Influence of hydroethanolic extract of Cassia spectabilis leaves on diclofenac-induced oxidative stress and hepatorenal damage in Wistar rats

BackgroundThe medicinal potential of plant extracts for the management of liver and kidney disorders in humans has been harnessed for the past several centuries. However, the abundant plant resources have not been fully investigated, thus this study was initiated to evaluate the influence of Cassia spectabilis leaves extract (CSE) on diclofenac-induced oxidative stress and hepatorenal damage in Wistar rats. The rats in the 1st group were injected with normal saline, and rats in the 2nd group were injected with diclofenac sodium (DF) by intramuscular route. Rats in the 3rd to 5th groups were treated with graded doses of CSE by oral gavages, and injected with DF. The serum markers of oxidative stress and hepatorenal damage in rats were estimated by biochemical assays. In addition, histological examinations of liver and kidney tissues were evaluated.ResultsThere was significant (p < 0.05) increase in the levels of total bilirubin, ALT, AST, ALP, GGT, LDH, urea, creatinine, uric acid, potassium ions, and MDA of rats injected with DF when compared with normal control. The treatment of DF-injected rats with CSE significantly (p < 0.05) reduced the levels of these markers of hepatorenal damage in rats when compared with DF control. There was significant (p < 0.05) decrease in the levels of GSH, SOD, CAT, GPx, GST, sodium ions, proteins and G6Pase after injection of rats with DF when compared with normal control. However, treatment of DF-injected rats with CSE significantly (p < 0.05) increased the levels of these markers of antioxidant status and oxidative damage in hepatorenal tissues of rats when compared with DF control. The photomicrographs of hepatorenal tissues showed structural features which corroborated our biochemical findings in this study.ConclusionThe findings of this study have shown that CSE may have protective effect against DF-induced oxidative stress and hepatorenal damage in Wistar rats. Thus, the medicinal potential of this plant leaves extract may be harnessed for the development of phytotherapeutic products.

Evaluation of Hepatoprotective Potential of Polyherbal Preparations in CCl4-Induced Hepatotoxicity in Mice.

Background Polyherbal formulations (PLFs) have been widely used for liver protection, treatment for hepatic dysfunction, and regeneration. They can also enhance appetite and protect the gastrointestinal tract from injury. In spite of the prevalent use, there is a need of scientific evidence on their effectiveness and safety. The objective of the present study was to assess the hepatoprotective effect of polyherbal formulations (commercially available in Bangladesh namely Heptaliv, Holyliv, Icturn, and J-deenar) in CCl4-induced hepatotoxicity in mice. Methods In this study, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, per os.) followed by single subcutaneous injection of CCl4 (1 ml/kg body weight, diluted with olive oil in 1 : 1 ratio) on day 8. Twenty-four hours after CCl4 administration, the mice were monitored for the effects of PLFs on liver morphology, biochemical parameters including serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin. Phenobarbitone-induced sleeping time and histopathology changes in liver tissues were also monitored. Results CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in AST, ALT, ALP, and total bilirubin. Phenobarbitone-induced sleeping time and infiltration of inflammatory cells and centrizonal necrosis on histological examination of liver demonstrated hepatic injury after CCl4 administration. However, the administration of Icturn and J-deenar polyherbal formulations at the higher dose significantly decreased the levels of AST, ALT, ALP, and total bilirubin. Moreover, pentobarbitone-induced sleeping time and histopathological analysis also revealed significant improvement as result of treatment with formulations Icturn and J-deenar. Conclusion Our results confirmed that polyherbal formulations (Icturn and J-deenar) can significantly prevent CCl4-induced hepatotoxicity in mice, demonstrating their protective effect for liver.

Evaluation of Protective Action of Selenium Against Hepatotoxicity Caused by Methotrexate In Mice

Drug induced liver injury has been regarded as the main cause of acute liver injury in many countries. Objectives: To evaluate the protective action of selenium against hepatotoxicity caused by methotrexate in mice. Study Design: Randomized, single blinded study. Methodology: Present study was done on 18 mice (n = 18) after taking approval from Ethical Review Committee. Administration of methotrexate induced hepatotoxicity. Selenium was administered along with methotrexate in order to evaluate the protective effects. The extent of hepatotoxicity and protective effects were analyzed by measuring levels of serum liver enzymes and histological examination of liver samples. Statistical analysis: One way ANOVA test was applied for comparison of biochemical markers between groups. Chi Square test was also applied for histopathological results. Results: In present study, results showed that significant hepatotoxicity was observed (p &lt; 0.05) with elevated levels of serum liver enzymes with methotrexate. Selenium was found to significantly reduce the hepatotoxicity (p &lt; 0.05). Histological examination revealed steatosis, which was found to be markedly decreased after treatment with selenium along with methotrexate. Conclusion: We concluded that selenium helped to protect against hepatotoxicity induced by methotrexate in mice. Keywords: Drug induced liver injury, Hepatotoxicity, Methotrexate and Selenium.

Intestinal microbiomics and liver metabolomics insights into the preventive effects of chromium (III)-enriched yeast on hyperlipidemia and hyperglycemia induced by high-fat and high-fructose diet

In recent years, organic chromium (III) supplements have received increasing attentions for their low toxicity, high bioavailability and wide range of health-promoting benefits. This study aimed to investigate the preventive effects of chromium (III)-enriched yeast (YCr) on high-fat and high-fructose diet (HFHFD)-induced hyperlipidemia and hyperglycemia in mice, and further clarify its mechanism of action from the perspective of intestinal microbiomics and liver metabolomics. The results indicated that oral administration of YCr remarkably inhibited the aberrant elevations of body weight, blood glucose and lipid levels, hepatic cholesterol (TC) and triglyceride (TG) levels caused by HFHFD. Liver histological examination showed that oral YCr intervention inhibited HFHFD induced liver lipid accumulation. Besides, 16S rDNA amplicon sequencing showed that YCr intervention was beneficial to ameliorating intestinal microbiota dysbiosis by altering the proportion of some intestinal microbial phylotypes. Correlation-based network analysis indicated that the key intestinal microbial phylotypes intervened by YCr were closely related to some biochemical parameters associated with glucose and lipid metabolism. Liver metabolomics analysis revealed that dietary YCr intervention significantly regulated the levels of some biomarkers involved in purine metabolism, glycerophospholipid metabolism, citrate cycle, pyrimidine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and so on. Moreover, dietary YCr intervention regulated the mRNA levels of key genes associated with glucose, cholesterol, fatty acids and bile acids metabolism in liver. These findings suggest that dietary YCr intervention has beneficial effects on glucose and lipid metabolism by regulating intestinal microbiota and liver metabolic pathway, and thus can be served as a functional component to prevent hyperlipidemia and hyperglycemia.

Histomorphometric features of hepatic toxicity caused by carbamazepine and its amelioration with vitamin E.

Background: Carbamazepine, a commonly prescribed anti-epileptic drug, is potentially hepatotoxic. This laboratory-based experimental study was designed to observe the toxicity of Carbamazepine and the ameliorative effects of Vitamin E on liver tissue.&#x0D; Methodology: A total of 54 rats were randomly divided into 3 groups. Group A was the control; group B was given oral Carbamazepine, and group C was given Carbamazepine with Vitamin E daily for 6 weeks. At the end of the study period, animals were sacrificed, their liver was preserved, and tissue was stained with Hematoxylin and Eosin.&#x0D; Results: The mean final body weights of Carbamazepine treated group B (147.27 ± 13.72 gm) and Carbamazepine + Vitamin E protected group C (164.43 ± 10.73 gm) were decreased significantly in comparison to control A (194.03 ± 14.87 gm). Mean absolute and relative liver weights were increased significantly in groups B &amp; C as compared to group A. Histological examination of liver in group B showed disturbed architecture of hepatic lobules including congested central vein, dilated sinusoids, pyknotic nuclei, steatosis, portal vein dilatation, hemorrhages, and mononuclear infiltration in the portal triad and around the central vein. These changes were reduced in group C. Micrometry confirmed the histological findings, with a significant decrease in mean hepatic cell count and mean hepatocyte nuclear diameter of group B as compared to control group A (6.00 ± 1.41 &amp; 5.62 ± 0.69 µm respectively), and a significant increase in mean hepatocyte diameter of group B in comparison to group A (17.44 ± 1.29 µm).&#x0D; Conclusion: This study showed that Carbamazepine caused hepatotoxicity while Vitamin E was helpful in its amelioration.

Naja nubiae venom ameliorate hepatorenal toxicity induced by Gentamicin in rats

Background: In developing countries, there is no doubt that acute kidney injury and chronic liver diseases have a major impact on health. Different venom components are gaining renewed interest as potential sources of new pharmacological compounds relevant for human therapeutics. Aim: The present study was designed to evaluate the therapeutic efficacy of the crude venom extract of the Egyptian spitting cobra (Naja nubiae) venom extract against gentamycin–induced nephrotoxicity and hepatotoxicity in rats. Methods: Eighteen male Wistar rats were divided into three groups, control, gentamycin, and venom extract. The hepatorenal toxicity model was induced by gentamycin (80 mg/kg, intraperitoneal) for 8 days. Results: LD50 of venom extract in rats was 0.2mg/kg. The venom extract group showed a significant decrease in the liver enzymes, urea, uric acid, creatinine, malondialdehyde meanwhile glutathione reduced and catalase levels increased. Histological examination of liver and kidney mild protective efficacy with less extensive degenerative changes in the tissues of venom extract grou Conclusion: The results of the present investigation showed that administration of venom extract proved therapeutic efficacy against gentamycin -induced hepatorenal dysfunction by maintain the normal functional status of the liver and kidney and normalized the antioxidant system.

Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients.

Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. A total of 46 CHB patients received liver biopsies (BSV, n=29; TDF, n=17). After 48weeks of treatment, virological response rate was comparable between the groups (P=0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P=0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48weeks of BSV or TDF treatment (P<0.001) without intergroup differences (P=0.349). The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.