Hepatic Malondialdehyde Levels Research Articles

Genistein and exercise modulated lipid peroxidation and improved steatohepatitis in ovariectomized rats

BackgroundThe prevalence of nonalcoholic steatohepatitis (NASH) in menopausal women is increasing, but current treatments have not been proven effective. The objective of this study was to investigate the treatment effects of genistein and running exercise in ovariectomized (OVX) rats with NASH.MethodsThirty-six female Sprague-Dawley rats were divided into 6 groups, control; OVX with standard diet; OVX with high fat and high fructose (HFHF) diet for 4 weeks; OVX with HFHF and genistein treatment (16 mg/kg BW/day) for 5 weeks (OVX + HFHF+GEN); OVX with HFHF and moderate intensity exercise for 5 weeks (OVX + HFHF+EX); OVX with HFHF and combined treatments (OVX + HFHF+GEN + EX). Serum interleukin-6 (IL-6) levels, hepatic free fatty acid (FFA), hepatic glutathione (GSH), and hepatic malondialdehyde (MDA) levels were measured. Liver histology was examined to determine NASH severity.ResultsOVX + HFHF group had the highest levels of hepatic FFA compared with OVX and control groups (5.92 ± 0.84 vs. 0.37 ± 0.01 vs. 0.42 ± 0.04 nmol/mg protein, respectively, p < 0.01). Serum IL-6 levels were significantly elevated in both OVX and OVX + HFHF groups as compared with controls (112.13 ± 6.50 vs. 121.47 ± 3.96 vs. 86.13 ± 2.40 pg/mL, respectively, p < 0.01). In OVX + HFHF group, hepatic MDA levels were higher, while GSH levels were lower than in OVX and control groups (MDA; 0.98 ± 0.04 vs. 0.82 ± 0.02 vs. 0.78 ± 0.03 nmol/mg protein, and GSH; 46.01 ± 0.91 vs. 55.21 ± 1.40 vs. 57.94 ± 0.32, respectively; p < 0.01 for both). Comparing with OVX + HFHF group, rats that received genistein, exercise and combined treatments demonstrated an improvement in liver histopathology, decreased levels of hepatic FFA (1.44 ± 0.21 vs. 0.45 ± 0.04 vs. 0.49 ± 0.05 nmol/mg protein, respectively, p < 0.01), serum IL-6 (82.80 ± 2.07 vs. 83.47 ± 2.81 vs. 94.13 ± 1.61 pg/mL, respectively, p < 0.01), and hepatic MDA (0.80 ± 0.03 vs. 0.76 ± 0.02 vs. 0.76 ± 0.03 nmol/mg protein, respectively, p < 0.01).ConclusionsGenistein and moderate intensity exercise were effective in reducing the severity of NASH in OVX rats through the reduction in liver inflammation, oxidative stress and liver fat contents.

Sexually Dimorphic Responses to a High-Refined Carbohydrate Diet in a Nonalcoholic Fatty Liver Disease Mouse Model

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD) incidence and prevalence have been reported to be higher in men than women, however, the effects of sexual dimorphism on NAFLD risk and progression have not been adequately examined. Our lab has previously shown that a liquid high-refined carbohydrate diet (HRCD) induced more severe hepatic steatosis compared to an isocaloric high fat diet in male mice. Also, HRCD-induced reduction in sirtuin 1 (SIRT1), an NAD-dependent deacetylase protein, has previously been implicated in NAFLD pathogenesis. Therefore, we investigated whether there were sexually dimorphic responses to a liquid high-refined carbohydrate diet (HRCD) in male and female, wildtype and SIRT1-deficient mice. Methods Male and female 10–12-week-old wildtype (SIRT1 +/+: n = 12; M = 6, F = 6) and mice carrying a heterozygous H355Y SIRT1 point mutation (SIRT1 +/y: n = 14; M = 7, F = 7) were both fed a HRCD (Lieber-DeCarli liquid diet supplemented with maltose dextrin; 47% energy from refined carbohydrate, Dyets, #710,260) for 5 weeks and 9 weeks. Hepatic gene expression was examined using qRT-PCR. Plasma ALT (alanine transaminase) and hepatic MDA (malondialdehyde) levels were determined using colorimetric assay kits. Hepatic steatosis scoring was conducted by analyzing Hematoxylin and Eosin (H&amp;E) stains. Results 9 weeks of HRCD induced significantly less hepatic steatosis in female mice irrespective of genotype compared to male mice as determined by grading of H&amp;E stains (P &amp;lt; 0.05). Furthermore, liver expression of several fatty acid oxidation genes (CPT1, ACOX1) was significantly higher in females (P &amp;lt; 0.05), which potentially suggests increased fatty acid oxidation. Additionally, female mice had significantly increased antioxidant gene expression (GPX4, SOD1, SOD2, Catalase) and significantly lower hepatic MDA (P &amp;lt; 0.05), which indicate an increased capacity to mitigate oxidative stress. Lastly, plasma ALT levels were significantly lower in females compared to males after 9 weeks of HRCD (P &amp;lt; 0.05). Conclusions Collectively, these data indicate that female mice are moderately protected against HRCD-induced NAFLD compared to male mice, potentially through increased hepatic fatty acid oxidation and superior mitigation of oxidative stress due to increased antioxidant system gene expression in the liver. Funding Sources HNRCA, USDA/ARS Grants.

Hepatoprotective effects of dietary Artemisia (Artemisia annua) leaf extract on common carp (Cyprinus carpio) exposed to ambient ammonia

In this study, antioxidant capacity of Artemisia (Artemisia annua) leaf extract (AE) were assessed, in vitro, followed by evaluation of dietary AE administration on hepatic health of common carp (Cyprinus carpio), during ammonia exposure. For this, common carp juveniles were fed diets supplemented with 0, 0.5, 1 and 2 g kg−1 AE for 30 days and then, exposed to 0.5 mg L−1 water unionized ammonia nitrogen for 24 h. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total protein, as well as hepatic levels of malondialdehyde (MDA), and activity and gene expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were monitored. The results showed that AE had antioxidant properties, in vitro. Moreover, Dietary AE administration had no significant effects on plasma ALT, AST and ALP activities before ammonia exposure, but mitigated the enzymes elevation after the ammonia exposure. Dietary AE administration significantly increased plasma total protein before the ammonia exposure and mitigated/inhibited the ammonia-induced hypoproteinemia. In addition, the fish fed with the AE-supplemented diets showed higher hepatic antioxidant enzyme activity and gene expression and lower hepatic MDA levels, before the ammonia exposure. AE significantly mitigated/inhibited the ammonia-induced increase in hepatic antioxidant enzymes activities and gene expressions as well as hepatic MDA levels. In conclusion, AE is suitable antioxidant agent and can be used as feed additive to prevent hepatotoxicity of common carp during ammonia exposure.

Panaxynol from Saposhnikovia diviaricata exhibits a hepatoprotective effect against lipopolysaccharide + D-Gal N induced acute liver injury by inhibiting Nf-κB/IκB-α and activating Nrf2/HO-1 signaling pathways

ABSTRACT We investigated the mechanism of action of panaxynol (PAL) extract from the root of Saposhnikovia diviaricata (Turcz.) Schischk for treating acute liver injury caused by lipopolysaccharide (LPS) and D-galactosamine (D-Gal N) in mice. A mouse model of acute liver failure induced by LPS/D-Gal N was established. Mice were divided randomly into three equal groups: control group, LPS/D-Gal N group and PAL group. After seven days of continuous PAL administration, all animals except controls were injected with 50 μg/kg LPS and 800 mg/kg D-Gal N; blood and liver samples were collected after 8 h. Compared to the LPS/D-Gal N group, the levels of catalase, glutathione and superoxide dismutase were increased in the liver of the PAL group. The inflammatory response index indicated that PAL attenuated LPS/D Gal N-induced liver pathological injury and decreased levels of hepatic malondialdehyde, serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α, and interleukins 1β and 6. PAL also inhibited LPS/D-Gal N induced nuclear factor-kappa B (Nf-κB), inhibitor kappa B-α (IκB-α) activation, and up-regulated Nrf2 and heme oxygenase-1 (HO-1) expression. PAL can prevent LPS/D-Gal N induced acute liver injury by activating Nrf2/HO-1 to stimulate antioxidant defense and inhibit the IkB-α/NF-κB signaling pathway.

Association of long-term consumption of repeatedly heated mix vegetable oils in different doses and hepatic toxicity through fat accumulation

BackgroundHepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation.MethodsIn this study, healthy adult male rabbits of local strain were divided into 4 groups (n = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups.ResultsSignificantly (p < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40–60% increased oxidative stress compared to control, in a dose-dependent manner.ConclusionsThese results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.

PROTECTIVE EFFECT OF AQUEOUS EXTRACT OF LEAVES OF MURRAYA KOENIGII, AGAINST ALUMINUM CHLORIDE-INDUCED OXIDATIVE STRESS IN RAT LIVER AND KIDNEY

Objective: The aim of the current study was to investigate the hepatoprotective, nephroprotective, and cholesterol-lowering activity of aqueous extract of Murraya koenigii (MK) leaves against AlCl3-induced oxidative stress in rats.&#x0D; Methods: Wistar albino rats were distributed into six groups (6 each). Group I (control), and Group II administered with distilled water, and aluminum chloride (AlCl3), (40 mg/kg body weight [b.w], oral), respectively. Group III rats were treated with standard Vitamin E (100 mg/kg b.w, p.o) and AlCl3 (40 mg/kg b.w, oral). Group IV, V, and VI received aqueous extract of leaves of Murraya koenigii (AEMK) (100 mg/kg b.w, peroral [p.o], 200 mg/kg b.w, p.o, and 400 mg/kg b.w, p.o), respectively, for a period of 35 days.&#x0D; Results: Histopathological examination was observed deformities in hepatic and renal tissues due to aluminum exposure which augment the aforementioned results. Coadministration of AEMK along with Al significantly restored the serum biomarkers to their near-normal levels and has the ability to overcome Al-induced oxidative stress, manifested by a significant reduction in hepatic and renal malondialdehyde level. It increased cellular antioxidant defense, particularly by increasing GPx, glutathione, GR, and catalase levels, preserved normal hepatic and renal histological architecture.&#x0D; Conclusion: It could be concluded that AEMK has significant radical scavenging activity and can mop up Al-induced toxicity, suggesting hepatoprotective and nephroprotective potential.

Tamarix chinensis Lour inhibits chronic ethanol-induced liver injury in mice.

BACKGROUNDTamarix chinensis Lour (TCL) is a shrub that usually grows in arid or semiarid desert areas and saline-alkali fields. It is a traditional Chinese herbal medicine with hepatoprotective, antioxidant, antibacterial, and antitumor activities.AIMTo investigate the possible protective effects of TCL against liver injury induced by chronic ethanol intake.METHODSC57BL/6J male mice were fed a Lieber-DeCarli lipid diet containing alcohol and received (by gavage) a water-alcohol extract (80%) of TCL (100 and 200 mg/kg BW) or distilled water for 4 wk. After euthanasia, liver tissues were observed histologically with hematoxylin and eosin staining and Oil red O staining, and the levels of alanine aminotransferase, aspartate transaminase, hepatic lipids, reactive oxygen species, malondialdehyde, and superoxide dismutase were measured. In addition, expression of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and downstream proinflammatory cytokines were determined.RESULTSCompared with the ethanol group, mice in the TCL-treated group (200 mg/kg) had significantly lower serum levels of alanine aminotransferase (mean, 34.1 IU/L vs 45.3 IU/L, P < 0.01) and aspartate transaminase (mean, 89.6 IU/L vs 115.7 IU/L, P < 0.01), as well as marked reduction of hepatic tissue reactive oxygen species (decreased by 27.5%, P < 0.01) and malondialdehyde (decreased by 76.6%, P < 0.01) levels, with a significant increase of superoxide dismutase (Increased by 73.2%, P < 0.01). Expression of the NLRP3 inflammasome and its downstream cytokines [interleukin (IL)-1β, tumor necrosis factor-α, and IL-6], and recruitment of natural killer T cells to the liver, were reduced in the TCL-treated incubation with a Lieber-DeCaril ethanol lipid diet group.CONCLUSIONThese findings suggest that a TCL extract (200 mg/kg) protects against chronic ethanol-induced liver injury, probably by inhibiting the NLRP3-caspase-1-IL-1β signaling pathway and suppressing oxidative stress.

Hepatoprotective and Antioxidant Capacity of Mallotus repandus Ethyl Acetate Stem Extract against d-Galactosamine-Induced Hepatotoxicity in Rats.

Mallotus repandus (M. repandus) is traditionally used to treat muscle pain, itching, fever, rheumatic arthritis, and a variety of liver disorders. The aim of the present work was to evaluate the hepatoprotective activity and the antioxidant potential of the ethyl acetate stem extract of M. repandus (ESMR) against d-galactosamine (d-GalN)-induced hepatopathy, along with a possible mechanism of action in rats. In vivo hepatoprotective activity of ESMR was examined using d-galactosamine (d-GalN)-induced hepatotoxicity in Sprague–Dawley rats. For this purpose, levels of serum diagnostic markers, activity of hepatic antioxidant enzymes, and liver histo-architecture were employed to assess the protective efficacy of ESMR. Furthermore, the total phenolic, flavonoid, and tannin contents were quantitated, and the antioxidant capacity of the extract was evaluated using different methods such as 2,2′-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H2O2), and hydroxyl radical (OH•) scavenging assays. Intraperitoneal d-GalN injection triggered hepatotoxicity, as shown by the noticeable increase in the serum hepatic marker enzymes, bilirubin content, γ-glutamyl transferase (GGT), total cholesterol (TC), triglycerides (TGs), and malondialdehyde (MDA), whereas glutathione, superoxide dismutase, and catalase levels were significantly lower compared with that of the control. Pretreatment with ESMR reduced the hepatic enzyme levels along with bilirubin, GGT, and MDA compared to the d-GalN-intoxicated group. These results were supported by histopathological studies, where d-galactosamine caused coagulative necrosis, hemorrhage, and inflammation. However, pretreatment with ESMR ameliorated the histo-architectural changes and brought them back to normal. Results also revealed that the total polyphenolic, flavonoid, and tannin content, and total antioxidant capacity of ESMR were 136.30 ± 0.78 mg GAE/g mg, 38.72 ± 0.85 mg QE/g, 75.88 ± 0.54 mg TAE/g, and 123.16 ± 0.24 mg AAE/g, respectively. In addition, ESMR inhibited free radicals with IC50 values of 94.47 ± 0.51, 127.33 ± 0.36, 164.12 ± 0.45, and 254.14 ± 0.35 μg/mL in DPPH, NO, H2O2, and OH• free radical scavenging assays, respectively. These findings highlight the protective role of ESMR against hepatic injury induced by d-GalN, which may be attributed to its higher antioxidant properties, thereby scientifically justifying its traditional use.

Possible Protective Effect of Onion Supplementation on Hepatic Functional and Structural Alterations Induced by Cholestasis

Abstract Background Cholestasis is the obstruction or the reduction in bile flow that results in intrahepatic accumulation of bile constituents, which progresses to develop liver pathology. Common bile duct ligation (BDL) in rodents is an experimental model of cholestasis that has been carried out in research for many years. BDL model of cholestatic liver injury involves other mechanisms, including oxidative stress, inflammation, and fibrogenesis. Antioxidant, antiinflammatory or antiapoptotic properties gained much interest for the amelioration of liver dysfunction. Aim the aim of this study is to assess the possible protective effects of onion supplementation on hepatic structural and functional alterations induced by BDL in rats, which reflect the effects of cholestasis resulting from intrahepatic accumulation of bile. Methods Thirty adult female Wistar rats were randomly and equally allocated into three groups: (1) control group, (2) BDL group; subjected to ligation of the common bile duct and (3) Onion-supplemented BDL groups (O-BDL). Both control and BDL groups received distilled water (solvent for onion powder) daily by gavage for 4 weeks. Onion-supplemented BDL group (O-BDL); subjected to ligation of the common bile duct and then received 500 mg/kg of onion powder dissolved in distilled water, daily by gavage for 4 weeks. At the end of the experimental period, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct bilirubin, total proteins, total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), and hepatic tissue level of malondialdehyde (MDA) and transforming growth factor-β (TGF-β) were measured for all groups. In addition, histopathological examination of liver tissue samples was performed for the three groups. Results Plasma levels of ALT, AST, ALP, direct bilirubin, TNF-α and hepatic tissue levels of MDA and TGF-β were significantly increased and TAC was significantly decreased in the BDL group compared to the control group. In addition, altered architecture was detected in hepatic tissue samples of BDL group. Onion supplementation significantly decreased the plasma levels of ALT, AST, ALP, direct bilirubin, TNF-α and hepatic tissue levels of MDA and TGF-β in the O-BDL group when compared to the BDL group. Total proteins level was not significantly different among all the studied groups. In addition in O-BDL group, histopathological examination of liver revealed near normal structure of hepatic tissue. Conclusion BDL induces hepatic structural alterations and functional disturbances. Onion supplementation inhibits inflammation and oxidative insults that associate BDL, and subsequently protects against BDL-induced liver injury.

Weaning Mice and Adult Mice Exhibit Differential Carbon Tetrachloride-Induced Acute Hepatotoxicity.

Age is a risk factor for drug-induced liver injury (DILI). However, there is a limited understanding of pediatric DILI. Here, 2-week-old weaning and 8-week-old adult male ICR mice were intraperitoneally injected with CCl4 (0.1 mmol/kg equal to 15.4 mg/kg) to comparatively evaluate the time-dependent liver damage and cellular events. CCl4 significantly enhanced the serum alanine aminotransferase/aspartate aminotransferase levels and hepatic centrilobular necrosis in the weaning mice, whereas it induced mild liver injury in the adult mice. CCl4-treated weaning mice exhibited higher hepatic levels of pro-apoptotic proteins (Bax, cleaved caspase-3, -7, and -9), activated MAPKs (p-JNK and p-Erk), and endoplasmic reticulum stress indicators (ATF6 and CHOP) and lower hepatic anti-apoptotic Bcl-2 levels than the adult mice. The weaning mice exhibited enhanced basal hepatic glutathione (GSH) levels due to high glutamate cysteine ligase (GCL) and low anti-cysteine dioxygenase (CDO) enzyme levels. However, CCl4 markedly reduced the hepatic GSH levels only in the weaning mice. Furthermore, higher hepatic levels of oxidative stress-induced malondialdehyde, 4-hydroxynonenal, nitrotyrosine-protein adducts, and oxidized proteins were observed in CCl4-treated weaning mice than in CCl4-treated adult mice. The enhanced levels of hepatic cytochrome P450 (CYP) 2E1 and CYP3A, and decreased hepatic GSH S-transferase (GST)-π and GSH reductase (GR) levels in the weaning mice may contribute to their enhanced susceptibility to liver damage.

Fat powder can be a feasible lipid source in aquafeed for the carnivorous marine teleost golden pompano, Trachinotus ovatus

In the production of aquafeeds, exogenous liquid oils are usually added directly or by vacuum coating. In order to evaluate the practicality of fat powder in aquafeeds and aquaculture, four isoproteic (46%) and isolipidic (12%) diets named FOl, BOl, FOp, and BOp were prepared with fish oil (FO) or blend oil (BO, consisting of fish, soybean, rapeseed, and perilla oils) or their corresponding fat powder as dietary lipid, respectively. Each diet was fed to triplicate groups of golden pompano Trachinotus ovatus juveniles (initial body weight about 15.10 g) in floating sea cages (1.0 × 1.0 × 2.0 m, 30 fish per cage) for 10 weeks. Fish were fed to nearly satiation at two times each day. The results showed that the final weight, weight gain rate (WGR), specific growth rate (SGR), food conversion ratio (FCR), condition factor (CF), viscerosomatic index (VSI), and survival rate (SUR) displayed no significant difference among the four dietary groups (P > 0.05), while the hepatosomatic index (HSI) in the BOp group (1.01) was significantly lower than that in FO-base groups (1.19–1.23) (P < 0.05). The fatty acid (FA) composition in livers or dorsal muscle showed no difference between the fish fed the diets from liquid oil and corresponding fat powder. A significantly high serum alkaline phosphatase (ALP) activity and low hepatic malondialdehyde (MDA) level were detected in the BOp group (P < 0.05). Moreover, the mRNA levels of hepatic glutathione peroxidase (gsh-px), superoxide dismutase (sod), and catalase (cat), as well as intestinal FA binding protein 2 (fabp2) and FA transport protein 4 (fatp4) genes in one or both of the fat powder groups, were significantly higher than those in the corresponding liquid oil groups (P < 0.05). Additionally, the peroxide value (POV) and MDA level in FOp and BOp diets were less than 27% of those in FOl and BOl diets after stored at − 20 °C for 3 months. These results demonstrated that fat powder diets, especially BOp, displayed better effects than liquid oil diets in lipid oxidation stability, liver health, and FA transportation in T. ovatus, which indicated that fat powder can be a feasible lipid source in aquafeed. To our knowledge, this is the first report on the practical application of fat powder in aquaculture, which may provide a new form of lipid addition in the aquafeeds industry.

Components identification and nutritional value exploration of tea (Camellia sinensis L.) flower extract: Evidence for functional food

Camellia sinensis L., its fresh leaves and buds are used to make tea, is an important industrial crop with a long history. However, less attention has been paid to tea flowers. Indeed, tea flower extract (TFE) is a rich source of functional molecules, but its nutritional value remains unclear. This study, from the perspective of “whole food”, aimed to investigate the composition of TFE and further explore its possible health-promoting effects on cyclophosphamide-induced mice. It was found that TFE was mainly composed of carbohydrates (34.02 ± 1.42%), phenolic compounds (11.57 ± 0.14%), crude proteins (27.72 ± 3.07%) and saponins (2.81 ± 0.00%). Supplementation of TFE at 200 mg/kg·BW/d regulated intestinal homeostasis by improving the intestinal barrier, alleviating dysbacteriosis (reverse 44 of 68 disordered genera), stimulated immunoreactions with significant enhancement of serum TNF-α, IFN-γ, IL-1β, IL-2 and IL-6. Furthermore, TFE could improve the liver function through decreasing the hepatic malondialdehyde and aminotransferase levels and increasing the levels of catalase, myeloperoxidase, superoxide dismutase and reduced glutathione. Notably, the ameliorating effects of TFE on cyclophosphamide-induced immunosuppression and the hepatic injury were associated with its modulation of gut microbiota. The results provide the evidence for the application of tea flower as potential functional food.

A novel acidic polysaccharide from the residue of Panax notoginseng and its hepatoprotective effect on alcoholic liver damage in mice

This study presented the first purification and characterization of a hepatoprotective polysaccharide (PNPS-0.5 M) from the residue of Panax notoginseng (Burk.) F.H. Chen. This polysaccharide included a backbone of (4 → 1)-linked GalA and branches of (1→)-linked Araf, (1→)-linked Rhap, and (5 → 1)-linked Araf and had an extremely high molecular weight (2600 kDa). We investigated the hepatoprotective effects of PNPS-0.5 M on mice with alcoholic liver damage (ALD). After administration of PNPS-0.5 M, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and hepatic malondialdehyde (MDA) were reduced to normal. In contrast, hepatic levels of alcohol dehydrogenase (ADH) and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated to normal. Further investigations indicated that PNPS-0.5 M activated Nrf2 signaling as a protective mechanism against Cyp2e1 toxicity in ALD mice. Meanwhile, it strengthened the ADH pathway and suppressed the CAT pathway of alcohol metabolism to prevent peroxide accumulation, thereby ameliorating ALD. In the present study, we describe a novel acidic polysaccharide from P. notoginseng with hepatoprotective activity that facilitates the development and utilization of P. notoginseng resources.

C-reactive Protein Signaling and Chromosomal Abnormalities in Nanotoxicity Induced via Different Doses of TiO2 (80nm) Boost Liver Function.

The wide application of nanotechnology merits the need to clarify their nanotoxicity. In vivo studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2 NPs), but there are limited data on chromosomal abnormalities induced in hepatic tissue. In this article, the toxicity of three IP doses of TiO2 NPs (80nm) (50, 250, and 500mg/kg) through three time intervals (up to 7, 15, and 45days) on liver tissue was assessed. Hepatic catalase (CAT), glutathione (GSH), nitric oxide (NOx), and malondialdehyde (MDA) levels varied with the administered dose and exposure time of TiO2 NPs. As a result, TiO2 NPs caused a statistically significant decrease in hepatic CAT and GSH activities and a significant alleviation in MDA and NOx levels (p < 0.05), suggesting that the liver exposed to these various doses of TiO2 NPs suffered from severe oxidative stress. The extent of depletion of antioxidant enzymes and the elevation of MDA and NOx in the liver exposed to the highest dose and duration of TiO2 NPs 500mg for 45days was the greatest, suggesting that the toxicity might be dose and time dependent. Further, C-reactive protein (CRP) as an inflammatory marker was also alleviated, in addition to the apparent chromosomal aberration and liver pathologies including necrotic and fibrotic hepatocytes after exposure to 250 and 500mg/kg of TiO2 NPs for 14 and 45days that were deduced. Hence, nanotechnology-based industries are growing rapidly leading to large-scale production of engineered nanoparticles. They contribute to increased chances of human NPs exposure and health risk.

Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice.

Hepatotoxicity induced by acetaminophen (APAP)-overdose is a major concern in clinical practice. In the present work, the detoxifying effect of irbesartan (Irb) on the APAP-induced acute liver injury was evaluated in mice. Induction of acute liver injury in mice was established by a single intraperitoneal (IP) injection of APAP (0.5 g/kg), then mice were injected with Irb (50 or 75 mg/kg, IP), each given twice at 1 and 12 hours post APAP injection. Liver functions, hepatic oxidative and nitrosative stress markers, and liver histopathology were determined after 24 hours. Hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) levels were also estimated. Immunohistochemical evaluations of hepatic expression of phosphorylated NF-kB and active caspase-3 were assigned. Irb treatment attenuated APAP-induced acute liver injury. Irb suppressed APAP-caused elevation of liver enzymes as well as oxidative and nitrosative stress in liver tissues as evidenced by the decrease in hepatic CYP2E1 expression and hepatic levels of malondialdehyde and nitric oxide in addition to the elevated hepatic superoxide dismutase activity and reduced glutathione concentration. Also, Irb mitigated APAP-induced inflammation in liver tissues via decreasing the expression of hepatic NF-κB, phosphorylated NF-κB and TNF-α, and attenuated hepatic apoptosis via decreasing Bax/Bcl-2 ratio and caspase 3 expression and activation. Also, Irb mitigated the APAP-induced histopathological changes in liver specimens. These data suggested that Irb ameliorates APAP-induced acute liver injury through antioxidant, anti-inflammatory, and antiapoptotic activities.

Hepatoprotective effect of the unsaponifiable matter from olive, linseed and sesame oils against carbon tetrachloride-induced liver injury in rats

In the present study, the hepatoprotective activity of the unsaponifiable matter (UNSAP) of olive oil, linseed, and sesame oils against CCl4-induced liver toxicity in rats was investigated. In a preliminary antioxidant study, UNSAP showed pronounced DPPH radical scavenging activity (IC50 6.2-10.8 mg/mL). The constituents of UNSAP were determined by GC-MS. The subcutaneous administration of CCl4, caused liver injury. The hepatoprotective effect of UNSAP was comparable to that of α-tocopherol, a standard antioxidant agent. The co-administration of the investigated UNSAP normalized the activities of serum marker enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Furthermore, the serum alkaline phosphatase (ALP) activity and hepatic malondialdehyde (MDA) level were found to be alleviated by pre-treatment with the UNSAP. A histopathological evaluation showed marked improvement in the liver of UNSAP- and α-Tocopherol-treated animals. The hepatoprotective effect could be attributed to the antioxidant characteristics of UNSAP.

Upregulation of flavin-containing monooxygenase 3 mimics calorie restriction to retard liver aging by inducing autophagy.

Flavin-containing monooxygenase 3 (FMO3) gene expression is often upregulated in long-lived murine models. However, the specific relationship between FMO3 and aging remains unknown. Here, we show that 40% calorie restriction (CR), which is considered to be one of the most robust interventions to delay aging progression, markedly upregulates FMO3. Most importantly, upregulation of hepatocyte FMO3 in murine models prevented or reversed hepatic aging. Accordingly, the upregulation of FMO3 mimicked the effects of CR: reduced serum levels of pro-inflammatory cytokine interleukin-6 and fasting insulin; relief of oxidative stress, with lower hepatic malondialdehyde levels and higher superoxide dismutase activity; reduced serum and hepatic levels of total cholesterol and triglyceride, as well as reduced lipid deposition in the liver; and diminished levels of aging-related markers β-gal and p16. There were also synergistic effects between FMO3 upregulation and CR. Inhibition of autophagy blocked the anti-aging effects of upregulation of hepatocyte FMO3, including reversing the amelioration of the serum and hepatic parameters related to inflammation, oxidative stress, lipid metabolism, liver function, and hepatocyte senescence. Our results suggest that the upregulation of FMO3 mimics CR to prevent or reverse hepatic aging by promoting autophagy.

Physicochemical properties and hepatoprotective effects of glycated Snapper fish scale peptides conjugated with xylose via maillard reaction

The physicochemical properties and hepatoprotective effects of fish scales peptides (FSP) and the glycated peptides conjugated with xylose via Maillard reaction (FSP-MRPs) were investigated. Results showed that the FSP was rich in oligopeptides within 2–10 amino acids, the degree of grafting of FSP-MRPs was 52.97 ± 1.58% and the antioxidant activities in vitro of FSP were improved through Maillard reaction. In order to investigate the antioxidant activities of FSP-MRPs after digestion, the simulated gastrointestinal digestion experiments of FSP and FSP-MRPs in vitro were conducted. Results indicated that the antioxidant activities of FSP and FSP-MRPs remained as stronger as before even under the digestive conditions. Furthermore, FSP-MRPs could significantly reduce the elevated activities of serum aspartate aminotransferase and alanine aminotransferase, decrease the elevated the levels of hepatic malondialdehyde and triglyceride, and inhibit the decrease of hepatic superoxide dismutase, catalase and glutathione peroxidase caused by alcohol-induced liver damage. These findings suggest that the glycated peptides formed by FSP and xylose via Maillard reaction may be potential to be exploited as a potential functional ingredient in food industry.

Decreased malondialdehyde levels in fish (Astyanax altiparanae) exposed to diesel: Evidence of metabolism by aldehyde dehydrogenase in the liver and excretion in water.

Increased malondialdehyde (MDA) levels are commonly considered an indicator of lipid peroxidation derived from oxidative stress insults promoted by exposure of fish to pollutants. However, a decrease in MDA levels after xenobiotic exposure has been also reported, an effect that is mostly attributed to enhanced antioxidant defenses. In this study, we assessed whether pollutant-mediated MDA decrease would be associated with antioxidant enhancement or with its metabolism by aldehyde dehydrogenase (ALDH) in the liver and gills of lambari (Astyanax altiparanae) exposed to diesel oil (0.001, 0.01, and 0.1mL/L). MDA levels were decreased in the liver of lambari exposed to diesel. The activities of the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx), were unchanged in the liver, while that of glucose-6-phosphate dehydrogenase (G6PDH) was decreased. In contrast, levels of total glutathione (tGSH) and the activity of glutathione S-transferase (GST) were increased in the liver, which partly support antioxidant protection against lipid peroxidation. More importantly, ALDH activity increased in a concentration-dependent manner, being negatively correlated with MDA levels, indicating MDA metabolism by ALDH. In the gills, diesel exposure increased MDA and lipid hydroperoxide levels, and promoted increases in antioxidant defenses, indicating oxidative stress. Curiously, ALDH activity was undetectable in the gills, supporting the possibility of direct MDA excretion in the water by the gills. Analyses of MDA in the water revealed increased levels of MDA in the aquaria in which the fish were exposed to diesel, compared to control aquaria. A second experiment was carried out in which the fish were intraperitoneally injected with MDA (10mg/kg) and analyzed after 1, 6, and 12h. MDA injection caused a time-dependent decrease in hepatic MDA levels, did not alter ALDH, CAT, GPx, and GST activities, and decreased G6PDH activity and tGSH levels. In the gills, MDA injection caused a slight increase in MDA levels after 1h, but did not alter GPx, G6PDH, and GST activities. MDA injection also enhanced CAT activity and tGSH levels in the gills. MDA concentration in water increased progressively after 1, 6, and 12h, supporting the hypothesis of direct MDA excretion as an alternative route for MDA elimination in fish. Our results suggest that the decreased MDA levels after exposure of lambari to diesel oil pollutant probably reflects an association between enhanced antioxidant protection, MDA metabolism, and MDA excretion in water.

Syringic acid improves oxidative stress and mitochondrial biogenesis in the liver of streptozotocin-induced diabetic rats

Objective: To determine the effects of syringic acid on hepatic damage in diabetic rats.Methods: Diabetes was induced by streptozotocin. Diabetic rats were given syringic acid at doses of 25, 50 and 100 mg/kg by oral gavage for 6 weeks. Syringic acid effects on the liver were evaluated by examination of plasma biochemical parameters, and pathological study. In addition, biomarkers of lipid peroxidation and antioxidant status of liver tissues were assessed. Real time-PCR was performed to investigate the mRNA expression levels of mitochondrial biogenesis indices in different groups.Results: Syringic acid significantly attenuated the increase in most of plasma biochemical parameters in diabetic rats. Moreover, syringic acid treatment increased the catalase activity while it reduced the superoxide dismutase activity and hepatic malondialdehyde level in diabetic rats. There was no difference between the glutathione content of the treated and untreated groups. These findings were supported by alleviation of histopathological damages in the syringic acid-treated groups compared to the untreated diabetic group. Syringic acid also significantly up-regulated the hepatic mRNA expression of PGC-1a, NRF-1, and NRF-2 and increased the mtDNA/nDNA ratio in diabetic rats. Conclusions: Syringic acid can be considered as a suitable candidate against hepatic complications since it can reduce oxidative damages in diabetic cases. Furthermore, it has the potential of targeting hepatic mitochondria in diabetes.