Levels Of Hepatic Markers Research Articles

Pleurospermum candollei Methanolic Extract Ameliorates CCl4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats.

The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

In vitro analysis of synergistic effect of honey against chemically induced hepatic insult in Balb/c mice.

Human being knows honey since thousands of years for its nutritional and medicinal values. Traditional medicine systems like Ayurveda have elaborated honey as boon for health and patient care. Synergistic effect of honey was research but to a limited extend. Honey is advised with Picrorhiza kurroa for hepatic disorders or hepato-protection in Ayurveda. Here we have examined in vitro synergistic effect of honey when given with Picrorhiza kurroa in acetaminophen-induced hepatotoxicity in Balb/c mice model. We obtained Serum and liver lysate to check levels of hepatic markers, Alkaline phosphatase and Glutathione. The level of alkaline phosphatase raised while glutathione level is reduced during hepatic offence. We observed a compensation of above markers when P. Kurrua, honey and its combination were used in acetaminophen induced hepatic toxicity. We observed a better mice weight gain in combination group (Group IV) compared to control group. This study can pave a way for future research on honey as a better adjuvant for hepatotoxic drugs and other herb-drug interactions researches.

ПРИМЕНЕНИЕ ДОБАВКИ ФИТОДОК® КАРНИТИН ПРИ КОРМОВОМ ТОКСИКОЗЕ ПЕЧЕНИ У СВИНЕЙ

The article considers the effect of the FITODOC® Carnitine feed additive on the clinical characteristics, hematological and biochemical parameters of piglets during the rearing period and fattening pigs with toxic liver dystrophy at a dose of 1 ml and 2 ml per liter of water. There was a reduction in the time of disappearance of clinical manifestations and an increase in body weight; an antianemic effect was noted, which is expressed by an increase in the number of red blood cells and the level of hemoglobin; a decrease in the level of hepatic markers, such as total bilirubin, AlAT, AsAT, and ALP; a decrease in the activity of acute-phase globulins alpha 1 and 2. It is recommended to use the feed additive mainly in groups of growing animals with functional liver disorders at a dose of 1 ml of feed additive per 1 liter of water for 14 days, since at this dosage the maximum effect is achieved in animals of this age group.

Tannic acid administration ameliorates the levels of hepatic markers, carbohydrate metabolizing enzymes and inflammatory markers in the liver of streptozotocin-induced diabetic albino wistar rats

Tannic acid administration ameliorates the levels of hepatic markers, carbohydrate metabolizing enzymes and inflammatory markers in the liver of streptozotocin-induced diabetic albino wistar rats

Antioxidant and hepatopreventive effects of Cassia angustifolia extract against carbon tetrachloride-induced hepatotoxicity in rats

The present study aimed to investigate the preventive effects of methanol fraction from Cassia angustifolia leaf extract (MECA), associated with its phytochemical content, on CCl4-induced hepatic toxicity in adult rats. In the controls, CCl4 induced an increase of serum biochemical parameters and triggered oxidative stress in the liver. MECA caused significant reductions in CCl4-elevated levels of hepatic markers, total cholesterol, triglycerides, and low-density lipoprotein and increased the level of high-density lipoprotein compared to the CCl4 group. Moreover, pretreatment with the MECA produced significant reductions in lipid peroxidation (thiobarbituric acid reactive substances) and protein carbonyl level in liver tissues as compared with the untreated group. The formation of pathological hepatic lesions was strongly prevented by MECA. Overall, this study suggests that administration of MECA has a high potential to quench free radicals and alleviate CCl4-induced hepatotoxicity in rats.

Analysis of quality of grain shortbreads for biological activity and medicalbiological assessment

Quality control of new spelt­based grain crispbreads with the addition of plant additives by the biological activity and medico­biological assessment was examined and analyzed. It was found that plant additives (powders from milk thistle, mountain ash and dog rose fruit) possess a high biological activity. The powders of dog rose and mountain ash are characterized by the high value the activity, which is 2,375 conditional units and 1,250 conditional units, respectively. The value of biological activity of spelt is by 2.55 times higher than that of wheat and is 156 conditional units. The introduction of additives to the composition of crispbreads increases the biological activity of finished products. The grain loaves with the addition of dog rose and ash has the highest biological activity, which is 300 conditional units. and 265 conditional units, respectively. In terms of biological activity, the synergy effect of BAS of original components was detected, while the effect of antagonism was not recorded. A comparative analysis of biological activity of grain crispbreads and crispbreads of well­known brands revealed that the new products are characterized by a high value of biological activity. This attests to the prospects of development and bringing out to consumer market of the new spelt­based products. The results of medical­biological research prove the results of biological activity and indicate that the developed grain crispbreads possess antioxidant activity and hepatoprotective action. This is proved by the indicators of the level of hepatic markers that indicate the hepatoprotective effectiveness of the products. The results of the impact of the additive on dysbiosis degree and on the MDA content revealed that the new products with the addition of milk thistle have antioxidant properties. Based on the research, the expediency of manufacturing new grain spelt­based crispbreads with the addition of enriching additives was substantiated. This enables us to obtain wellness products with a high biological activity and prophylactic properties

Fabrication of a co-culture micro-bioreactor device for efficient hepatic differentiation of human induced pluripotent stem cells (hiPSCs)

Primary hepatocytes, as the gold standard cell type for in vitro models, lose their characteristic morphology and functions after few days. There is an urgent need to develop physiologically relevant models that recapitulate liver microenvironment to obtain mature hepatocyte from stem cells. We designed and fabricated a micro-bioreactor device mimicking the physiological shear stress and cell–cell interaction in liver sinusoid microenvironment. Induced pluripotent stem cells (iPSCs) were co-cultured with human umbilical vein endothelial cells (HUVECs) in the micro-bioreactor device with continuous perfusion of hepatic differentiation medium (100 μL/h). Simulation results showed that flow field inside our perfusion device was uniform and shear stress was adjusted to physiological condition (<2 dyne/cm2). IPSCs-derived hepatocytes (iPSCs-Heps) that were cultured in micro-bioreactor device showed a higher level of hepatic markers compared to those in static condition. Flow cytometry and immunocytochemistry analysis revealed iPSCs cultured in the device sequentially acquired characteristics of definitive endodermal cells (SOX17 positive), hepatoblasts (AFP positive) and mature hepatocyte (ALB positive). Moreover, the albumin and urea secretion were significantly higher in micro-bioreactor device than those cultured in culture dishes during experiment. Thus, based on our results, we propose our micro-bioreactor as a beneficial device to generate mature hepatocytes for drug screening and basic research.

Effects of Berberine chloride on the liver of streptozotocin-induced diabetes in albino Wistar rats

The goal of the present study is to evaluate the effect of Berberine chloride (BC) on the liver of streptozotocin (STZ) induced diabetic rat. Diabetic rats were treated with BC (50 mg/kg b.w) or glibenclamide (6 mg/kg b.w), daily for 45 days. After BC treatment in diabetic rats, there was a significant (P < 0.05) decline in the levels of hepatic markers, lipid peroxidation markers such as lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS), and pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor kappa-B-p65 (phospho-NF-κB p65), cyclooxygenase (COX-2), nitric oxide synthase (iNOS) as well as pro-apoptotic mediators such as Bax and cytochrome c. A significant (P < 0.05) increase in hexokinase, glucose-6-phosphate dehydrogenase, enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and non-enzymatic antioxidants such as glutathione (GSH), vitamin E and vitamin C, as well as anti-apoptotic protein Bcl-2 were observed in the liver of BC treated diabetic rats. Thus, from these findings, it can be concluded that the administration of BC notably recovered the liver from hyperglycemia induced antioxidant imbalance, inflammation and apoptosis as well as rectified the imbalance in carbohydrate metabolizing enzymes.

BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES OF TRADITIONAL SIDDHA FORMULATION ON CCL4 INDUCED LIVER FIBROSIS IN RATS

ABSTRACTObjective:The main objective of this study is to evaluate therapeutic activity of traditional siddha formulation on CCl4 induced liver fibrosis in rats.Methods:Plant materials collected, shade dried, mixed equal proportion. This mixture was used for extract or kasayam preparation. Twenty four male Wistar albino rats were randomly divided into four groups of six rats each. The normal control group was allowed free access to food and water. Drug control group was allowed to daily intragastric administration of traditional siddha formulation 400mg per kg b.wt per day. Liver damage was performed in the remaining two groups with an i.p.injection of a 1.0 mL/kg b.wt CCl4 and olive oil (2:3 v/v) mixture, twice weekly for 8 weeks. All rats, with the exception of the injury model group, were intragastrically administered traditional siddha formulation (TSF) dosage 400 mg/ kg b.wt /day from 5th week to end of experiment of CCl4 intoxicated rats. The serum levels of hepatic markers and hydroxyproline (Hyp) in the rat livers were measured. Histopathological changes in the liver were assessed for each group using H&amp;E staining and Masson Trichrome examination.Results:Traditional siddha formulation significantly reverse the liver function in CCl4 intoxicated rats correlate with both biochemical and histopathological changesConclusion:Traditional siddha formulation a promising drug for treating liver fibrosis.Keywords: Traditional siddha formulation, Liver fibrosis, CCl4 and Vaithiyars

Hepatoprotective Effects of Zataria Multiflora Ethanolic Extract on Liver Toxicity Induced by Cyclophosphamide in Mice

Although cyclophosphamide (CP), an alkylating agent, has been extensively used in chemotherapy, it possesses a wide spectrum of adverse effects including hepatotoxicity. This study was aimed to evaluate the protective effects of Zataria multiflora against hepatic damage induced by CP in mice.Mice were orally (gavages) pretreated with the ethanolic extract aerial parts of Zataria at doses of 50, 100, 200, or 400 mg/kg for 7 consecutive days before a single intraperitoneal injection of 200 mg/kg CP. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination.Serum levels of hepatic markers were significantly increased after only CP treated animals but restored in Zataria pretreated groups. A single dose of CP administration also markedly induced abnormality in the levels of several biomarkers associated with oxidative stress in liver tissues homogenates. However, pretreatment with Zataria significantly inhibited the abnormality of antioxidant enzymes defense system in the liver tissues. In addition, histopathological studies proved that CP causes damage to the liver, and this was evidenced by the induced dilated and congested sinusoidal space, lymphocytic infiltration between hepatocytes, portal space with moderate to severe inflammation and necrotic hepatocyte with absence of nuclei. Zataria effectively protected animals against CP-induced hepatic tissue damages.Our results reveal that Zataria produces a potent hepatoprotective role and could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.

Effect of Piper betle on Hepatotoxicity and Antioxidant Defense in Ethanol-Treated Rats

ABSTRACT Piper betle L. leaves are commonly used masticatory material in Asia. Because hepatotoxicity of ethanol may result from oxidative damage, we investigated the effect of P. betle leaves on key hepatic markers and antioxidant defense against ethanol toxicity to evaluate the hepatoprotective activity of P. betle. Administration of ethanol (7.9 g/kg body wt.) for 60 days resulted in significant elevation of key hepatic markers such as alkaline phosphatase, γ-glutamyl transferase and bilirubin in serum and disturbances in antioxidant defense when compared to normal. Coadministration of aqueous extract of P. betle leaves for 30 days (100, 200, and 300 mg/kg body wt.) significantly decreased the level of hepatic markers and lipid peroxidation markers such as thiobarbituric acid reactive substances and hydroperoxides. The extract also improved the antioxidant status by increasing the levels of nonenzymatic antioxidants such as reduced glutathione, vitamin C, and vitamin E. The leaf extract at 300 mg/kg body weight was more effective than other doses. The results were comparable with the known hepatoprotective drug, silymarin. These results suggest that P. betle exhibits hepatoprotective and antioxidant effects in ethanol-treated rats.

CISPLATIN (CDDP)-INDUCED ACUTE TOXICITY IN AN EXPERIMENTAL MODEL OF HEPATIC FIBROSIS

Cisplatin (CDDP)-induced acute toxicity was investigated in an experimental model of liver fibrosis produced through repeated intraperitoneal injections of swine serum in rats. A significant increase in level of hepatic markers, such as plasma ASAT, LDH, glucose, total cholesterol and bile acid levels, and a significant decrease in the plasma triacylglycerol level were observed. Slight histological changes, such as necrosis, vacuolar degeneration, and the proliferation of bile ducts were observed as compared with the control fibrotic rats. On the other hand, a significant increase in levels of renal markers, such as plasma BUN and creatinine levels as well as more remarkable tubular degeneration were observed. From these results, CDDP's hepatotoxicity was slight while its nephrotoxicity was more extensive in fibrotic rats.

An open clinical trial of naltrexone for amphetamine dependence: Compliance and tolerability

The aim of the study was to assess the feasibility of naltrexone as a potential pharmacotherapy for amphetamine dependence. The study design was an open-label clinical trial with 20 amphetamine-dependent patients receiving 12 weeks of treatment comprised of naltrexone (50 mg) along with relapse prevention therapy. Patients were assessed weekly for adverse events and compliance to medication. Tolerability to naltrexone was measured by patient's self-report and observed adverse effects along with plasma markers of hepatotoxicity. Compliance to treatment was measured by number of treatment days attended and by the presence of naltrexone's metabolite, 6-β-naltrexol in urine. Majority of the patients tolerated the medication well, also during relapse. Mild headache, nausea and abdominal pain were reported (n=3) but subsided within 2 weeks. Plasma levels of hepatic markers did not reveal any significant increase from baseline. Eleven out of 20 patients complied with the treatment and there was a significantly higher proportion of positive tests of 6-β-naltrexol in urine among patients completing 12 weeks of treatment compared to those who did not (77% vs. 22%). The frequency and amount of amphetamine consumed was significantly lower during treatment compared with pre-treatment consumption (P<0.01). In conclusion, naltrexone was well tolerated with moderate rates of compliance, supporting the feasibility of investigating this compound in a larger placebo-controlled trial as a potential pharmacotherapy for amphetamine dependence.