Liver Function Enzyme Activities Research Articles

Threonine supplementation stimulates immune, antioxidant and liver functions of largemouth bass, Micropterus salmoides

Threonine is an essential amino acid required in the diets for regular growth of fishes, but information is inadequate regarding the effects of threonine on immunity and health status of many aquaculture species. In the present study, a total of 360 juvenile largemouth bass, Micropterus salmoides (19.0 ± 0.1 g) were divided into six experimental groups, and fed diets supplemented with varying levels of crystalline L-threonine at 0 g kg−1 (control), 2.5 g kg−1 (Thr-2.5), 5.0 g kg−1 (Thr-5.0), 7.5 g kg−1 (Thr-7.5), 10.0 g kg−1 (Thr-10.0) and 12.5 g kg−1 (Thr-12.5) for eight weeks. The results revealed that white blood cell count (P = 0.024) and albumin content (P = 0.006) in fish were significantly modulated by the dietary threonine, with the highest levels recorded in fish fed diets Thr-5.0 and Thr-12.5, respectively. White blood cell increased with dietary threonine levels up to Thr-5.0, then decreased thereafter. The other hematological variables such as red blood cell (P = 0.571), hemoglobin (P = 0.259), hematocrit (P = 0.985), mean corpuscular volume (P = 0.631), mean corpuscular hemoglobin (P = 0.280) and mean corpuscular hemoglobin concentration (P = 0.691) remained unchanged as compared to the control group. Serum lysozyme increased (P = 0.000) with increasing levels of threonine up to 5.0 g kg−1. Fish receiving diet Thr-2.5 had relatively higher (P = 0.000) immunoglobulin M and the level decreased when fed with increasing levels of threonine. The activities of superoxide dismutase (P = 0.008) and malondialdehyde (P = 0.005) were elevated at 10.0 g kg−1 and 12.5 g kg−1 supplementation levels, respectively. Moreover, diets Thr-5.0 and Thr-10.0 induced lower serum alanine aminotransferase (P = 0.011) and aspartate aminotransferase activities (P = 0.000) in fish. These results suggest that threonine supplementation led to a positive effect on the hematology, humoral immunity, antioxidant capacity and liver function enzyme activities of economically important largemouth bass. Therefore, threonine has a clear role in fish nutrition and is important in formulating nutritionally balanced feeds.

The synergistic effects of dietary protein and stocking density on performance, digestive enzymes, and hemato-biochemistry parameters of juvenile striped catfish (Pangasianodon hypophthalmus)

This experiment was designed to examine the impacts of different dietary protein levels (DPLs) and their interaction on the growth and some physiological indices of juvenile striped catfish, Pangasianodon hypophthalmus, reared at different stocking densities (SDs) for 15 weeks. A total of 1440 striped catfish (initial weight = 10.0 ± 2.2 g) were randomly allocated into six equal treated groups (three replicates per treated group). Fish were fed two DPLs of 25 % and 30 % and reared under different SDs of 20, 40, and 60 fish/m3. The obtained results indicated that with increasing DPL, growth parameters, and digestive enzyme activities, the liver function enzyme activities, serum protein constituents' levels, and concentrations of thyroid hormones significantly increased, while levels of serum glucose, total cholesterol, and triglycerides remarkably decreased. On the other hand, increasing SD negatively affects growth, digestive and liver enzyme activities, some hematological parameters, and fish-body chemical analysis. The interaction between DPLs and different SDs significantly improved the most estimated parameters with increasing DPLs despite intensifying SDs. In general, afforded striped catfish diets containing 30 % DPL and stocked at 20 fish/m3 presented the best performance, consumed feed efficiency, and health status. Thus, the interaction between DPLs and SDs demonstrated the favorable benefits of increasing DPLs by diminishing some of the adverse impacts generated by high SDs, which may subsequently lead to high production and increased revenues for fish farmers.

Metal-amino acid complexes (Zn, Se, Cu, Fe, and Mn) enhance immune response, antioxidant capacity, liver function enzymes, and expression of cytokine genes in Nile Tilapia reared under field conditions.

In the present study, we investigated the effects of partial or total replacement of dietary inorganic trace materials (ITM) with metal-amino acid complexes (MAACs) on immune response, antioxidant capacity, cytokine genes expression, and overall health status of Nile Tilapia Oreochromis niloticus reared in in-pond hapas (mesh cages) under field conditions. All-male Nile Tilapia with an average initial weight of about 90 g fish-1 were stocked into the hapas, in quadruplicates, at a density of 60 fish per hapa (30 fish m-3 ). The fish in each hapa were acclimatized to culture conditions and test diets for 1 week. Water quality parameters, including temperature (°C), pH, dissolved oxygen (mg L-1 ), and total ammonia (mg L-1 ), were monitored regularly. The MAACs were formulated to contain the same mineral concentrations found in the inorganic premix. Metal-amino acid complexes replaced the ITM premix at 0 (control), 25, 50, 75, and 100% levels (Table 1). The diets were fed to caged Nile Tilapia twice a day, for 80 days, at a daily rate of 3% of their body weights. The fish were weighed every 10 days, and the daily rations were readjusted. At harvest, fish in each hapa were collected, counted, and weighed collectively. Five fish from each hapa were rapidly anesthetized, and used for chemical and physiological analyses, including antioxidant and immune response analyses, liver function analysis, and gene expression. The activities of lysozyme, respiratory burst (%), alternative complement (ACH50), phagocytic cells, phenoloxidase, superoxide dismutase, glutathione peroxidase, and liver function enzymes were all improved with increasing supplemental MAACs up to the 50% substitution level. The expression of cytokine genes, including interferon, tumor necrosis factor, interleukin-1, serum alkaline phosphatase, the integrated microbial genomes, chloramphenicol acetyltransferase, and transforming growth factor genes, was significantly upregulated in fish fed on MAAC-supplemented diets compared with the control group. The 50% MAAC level produced the highest upregulation of these genes, whereas gene expression decreased with increasing dietary MAAC levels to 75% and 100%. The quadratic regression analysis indicated that about 60-65% MAAC is required for maximum promotion of immunological and oxidative stress responses, gene expression, and overall health status of Nile Tilapia reared in in-pond hapas under field conditions. Replacement of the ITM premix with a MAAC premix enhanced the immune and antioxidant responses of Nile Tilapia.

Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt

BackgroundTargeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches.MethodsPhytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groupsResultThe lead phytoconstituents of C. sativa extract, Δ-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract (15 mg/kg and 30 mg/kg) respectively gives a 3-fold decrease in the activities of liver function enzymes when compared with the positive control (group 2). It also gives a 1.5-fold decrease in hepatic lipid peroxidation and elevates serum antioxidant enzymes’ activities by 1-fold in HCC treated Wistar rats when compared with the positive control (group 2). In an animal model of hepatocellular carcinoma, C. sativa extract significantly downregulated Akt and HIF mRNAs in groups 3, 4, and 5 with 2, 1.5, 2.5-fold decrease relative to group 2. VEGF mRNA was downregulated by 1.5-fold decrease in groups 3-5 when compared to group 2. The expression of XIAP mRNA was downregulated by 1.5, 2, and 1.25-folds in groups 3, 4, and 5 respectively, in comparison with group 2. In comparison to group 2, COX-2 mRNA levels were downregulated by 1.5, 1, and 1-folds in groups 3–5. In groups 3–5, CRP mRNA was downregulated by 2-fold in comparison with group 2. In groups 3–5, p21 mRNA was upregulated by 2, 2.5, and 3-folds, respectively when compared with group 2. It upregulated p53 mRNA by 2.5, 3.5, and 2.5-folds in groups 3–5 in comparison with group 2. It downregulated AFP mRNA by 3.5, 2.5, .2.5-folds in groups 3, 4, and 5 respectively when compared with group 2. Histologic analysis showed that C. sativa extract reduced necrosis and inflammation in HCC.ConclusionC. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. Its anticancer potential is mediated through antiangiogenic, proapoptotic, cycle arrest, and anti-inflammatory mechanisms.In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored.

Effect of Roselle Flower Extract (Hibiscus sabdariffa Linn.) on Reducing Steatosis and Steatohepatitis in Vitamin B12 Deficiency Rat Model.

Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague-Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&E)-Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.

Origanum majorana L. extract alleviates dexamethasone-induced hepatotoxicity, oxidative stress and pathological alterations in vivo

BackgroundOriganum majorana (O. majorana) is one of the most widely used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, antimutagenic, anticoagulant and beneficial properties. Our study's main goal is to determine how well O. majorana leaf extract can reduce hepatotoxicity and oxidative stress produced by dexamethasone (DXM). Thirty female rats were divided into three groups of ten. Animals in group1 received distilled water daily for eight weeks and served as control. Those in group 2 exposed subcutaneously to 0.1 mg/kg body weight of DXM three times per week for eight weeks and served as the toxic group, while those in group 3 were treated daily and orally with 100 mg/kg of O. majorana aqueous extract + 0.1 mg/kg of DXM three times per week for eight weeks and served as treated group.ResultsDue to DXM treatment, the activities of liver function markers were significantly elevated (P < 0.0001), whereas O. majorana pretreated animals improved or reduced the elevated liver function enzyme activities. Dexamethasone administration considerably enhancing oxidative stress which rose (P < 0.0001) MDA concentration and attenuated the antioxidant defense system by decreasing the activities of GST, GSP, GSR, and CAT significantly in liver homogenate when compared to control animals. The results further demonstrated that pretreatment with O. majorana boosted the antioxidant defenses against the damaging effects of DXM.ConclusionIt can be said that dexamethasone exposure induced- hepatotoxicity and oxidative stress in rats that repaired by O. majorana aqueous extract which had the ability to reduce the impact of hepatic damage. To evaluate the health benefits and safety of O. majorana in individuals, more clinical research is needed.Graphical abstract

Oliveria decumbens Extract Exhibits Hepatoprotective Effects Against Bile Duct Ligation-Induced Liver Injury in Rats by Reducing Oxidative Stress

Background: Cholestasis is described as a disease in which bile flow from the liver is reduced or stopped, and due to its oxidative effects, irreversible consequences may occur. Objectives: Due to the remarkable antioxidant properties of Oliveria decumbens (OD) and the contribution of oxidants to the progression of bile duct ligation (BDL)-induced cholestasis, this research aimed to examine how the OD ethanolic extract affected liver damage and oxidant-antioxidant balance markers in BDL-induced cholestasis. Methods: Forty male Wistar rats weighing 200 - 250 g were used. Cholestasis was induced using the BDL approach. The rats were categorized into four groups: Group 1, sham-control (SC); group 2, cholestatic; group 3, SC + OD; and group 4, cholestatic + OD. A dose of OD ethanolic extract was administered orally (500 mg/kg/day) to rats for seven days. Seven days following surgery, the rats’ blood samples were collected; after sacrifice, a part of the liver tissue was isolated. A histopathological examination was performed, while the rest was stored at -70°C in liquid nitrogen. Heparin-containing tubes were used to gather blood samples. In plasma and hepatic tissue, biochemical tests, histopathological evaluations, and oxidative stress markers staining levels were performed. Results: Our findings showed that OD could effectively reduce liver injury by reducing the activity of liver function enzymes (AST and ALP). At the same time, it did not affect total bilirubin and protein. Bile duct ligation-induced hepatic markers of protein oxidation (PCO) and reactive nitrogen species (NO) were significantly decreased by OD, and it also promoted liver antioxidant capacity by enhancing superoxide dismutase (SOD) activities. Moreover, OD treatment prevented liver bile duct proliferative changes in histopathologic analysis. Conclusions: Our study confirmed that OD exerts substantial hepatoprotective activities against BDL-induced cholestasis by improving liver damage markers and regulating oxidative stress. It may be a beneficial therapeutic agent for managing cholestasis. Bioassay-guided isolation and identification of bioactive OD secondary metabolites can further direct the discovery of potential natural-based drug candidates.

Effects of kiwi fruit (Actinidia chinensis) polysaccharides on metabolites and gut microbiota of acrylamide-induced mice.

Kiwifruit (Actinidia chinensis) has rich nutritious and medicinal properties. It is widely consumed worldwide for the intervention of metabolism disorders, however, the underlying mechanism remains unclear. Acrylamide, a well-known toxic ingredient, mainly forms in high-temperature processed carbohydrate-rich food and causes disorders of gut microbiota and systemic metabolism. This study explored the protective effects and underlying mechanisms of kiwifruit polysaccharides against acrylamide-induced disorders of gut microbiota and systemic metabolism by measuring the changes of gut microbiota and serum metabolites in mice. The results showed that kiwifruit polysaccharides remarkably alleviated acrylamide-induced toxicity in mice by improving their body features, histopathologic morphology of the liver, and decreased activities of liver function enzymes. Furthermore, the treatment restored the healthy gut microbiota of mice by improving the microbial diversity and abundance of beneficial bacteria such as Lactobacillus. Metabolomics analysis revealed the positive effects of kiwifruit polysaccharides mainly occurred through amino and bile acid-related metabolism pathways including nicotinate and nicotinamide metabolism, primary bile acid biosynthesis, and alanine, aspartate and glutamate metabolism. Additionally, correlation analysis indicated that Lactobacillus exhibited a highly significant correlation with critical metabolites of bile acid metabolism. Concisely, kiwifruit polysaccharides may protect against acrylamide-induced toxicity by regulating gut microbiota and metabolism.

Effects of dietary licorice (Glycyrrhiza uralensis) supplementation on growth performance, muscle quality, and immunity in the common carp (Cyprinus carpio haematopterus)

The study aimed to investigate the effects of dietary licorice (Glycyrrhiza uralensis) on the growth performance, muscle quality, and immunity of common carp (Cyprinus carpio haematopterus). Five diets were formulated to contain 0.0%, 0.5%, 1.5%, 2.5%, and 4.0% licorice, respectively. Each diet was randomly distributed to triplicate groups of 60 juvenile (average weight 21.27 ± 0.13 g) per aquarium. After 15 weeks of feeding, the licorice had positive effects on body growth and feed utilization, the FBW, WGR, PER and SGR reached a maximum in the 4.0% treatment group (P < 0.05. Moreover, the qualities of muscle were also improved by licorice including crude protein, the composition of amino acids and fatty acids, especially the highest proportions of DAAs, FAAs and PUFAs were in 0.5% treatment groups (P < 0.05). The activities of liver function enzymes (AST and ALP) in serums did not influence (P > 0.05) by licorice except for significant lower alanine transaminase in 0.5% and 1.5% groups (P < 0.05). However, other serum indices in terms of TG, TC, and HDL were down-regulated or up-regulated after licorice dealing, of which the lowest TG, TC, and the highest HDL were in 0.5%, 1.5%, and 4.0% groups, respectively. In addition, the immunity and oxidant resistance also improved as well as growth performance and muscle quality. Among them, the survival rate of 0.0% and 1.5% groups was the lowest and highest after A. hydrophila dealing, respectively. The licorice diet reduced the mRNA levels of pro-inflammatory cytokines (IL-6, IL-1β) and INOS, but enhanced IL-10 and hepcidin expression (P < 0.05). Meanwhile, the antioxidant enzyme genes (GPX1 and SOD) were also strongly increased by licorice (P < 0.05). Subsequently, the abilities of licorice in pathogenic and oxidant resistance were further checked by Aeromonas hydrophila infection. The levels of cytokines, INOS, hepcidin, GPX1, and SOD were obviously lower than that of the 0.0% groups (P < 0.05), which echoed the decreasing mortality in other licorice treatment groups during A. hydrophila infection. Similarly, the villi height and myenteron thickness were significantly increased with licorice addition (P < 0.05). In summary, the study proves that long-term licorice (5–15 g/kg) addition can improve growth performance, muscle quality, non-specific immunity, antioxidant activity, and A. hydrophila resistance of the common carp. The results lay a foundation for the application of licorice as a safe and effective feed additive in aquaculture.

The role of Bax/Bcl-2 and Nrf2-Keap-1 signaling pathways in mediating the protective effect of boric acid on acrylamide-induced acute liver injury in rats

IntroductionThis study aims to investigate whether boric acid (BA) can protect rats from acrylamide (AA)-induced acute liver injury. Materials and methodsAA was used to induce acute liver injury. Thirty rats were divided into five group including Group 1 (saline), Group 2 (AA), Group 3 (20 mg/kg BA), Group 4 (10 mg/kg BA+AA) and Group 5 (20 mg/kg BA+AA). Their blood and liver were harvested to be kept for analysis. Liver function enzyme activities were performed by spectrophotometric method. Catalase (CAT), superoxide dismutase (SOD) activity, and malondialdehyde levels were determined by colorimetric method. The in-silico studies were performed using the “blind docking” method. ResultsAdministration AA to rats, biochemical parameters, liver histology, and expression levels of apoptotic markers were negatively affected. However, after the administration of BA, the altered biochemical parameters, liver histology, and expression levels of apoptotic markers were reversed. Moreover, the mechanisms of AA-induced deterioration in the levels of SOD, CAT, and Nrf2-Keap-1 and the mechanisms of the protective effect of BA against these deteriorations were explained by in silico studies. ConclusionThus, the present study could explain the interactions between AA and thiol-containing amino acid residues of Keap-1, the effect of BA on these interactions, and the biochemical toxicity caused by the AA. In this sense, this work is the first of its kind in the literature. Based on the biochemical, histopathological, and in silico results, it can be suggested that BA has the potential to be used as a protective agent against AA-induced liver injury.

Morinda lucida stem bark reversed the pattern and extent of lead nitrate-induced liver injury in Wistar rats

Lead toxicity remains one of the most important occupational and environmental health problems with characteristic features that are incompatible with life. Considering the foregoing, we investigated the ameliorative potentials of Morinda lucida stem bark (MLSB) extract on lead nitrate-induced hepatic injury with particular emphasis on its effects on the pattern and extent of lead nitrate toxicity. Thirty-six adult Wistar rats were randomly assigned into six groups (n=6). Normal control group received 2.2mL/kg distilled water only for 4 weeks while hepatic injury was induced by 2-week oral administration of 30mg/kg lead nitrate to experimental rats in the remaining five groups. Following induction, test groups were treated with MLSB for another 2 weeks at 100, 250, and 500mg/kg concentrations respectively while silymarin was administered orally for 2 weeks to positive control group. At the end of the study, serum activities of liver function enzymes and tissue levels of malondialdehyde were determined. Patterns and extent of injury were determined in hematoxylin and eosin-stained section. The result revealed a significant reduction in sera levels of liver function enzymes and tissue level of malondialdehyde (MDA) in extract treated groups. Lead nitrate-induced necrotic changes and other deranged features observed in histological sections were multifocal and they span through multiple zones of hepatic acini (panacinar), MLSB at 250mg/kg concentration reversed by some of these effects. The study concluded that ameliorative property of MLSB could be due to the antioxidant and membrane stabilizing properties of its phenolic compounds.

Assessing the potential toxicity of paint industry effluents to aquatic organisms using the whole effluent testing (WET) approach.

Point source effluent discharges from industries are major sources of pollutants in aquatic ecosystems. In this study, the whole effluent testing approach was used to assess the toxicity of paint industry effluents to fish. Effluents were collected from three paint industries at point of discharge into the environment. Bioassay procedures were used to assess the toxicity of the effluents to fish. Effluent B was the most acutely toxic to the fish with a 96h LC50 value of 3.50% dilution (v/v). The acute toxicity ranking of the effluents to the fish was B > C > A. Analysis of the biochemical parameters of fish exposed to sublethal dilutions of the effluents showed that the three effluents significantly (p < 0.05) enhanced the activities of liver function enzymes and oxidative stress enzymes in exposed fish. The levels of malondialdehyde, a substrate of oxidative stress, was also significantly (p < 0.05) higher in fish exposed to the effluents (3.87 ± 0.40, 4.99 ± 0.45, and 3.22 ± 0.57 U mg-1 protein for effluents A, B, and C, respectively) compared to levels in control (1.24 ± 0.31 U mg-1 protein). Results from this study have established that untreated or poorly treated paint industry effluents can be highly toxic to aquatic organisms, having the potential to disrupt normal functioning of organisms at low concentrations. The study highlights the advantages of whole effluent testing as a method that accurately predicts the toxic potentials of industrial effluents. This is vital for the adequate protection aquatic ecosystems.

Evaluation of in vivo antidiabetic activity of Notonia grandiflora Wall.

The aim of this study was to determine the in vivo hypoglycaemic activity of ethyl acetate extract of Notonia grandiflora (EANG) in albino wistar rats. EANG was orally administrated to STZ (40 mg/kg, i.p, b.w) induced diabetic rats at the doses of 100 and 200 mg/kg b.w for 21 days. The effect of EANG on blood glucose, body weight, plasma insulin, urea, uric acid, creatinine, Hb, HbA1C, liver glycogen content, bilirubin level, liver enzymes (Serum glutamate pyruvate transaminases, serum glutamate oxaloacetate transaminases, alkaline phosphatase) were measured in the diabetic rats. Treatment of EANG significantly lowered the levels of blood glucose and glycosylated haemoglobin. It also restored body weight, liver glycogen content, and serum insulin level in diabetic rats in a dose-dependent manner. A significant reduction in the activity of liver function enzymes associated with diabetes and serum levels of renal parameters after treatment with EANG was observed, signifying the protective effects of EANG in diabetes-associated complications. Hence, it could be used as a safer complementary drug in the management of diabetes and associated complications.

Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems.

Diethyl nitrosamine (DEN) induced cirrhosis-hepatocellular carcinoma (HCC) model associates cancer progression with oxidative stress and mitochondrial dysfunction. This study investigated the effects of mitoquinol mesylate (MitoQ), a mitochondrial-targeted antioxidant on DEN-induced oxidative damage in HCC Wistar rats. Fifty male Wistar rats were randomly divided into five groups. Healthy control, DEN, and MitoQ groups were orally administered exactly 10mg/kgof distilled water, DEN, and MitoQ, respectively for 16weeks. Animals in the MitoQ + DEN group were pre-treated with MitoQ for a week followed by co-administration of 10mg/kg each of MitoQ and DEN. DEN + MitoQ group received DEN for 8weeks, then co-administration of 10mg/kg each of DEN and MitoQ till the end of 16th week. Survival index, tumour incidence, hematological profile, liver function indices, lipid profile, mitochondrial membrane composition, mitochondrial respiratory enzymes, and antioxidant defense status in both mitochondrial and post-mitochondrial fractions plus expression of antioxidant genes were assessed. In MitoQ + DEN and DEN + MitoQ groups, 80% survival occurred while tumour incidence decreased by 60% and 40% respectively, compared to the DEN-only treated group. Similarly, MitoQ-administered groups showed a significant (p<0.05) decrease in the activities of liver function enzymes while hemoglobin concentration, red blood cell count, and packed cell volume were significantly elevated compared to the DEN-only treated group. Administration of MitoQ to the DEN-intoxicated groups successfully enhanced the activities of mitochondrial F1F0-ATPase and succinate dehydrogenase; and up-regulated the expression and activities of SOD2, CAT, and GPx1. Macroscopic and microscopic features indicated a reversal of DEN-induced hepatocellular degeneration in the MitoQ + DEN and DEN + MitoQ groups. These data revealed that MitoQ intervention attenuated DEN-induced oxidative stress through modulation of mitochondrial antioxidant defense systems and alleviated the burden of HCC as a chemotherapeutic agent.

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation.

Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl4)-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl4-induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.

Antidiabetic effect of Wedelia chinensis leaf extract in alloxan induced Swiss albino diabetic mice

BackgroundWedelia chinensis (W. chinensis) is a beneficial medicinal herb used in folk medicine to treat many chronic diseases. The present study is aimed to evaluate the antidiabetic property of methanolic extract of W. chinensis leaf (MEWL) in alloxan induced Swiss albino diabetic mice.MethodsMethanol was used as a solvent to obtain W. chinensis leaf extract. In vitro antidiabetic property of MEWL was revealed by α-amylase and α-glucosidase inhibition assays. To explore in vivo antidiabetic properties of MEWL, diabetes was induced in Swiss albino mice by intraperitoneal injection of alloxan at dose of 80 mg/kg body weight (BW). All Swiss albino mice (normal mice and diabetic mice) were divided into five groups and orally treated with normal pellet diet and water (normal control and diabetic control), glibenclamide 5 mg/kg BW and MEWL (100 and 200 mg/kg BW). Effects of MEWL on blood glucose levels, activity of liver function enzymes associated with diabetes and serum levels of lipid parameters were evaluated.ResultsIn α-amylase inhibition assay, 48.39% inhibition in the activity of α-amylase was observed at 500 μg/ml concentration of MEWL. Moreover, 39.37% inhibition of α-glucosidase activity was observed at 10 μg/ml concentration of MEWL. The results of in vivo antidiabetic assays showed that MEWL significantly (p < 0.01) decreased blood glucose level and ameliorated parameters of lipid profile (TG, TC, LDL, VLDL and HDL) in diabetic mice. MEWL treatments for 21 days also reduced the activity of SGPT and SGOT enzymes, and CRP levels in the serum of diabetic mice significantly (p < 0.01) compared to that of untreated diabetic mice.ConclusionThe present study demonstrated that W. chinensis leaf extract effectively subsidized the hyperglycemic effect along with restoring the lipid profile parameters in diabetic mice and might be used as an alternative medicine for the management of diabetes.

Mitoubiquinol Mesylate Attenuated Diethyl Nitrosamine–Induced Hepatocellular Carcinoma Through Modulation of Mitochondrial Antioxidant Defense Systems

PURPOSE Hepatocellular carcinoma (HCC) is a highly malignant cancer, with a high recurrence rate and a poor prognosis. Diethyl nitrosamine (DEN) cirrhosis HCC–induced model has revealed an association of cancer progression with oxidative stress and mitochondrial dysfunction. This study investigated the effects of mitoubiquinol mesylate (MitoQ), a mitochondrial targeted antioxidant derivative from ubiquinone on DEN-induced oxidative damage in HCC Wistar rats. METHODS Fifty male Wistar rats were randomly divided into 5 groups, 10 rats per group. Groups A, B, and C received distilled water 10 mL/kg DEN, and MitoQ orally for 16 weeks, respectively. Animals in group D were pretreated with MitoQ for 1 week followed by coadministration of MitoQ and DEN (protective effect), whereas group E received DEN for 8 weeks, then coadministration of DEN and MitoQ (therapeutic effect) until the end of the study. Survival index, tumor incidence, liver function indices, hematologic profile, mitochondrial respiratory enzymes, and antioxidant defense status were assessed. RESULTS Data obtained show that rats in groups D and E had 80% survival and decreased tumor incidence (40% and 60%, respectively) compared with group B. Similarly, MitoQ significantly ( P &lt; .05) decreased the activities of liver function enzymes, while hemoglobin concentration, red blood cell count, and lymphocytes levels were significantly elevated compared with the DEN-only group. Furthermore, MitoQ significantly ( P &lt; .05) protected the liver from DEN-induced oxidative damage; however, there was no significant difference ( P &gt; .05) between activities of mitochondrial F1F0-ATPase and succinate dehydrogenase of groups A, B, D, and E, respectively, although these enzyme activities were significantly ( P &lt; .05) elevated in group C. Macroscopic and microscopic features indicated a reversal of DEN-induced cellular degeneration in hepatocytes. CONCLUSION These data suggest that MitoQ treatment for 16 weeks attenuated DEN-induced oxidative stress indices via modulation of mitochondrial antioxidant defense systems and could alleviate the burden of HCC as a chemotherapeutic agent.

Dietary oregano essential oil improved the growth performance via enhancing the intestinal morphometry and hepato-renal functions of common carp (Cyprinus carpio L.) fingerlings

The current work was designed to assess the influences of dietary oregano essential oil (OEO) on the indices of growth and feed utilization, proximate composition, hepato-renal functions, and histomorphological criteria of livers, kidneys, and intestines of common carp (Cyprinus carpio L.) fingerlings. Fish (20.3 ± 0.8 g) were randomly divided into five treatments and fed on different levels of OEO at 0, 5, 10, 15, and 20 g/kg diet for 2 months. The results showed that the dietary OEO significantly improved the growth parameters (final body weight, weight gain, weight gain %, specific growth rate, and feed intake) (P < .05) in a dose-dependent regime; meanwhile, the feed conversion ratio was not affected with respect to the control group. The body proximate composition and survival rates were not significantly affected. The serum protein profile (total protein, albumin, and globulin), activities of liver function enzymes (alanine transaminase aspartate transaminase, and alkaline phosphatase), and renal markers (creatinine and urea) were not significantly altered (P < .05) by OEO supplementation. The histomorphology of hepatopancreatic and renal tissues of common carp fed OEO at varying levels were correlated with the serum hepato-renal functions without any noticed pathologic lesions. Moreover, the intestinal villi with associated goblet cells and crypt, tunica muscularis (both internal and external muscular layers) and submucosal tissues appeared free of inflammatory and/or degenerative changes. All intestinal morphometric measurements revealed a significant improvement (P < .05) in OEO-fed fish in comparison with the control one. Conclusively, in common carp, the dietary OEO improved growth performance and intestinal histomorphology with no inflammatory signs, and with potential hepato-protective effects with the optimum level of 15 g/kg diet. These beneficial effects were possibly because of OEO-mediated beneficial improvements in the histomorphometric criteria of the fish intestines.

Moringa oleifera leaf extract ameliorated high-fat diet-induced obesity, oxidative stress and disrupted metabolic hormones

BackgroundObesity is a health problem in many countries, and maintaining a perfect weight is challenging. Moringa oleifera leaf extract (ME) is rich in polyphenols with antioxidant and pharmaceutical potential. The present study investigated the potential protective effect of Moringa oleifera leaf extract against obesity induced from a high-fat diet (HFD), oxidative stress and disruption of metabolic hormones compared to simvastatin (SIM) or their combination.ResultsRats fed a HFD for 6 weeks exhibited a significant increase in body weight and levels of serum glucose and lipid fractions, verifying an obesity state. There were also higher levels of insulin and leptin and lower gherlin in sera of HFD rats compared to the levels in control rats. Homeostasis model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the atherogenic index were elevated, indicating the development of insulin resistance and dyslipidaemia in these rats. These changes were accompanied with a significant increase in oxidative stress, as indicated by elevated lipid peroxidation and protein oxidation with low levels of antioxidants in liver. The activities of liver function enzymes, including aspartate amino transferase, alanine amino transferase, alkaline phosphatase and gamma glutamyltransferase, were also significantly increased in serum. Concurrent treatment with 300 mg/kg ME for 6 weeks ameliorated the increase in body weight and improved the levels of glucose, lipid fractions and metabolic hormones, indicating the anti-obesity effect and amelioration of tissue insulin resistance potential of ME. ME treatment also normalized oxidative stress and antioxidants in liver and improved liver function enzymes, indicating the antioxidant potential of ME. The effects of ME were similar to SIM, and the combination of these agents was better than each agent alone.ConclusionWe propose that ME extract has anti-obesity and antioxidant potential and may be used as a lipid-lowering drug to control weight, obesity and its pathophysiological consequences.

Thymus vulgaris extract modulates dexamethasone induced liver injury and restores the hepatic antioxidant redox system

BackgroundThe liver is the largest important organ and the site for essential biochemical reactions and detoxifying toxic substances in the human body. Long-term, high-dose dexamethasone administration can cause severe alterations in liver function. Therefore, Thymus vulgaris leave extract possess a modulatory role on dexamethasone-induced hepatotoxicity by attenuating antioxidant defense system.By subcutaneous route, animals will receive three doses per week for 8 weeks of dexamethasone (0.1 mg/kg. b. wt.) concomitant with oral administration of thyme aqueous extract (500 mg/kg b.wt.).ResultsDXM treatment led to a marked increase in the liver function enzyme activities that are successfully ameliorated by thyme aqueous extract. Thyme natural antioxidants augmented the antioxidant defense system that overcomes oxidative stress caused by dexamethasone. Conversely, although dexamethasone-treated animals rose lipid peroxidation, thyme extract pretreatment did the reverse.ConclusionHepatotoxicity and oxidative stress caused by dexamethasone might improve by thyme natural antioxidants.