Liver Glutathione Content Research Articles

Antioxidant capacity and hepatoprotective activity of myristic acid acylated derivative of phloridzin

The antioxidant activities in vitro and hepatoprotective effects against carbon tetrachloride (CCl4) induced acute liver injury in vivo of myristic acid acylated derivative of phloridzin (PZM) were investigated. The PZM was obtained by enzymatic acylation of myristic acid and phloridzin (PZ). The antioxidant capability of PZM in vitro was evaluated by the ferric reducing antioxidant power assay (FRAP), 2,2′-Azinobis- 3-ethylbenzthiazoline-6-sulphonate (ABTS+·) and 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging assay. Mice were intragastrically treated with control or PZM (20, 40, and 80 mg/kg) for 5 days and intra-peritoneal injection with CCl4. The enzymatic acylated synthesis of myristic acid and phloridzin was region-selective taken place on 6″-OH of phloridzin glycoside moiety and achieved 93% yield. PZM had a significantly higher total antioxidant ability, same scavenging ABTS+· ability and weaker scavenging DPPH· ability when compared to the parent PZ. The of aminotransferase serum activity and malondialdehyde hepatic activity were elevated (P < 0.015) after treatment with CCl4, while the related liver enzymatic activities and glutathione concentration were lower. These changes were enhanced by PZM. Further studies showed that PZM reduced the interleukin-6 expression and stimulated liver regeneration caused by CCl4. PZM attained good antioxidant capacity in vitro and had excellent hepatoprotective effects in vivo and better bioactivity compared to the parent phloridzin. The significance of hepatoprotective effect of phloridzin derivative against CCl4-induced hepatotoxicity in mice is an important and new finding.

Cytotoxic Effect of Propolis Nanoparticles on Ehrlich Ascites Carcinoma Bearing Mice

Background and objective Previous studies have demonstrated the anti-cancer effects of propolis. However, its use is limited because of its poor bioavailability. In the present study, the major objective was to improve propolis bioavailability using a nanosuspension formulation. The cytotoxic effect of propolis nanosuspension (PRO-NS) on the Ehrlich ascites carcinoma (EAC) in female Swiss albino mice was investigated in comparison to the free propolis. Materials and methods A propolis-loaded nanosuspension was formulated by applying solvent-antisolvent nano-precipitation technique. The prepared PRO-NS was characterized for average particle size, polydispersity index (PDI) and zeta potential. Also, the morphology of the nanosuspension particles was investigated using scanning electron microscopy (SEM). Moreover, PRO-NS cytotoxicity was tested using EAC bearing mice. The anticancer activity of Pro-NS was assessed by studying tumor volume, life span, viable and non-viable cell count, antioxidant, biochemical estimations and proliferation of EAC cells. Results The results revealed that propolis nanoparticles were relatively spherical in shape with rough surface. The tumor bearing mice treated with PRO-NS showed increased life span and inhibited tumor growth and the proliferation of EAC cells in comparison to the free propolis (p < 0.01). Moreover, Pro-NS ameliorated the increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, IgM and the level of creatinine and urea after implantation of EAC cells. In addition, PRO-NS improved the SOD activity and glutathione content of liver and EAC cells. Furthermore, PRO-NS inhibited the formation of lipid peroxidation products (MDA) and total IgG in EAC tumor bearing mice. Conclusions Our results indicate that PRO-NS has a strong inhibitory activity against growth of tumors in comparison to free propolis. The anti-tumor mechanism may be mediated by preventing oxidative damage, immune-stimulation and induction of apoptosis.

Analysis of factors affecting consumers’ intention to purchase organic vegetables in Ho Chi Minh City

Oxidative stress has been studied by scientists because it is a factor increasing diseases, such as cancer, diabetes... through the production of harmful free radicals to the body. Ganoderma lucidum (Curtis) P. Karst is always considered an important drug in the prevention and treatment of diseases by the action of polysaccharide and triterpenoid. In addition, Stevia rebaudiana Bertoni has recently been shown to have antioxidant and anti-inflammatory properties. Mint (Mentha avensis L.) is a common medicinal herb. The mixture consisting of the aqueous extract of Ganoderma lucidum (Curtis) P. Karst, mint and stevia powder had a high antioxidant activity, in free radical scavenging method (DPPH), reaching 85.7% at concentration 1000 μg/mL and valuable IC50 was 559.7 μg/mL. For in vivo study on the model of cyclophosphamide-induced liver damage in white mice, the concentrations of malondialdehyde and glutathione in liver showed that the mixture had antioxidant activity in the direction of hepatoprotective effect

Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway.

Toosendanin (TSN) is the main active compound in Toosendan Fructus and Meliae Cortex, two commonly used traditional Chinese medicines. TSN has been reported to induce hepatotoxicity, but its mechanism remains unclear. In this study, we demonstrated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in protecting against TSN-induced hepatotoxicity in mice and human normal liver L-02 cells. In mice, administration of TSN (10 mg/kg)-induced acute liver injury evidenced by increased serum alanine/aspartate aminotransferase (ALT/AST) and alkaline phosphatase (ALP) activities, and total bilirubin (TBiL) content as well as the histological changes. Furthermore, TSN markedly increased liver reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased liver glutathione (GSH) content and Nrf2 expression. In L-02 cells, TSN (2 μM) time-dependently reduced glutamate-cysteine ligase (GCL) activity and cellular expression of the catalytic/modify subunit of GCL (GCLC/GCLM). Moreover, TSN reduced cellular GSH content and the increased ROS formation, and time-dependently decreased Nrf2 expression and increased the expression of the Nrf2 inhibitor protein kelch-like ECH-associated protein-1 (Keap1). Pre-administration of quercetin (40, 80 mg/kg) effectively inhibited TSN-induced liver oxidative injury and reversed the decreased expression of Nrf2 and GCLC/GCLM in vivo and in vitro. In addition, the quercetin-provided protection against TSN-induced hepatotoxicity was diminished in Nrf2 knock-out mice. In conclusion, TSN decreases cellular GSH content by reducing Nrf2-mediated GCLC/GCLM expression via decreasing Nrf2 expression. Quercetin attenuates TSN-induced hepatotoxicity by inducing the Nrf2/GCL/GSH antioxidant signaling pathway. This study implies that inducing Nrf2 activation may be an effective strategy to prevent TSN-induced hepatotoxicity.

Bile acids regulate cysteine catabolism and glutathione regeneration to modulate hepatic sensitivity to oxidative injury.

Bile acids are signaling molecules that critically control hepatocellular function. Disrupted bile acid homeostasis may be implicated in the pathogenesis of chronic liver diseases. Glutathione is an important antioxidant that protects the liver against oxidative injury. Various forms of liver disease share the common characteristics of reduced cellular glutathione and elevated oxidative stress. This study reports a potentially novel physiological function of bile acids in regulating hepatic sulfur amino acid and glutathione metabolism. We found that bile acids strongly inhibited the cysteine dioxygenase type-1-mediated (CDO1-mediated) cysteine catabolic pathway via a farnesoid X receptor-dependent mechanism. Attenuating this bile acid repressive effect depleted the free cysteine pool and reduced the glutathione concentration in mouse liver. Upon acetaminophen challenge, cholestyramine-fed mice showed impaired hepatic glutathione regeneration capacity and markedly worsened liver injury, which was fully prevented by N-acetylcysteine administration. These effects were recapitulated in CDO1-overexpressing hepatocytes. Findings from this study support the importance of maintaining bile acid homeostasis under physiological and pathophysiological conditions, as altered hepatic bile acid signaling may negatively impact the antioxidant defense mechanism and sensitivity to oxidative injury. Furthermore, this finding provides a possible explanation for the reported mild hepatotoxicity associated with the clinical use of bile acid sequestrants in human patients.

Allablanckia floribunda hypotensive activity on ethanol induced hypertension in rats

Background: Chronic alcohol intake is related to hypertension. In the present work, we investigated the effect of Allablanckia floribunda Oliver (Clusiaceae) aqueous extract in alcohol-induced hypertensive rats and on related oxidative stress damages. Methods: Alcohol-induced hypertensive rats (AHR) was obtained by oral administration of ethanol (3 g/kg/day during 8 weeks). Blood pressure and heart rate were evaluated using the direct cannulation method. The effects of the extract on lipid profile as well as kidney and liver functions were studied. Free radical scavenging and antioxidant properties of the extract were evaluated by colorimetric method. The effects of A. floribunda were evaluated after 4 weeks of treatment with alcohol. Results: At the doses of 200 and 400 mg/kg/day, A. floribunda significantly decreased the mean blood pressure of AHR by 14.06 and 23.25 % respectively. Administration of the plant extract lead to the reduction of total cholesterol by 41.50% and 43.06%, HDL-cholesterol by 22.16 and 30.15% and artherogenic index by 69.78 and 74.43%, respectively at the doses of 200 and 400 mg/kg, as compared to untreated hypertensive rats. A. floribunda (200 and 400 mg/kg) decrease bilirubine (12.98 and 16.88%), urea (23.32% and 32.26 %), ALT (10.73 and 27.97%) and AST (29.80 and 42.22%) of treated AHR, respectively. The plant extract also reduced superoxide dismutase (SOD), malondialdehyde (MDA) and catalase and increased the reduced glutathione (GSH) concentration in aorta, heart, kidney and liver of AHR. Conclusion: These results suggest that the aqueous extract of A. floribunda possesses antioxidant and hypotensive activity in alcohol-induced hypertension.

Hepatoprotective effect of simvastatin in mice with DMBA-induced breast cancer: Histopathological, biochemical and antioxidant status evaluation

Introduction: This study evaluates the effects of simvastatin on the liver, in a mouse model of DMBA-induced breast cancer, with regards to histopathological, biochemical and antioxidant features.&#x0D; Methods: Mice were randomly divided into two groups: A (control group) and B (mammary tumor group); the latter group received DMBA (50 mg/kg) by oral gavage once a week for 4 consecutive weeks. Animals positive for breast cancer tumors were randomly divided into 3 subgroups: 1) no treatment group (D1), 2) mice that received simvastatin (80 mg/kg) per os (P.O.) daily for 4 consecutive weeks (D2), and 3) mice that received tamoxifen (50 mg/kg) P.O. daily for 4 consecutive weeks (D3).&#x0D; Results: Administration of simvastatin to D2 mice resulted in significantly higher superoxide dismutase (SOD) activity as well as glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC), and accompanied by reduced malondialdehyde (MDA) content in liver as compared to D1 group. Tamoxifen significantly increased liver glutathione (GSH) content as compared to D1 mice. Moreover, MDA levels in liver of mice treated with tamoxifen were significantly lower than in the D1 group. Mice in the D1 group showed significantly increased levels of alkaline phosphatase (ALP), aspartate transaminase (AST), and gamma-glutamyl transferase (GGT) in liver tissues; these levels were significantly reduced by simvastatin administration. Moreover, tamoxifen decreased ALP and AST activities. Histopathological examination of liver sections from mice in the D1 group showed severe deteriorative changes. The extent and severity of changes in D2 and D3 groups were almost the same and milder than D1 group.&#x0D; Conclusion: In conclusion, simvastatin appears to have a hepatoprotective role in mice with DMBA-induced breast cancer, due partly to its antioxidant properties.&#x0D;

Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats.

The aim of this study was to investigate the effect of ellagic acid (EA) on arsenic-induced renal and hepatic toxicity in rats. A total number of 35 male Wistar rats were randomly divided into five experimental groups. Group 1 received normal saline (po). Group 2 received sodium arsenite (SA, 10mg/kg, po) for 21days. Group 3 received EA (30mg/kg, po) for 14days. Groups 4 and 5 received SA 7days prior to EA (10 and 30mg/kg respectively) treatment and continued up to 21days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were measured in kidney and liver. Treatment with EA (more potently at dose of 30mg/kg) restored the SA-induced alterations in serum creatinine (Cr) and blood urine nitrogen (BUN) levels as well as the changes in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations (all p<0.001). Elevated levels of malondialdehyde (MDA) and nitric oxide (NO) in renal and hepatic tissue was reduced by EA treatment (all p<0.001). Treatment with EA enhanced the glutathione (GSH) content in liver (p<0.001) and up-regulated renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) mRNA expression (all p<0.001). The SA-induced histopathological alterations in kidney and liver were reduced by EA treatment. In conclusion, the presence of EA with SA alleviated its toxic effects and EA treatment might be an effective strategy for the management of arsenic-induced renal and hepatic damage.

Sub-lethal effects of herbicides penoxsulam, imazamox, fluridone and glyphosate on Delta Smelt (Hypomesus transpacificus)

Concerns regarding non-target toxicity of new herbicides used to control invasive aquatic weeds in the San Francisco Estuary led us to compare sub-lethal toxicity of four herbicides (penoxsulam, imazamox, fluridone, and glyphosate) on an endangered fish species Delta Smelt (Hypomesus transpacificus). We measured 17β-estradiol (E2) and glutathione (GSH) concentrations in liver, and acetylcholinesterase (AChE) activity in brain of female and male fish after 6 h of exposure to each of the four herbicides. Our results indicate that fluridone and glyphosate disrupted the E2 concentration and decreased glutathione concentration in liver, whereas penoxsulam, imazamox, and fluridone inhibited brain AChE activity. E2 concentrations were significantly increased in female and male fish exposed to 0.21 μM of fluridone and in male fish exposed to 0.46, 4.2, and 5300 μM of glyphosate. GSH concentrations decreased in males exposed to fluridone at 2.8 μM and higher, and glyphosate at 4.2 μM. AChE activity was significantly inhibited in both sexes exposed to penoxsulam, imazamox, and fluridone, and more pronounced inhibition was observed in females. The present study demonstrates the potential detrimental effects of these commonly used herbicides on Delta Smelt.

Effects of food restriction on the expression of genes related to acetaminophen-induced liver toxicity in rats.

It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the expression of drug-metabolizing enzyme genes and total glutathione content in the liver, which are related to toxicity induced by overdose of the hepatotoxic drug acetaminophen (N-acetyl-p-aminophenol; APAP), were examined in rats reared under different feeding conditions: ad libitum feeding, 16-h fasting, and food restriction (fed 70% of the average intake of ad libitum feeding for 10 days) conditions. The rats under food restriction conditions as well as fasted rats showed significantly higher expression of Cyp2e1, the gene encoding the enzyme that metabolizes APAP to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). They also had lower levels of liver total glutathione, which detoxifies NAPQI. In contrast, the gene expression of UDP-glucuronosyltransferase 1A6 (Ugt1a6), sulfotransferase 1A1 (Sult1a1), and glutathione S-transferase M1 (Gstm1) was not affected by food restriction or fasting. When APAP was administered (800 mg/kg), histopathological changes were not observed in rats fed ad libitum, while hepatocellular necrosis was observed in most of the rats treated with APAP after fasting or food restriction. Taken together, these results suggest that not only fasting but also food restriction exacerbate APAP-induced acute liver injury, probably by the induction of CYP2E1 and the reduction of liver glutathione contents, in rodents.

A proanthocyanidin-rich extract from Cassia abbreviata exhibits antioxidant and hepatoprotective activities in vivo

Ethnopharmacological relevanceCassia abbreviata is a small to medium sized branched umbrella-shaped deciduous tree. It is widely spread in the tropics, especially in Africa, having a long history in traditional medicine for the treatment of numerous conditions such as headaches, diarrhea, constipation, some skin diseases, malaria, syphilis, pneumonia, stomach troubles, uterine pains, and against gonorrhea. Aim of the studyWe investigated the phytochemical constituents of a root extract from Cassia abbreviata using HPLC-PDA-ESI-MS/MS. We also determined the antioxidant activities in vitro and in vivo using the nematode Caenorhabditis elegans as a model organism. The hepatoprotective activities in case of D-galactosamine (D-GaIN)-induced hepatotoxicity were studied in a rat model. Materials and methodsHPLC-PDA-ESI-MS/MS analysis allowed the identification of the secondary metabolites of the methanol extract. DPPH and FRAP assays were used to determine the antioxidant activities in vitro. Using the C. elegans model, survival rates under juglone induced oxidative stress, intracellular ROS content, quantification of Phsp-16.2: GFP expression and subcellular DAF-16: GFP localization were investigated to determine the antioxidant activities in vivo. The in vivo hepatoprotective potential of the root extract was evaluated for D-galactosamine (D-GaIN)-induced hepatotoxicity in rats. The activity of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), in addition to liver peroxidation product malondialdehyde (MDA) and glutathione content (GSH), as well as albumin and total bilirubin concentration, were determined. A histopathological study was also performed. Results and conclusionsC. abbreviata root extract is rich in polyphenolics, particularly proanthocyanidins. HPLC-PDA-ESI-MS/MS analysis resulted in the identification of 57 compounds on the bases of their mass spectra. (epi)-Catechin, (epi)-afzelechin, (epi)-guibourtinidol, and (ent)-cassiaflavan monomers as well as their dimers, trimers, and their diastereomers are the main components of the extract.The total phenolic content amounted for 474mg/g root extract expressed as gallic acid equivalent using the Folin-Ciocalteu method. The extract exhibited powerful antioxidant activity with EC50 of 6.3μg/mL in DPPH and 19.15mM FeSO4 equivalent/mg sample in FRAP assay. In C. elegans model, the extract (200μg/mL) was able to increase the survival rate by 44.56% and reduced the ROS level to 61.73%, compared to control group.Pretreatment of rats with 100mg extract/kg (b. wt.) reduced MDA by 47.36% and elevated GSH by 59.1%. The extract caused a significant reduction of ALT, AST and GGT activities by 11%, 35.7% and 65%, respectively.The findings of this study suggest that the proanthocyanidin-rich extract from C. abbreviata may be an interesting candidate for hepatoprotective activity in case of hepatocellular injury.

Effect of trace mineral source on mineral status and performance of beef steers fed low- or high-sulfur diets.

A 2 × 2 factorial assessed the effect of trace mineral (TM) sources fed within low- or high-S diets on the mineral status and performance of cattle. Angus crossbred steers ( = 48; 6/pen) were blocked by BW (316 ± 16.6 kg), assigned to low-S (0.27%; LS) or high-S (0.54%; HS; added as CaSO) diets, and supplemented TM at 10 mg Cu, 30 mg Zn, and 20 mg Mn/kg DM from hydroxy (HYD; IntelliBond; Micronutrients USA LLC, Indianapolis, IN) or inorganic (sulfates; ING) sources ( = 12 steers/treatment). Steers were fed corn silage and corn-based diets via GrowSafe bunks in the growing period (GP; 84 d) and finishing period (FP; 77 d), respectively. Plasma and liver were collected at trial initiation and end of GP and FP for mineral concentrations. End of GP and FP red blood cell lysate superoxide dismutase (SOD) and Mn-SOD activity and liver glutathione concentrations were measured. Data were used as a 2 × 2 factorial using Proc Mixed of SAS (SAS Inst. Inc., Cary, NC) with initial plasma and liver status analyzed as covariates. High S decreased ( < 0.01) liver Cu and tended ( ≤ 0.10) to decrease plasma Cu concentrations. Liver Cu concentrations were lower in HYD than ING in the FP ( < 0.01). High S decreased ( = 0.04) GP plasma Zn concentrations and tended to decrease ( = 0.10) GP liver Zn. There were GP ( = 0.05) and FP ( = 0.02) S × TM effects for liver Mn concentrations where GP LS-HYD was greater than all other treatments, whereas FP LS-HYD was lower than HS-HYD and LS-ING and FP HS-ING was less than LS-ING. Glutathione, SOD, and Mn-SOD were not different ( ≥ 0.13) in the GP, but S × TM tended to affect FP Mn-SOD ( = 0.10), where LS-HYD tended to be lower than LS-ING. Oxidized glutathione in FP tended to be lower ( = 0.06) for HYD than ING. In the GP, there were S × TM effects on performance where LS-HYD had greater ADG and G:F ( ≤ 0.05) than HS-HYD, whereas LS and HS-ING were intermediate. For FP performance S × TM effects were noted where LS-HYD and HS-ING tended ( = 0.10) to gain more than HS-HYD and HS-HYD had lower G:F ( = 0.04) than HS-ING. There were no effects of S × TM on final BW, DMI, or ADG ( ≥ 0.11); however, HS-HYD had lower G:F than other treatments overall ( = 0.05). High S decreased back fat and yield grade ( = 0.03), and rib eye area was smaller for HYD than ING ( = 0.02). In this study HS decreased markers of Cu and Zn status, and differential effects of HYD vs. ING minerals were noted across dietary phases, although all steers maintained adequate TM status.

The protective effect of Nigella Sativa oil extract against neurotoxicity induced by Valproic acid

Nigella sativa (NS), commonly known as black cumin, has been used for medicinal purposes. Traditionally the seeds and its oil are used in several diseases. The greatest part of the remedial properties of this plant is due to the presence of thymoquinone (TQ) which is a major active chemical component of the essential oil. The current study performed to evaluate the effect of Nigella sativa Oil (NSO) extract on the neurotoxic and hepatotoxic potentials from Valproic acid (VPA) administration. Also we summarize recent findings emphasizing the role of main neurotoxic and hepatotoxic markers and oxidative stress in study’s case. Neurotoxicity was induced by VPA at dose of (500 mg/kg b.wt) by gastric intubation daily for 30 day. These rats received NSO extract was given orally at dose of (0.5 ml/kg b.wt) daily for 30 days after VPA administration. The current results revealed that NSO extract treatment ameliorated significantly the elevated levels of the neurotoxic and hepatotoxic biomarkers which elevated as a result to VPA administration. Moreover, NSO extract treatment ameliorated the non-enzymatic antioxidant, brain and liver lipid peroxidation (LPO) and glutathione (GSH) concentration and the enzymatic antioxidant, brain and liver catalase(CAT) activity.

Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats.

Objective(s):Long term consumption of ethanol may induce damage to many organs. Ethanol induces its noxious effects through reactive oxygen species production, and lipid peroxidation and apoptosis induction in different tissues and cell types. Previous experiments have indicated the antioxidant characteristics of thymoquinone, the active constituent of Nigella sativa fixed oil, against biologically dangerous reactive oxygen species. This experiment was planned to evaluate the protective effect of thymoquinone against subchronic ethanol toxicity in rats.Materials and Methods:Experiments were performed on six groups. Each group consisted of six animals, including control group (saline, gavage), ethanol-receiving group (3 g/kg/day, gavage), thymoquinone (2.5, 5, 10 mg/Kg/day, intraperitoneally (IP)) plus ethanol and thymoquinone (10 mg/Kg/day, IP) groups. Treatments were carried out in four weeks.Results:Thymoquinone reduced the ethanol-induced increase in the lipid peroxidation and severity of histopathological alteration in liver and kidney tissues. In addition it improved the levels of proinflammatory cytokines in liver tissue. Furthermore, thymoquinone corrected the liver enzymes level including alanine transaminase, aspartate transaminase and alkaline phosphatase in serum and glutathione content in liver and kidney tissues. Other experiments such as Western blot analysis and quantitative real-time RT-PCR revealed that thymoquinone suppressed the expression of Bax/Bcl-2 ratio (both protein and mRNA level), and caspases activation pursuant to ethanol toxicity.Conclusion:This study indicates that thymoquinone may have preventive effects against ethanol toxicity in the liver and kidney tissue through reduction in lipid peroxidation and inflammation, and also interrupting apoptosis.

Hepatoprotective and hypoglycemic effects of a tannin rich extract from Ximenia americana var. caffra root

BackgroundLiver diseases and diabetes are serious health disorders associated with oxidative stress and ageing. Some plant polyphenols can lower the risk of these diseases. PurposeWe investigated the phytochemical profiling of a root extract from Ximenia americana var. caffra using HPLC-PDA-ESI-MS/MS. The antioxidant activities in vitro were investigated. The hepatoprotective activities were studied in rat models with d-galactosamine (d-GaIN)-induced hepatotoxicity and the antidiabetic activities in STZ-diabetic rats were also investigated. Materials and methodsHPLC-PDA-ESI-MS/MS was used to identify plant phenolics. The antioxidant activities in vitro were determined using DPPH and FRAP assays. The in vivo hepatoprotective activities were determined for d-GaIN-induced hepatotoxicity in rats. We determined the liver markers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), liver peroxidation product malondialdehyde (MDA), glutathione content (GSH), albumin and total bilirubin concentration. The histopathological changes in rat liver were also studied. The antidiabetic activities were also investigated in STZ-diabetic rats and serum glucose, serum insulin hormone, and lipid peroxides were determined. ResultsThe root extract is rich in tannins with 20 compounds including a series of stereoisomers of (epi)catechin, (epi)catechin-(epi)catechin, (epi)catechin-(epi)catechin-(epi)catechin, and their galloyl esters. Promising antioxidant potential was observed in vitro in DPPH assay with EC50 of 6.5 µg extract / 26 µg raw material and in FRAP assay with 19.54 mM FeSO4 compared with ascorbic acid (EC50 of 2.92 µg/ml) and quercetin (FeSO4 24.04 mM/mg), respectively. Significant reduction of serologic enzymatic markers and hepatic oxidative stress markers such as ALT, AST, MDA, GGT, and total bilirubin, as well as elevation of GSH and albumin were observed in rats with d-galactosamine-induced liver damage treated with the extract. These findings agree with a histopathological examination suggesting a hepatoprotective potential for the root extract. The root extract can mediate an antidiabetic effect by reducing elevated blood glucose and serum lipid peroxides levels and by increasing insulin in STZ-diabetic rats by −107, −31.1, +11.3%, respectively. ConclusionsThe results of this study suggest that the tannin-rich extract from Ximenia americana var. caffra could be an interesting candidate for the treatment of several health disorders associated with oxidative stress such as hepatocellular injury and diabetes.

The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats.

To investigate the protective effect of Thymus vulgaris (T. vulgaris) leaves 70% alcoholic extract against alcohol-mediate hepatotoxicity rats. The protective effect of T. vulgaris extract was investigated at dose of 500mg/kg/day (as 0.1 of LD50) orally against alcohol-mediate hepatotoxicity using adult male Wister albino rats during 21 days. Protective effect of T. vulgaris extract was evaluated comparing with silymarin standard drug at recommended dose (25mg/kg/day) orally for 21 days. Serum liver and kidney functions, serum lipid profile, liver antioxidant enzymes activities, liver glutathione concentration (GSH), liver oxidative parameters and histopathological study of liver and kidney were estimated to find out protective effect of T. vulgaris extract. Alcohol-mediate hepatotoxicity rats (alcohol-control) showed hepatocytes distortion represented as marked increment on liver biomarkers; alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) activities, as well as pronounced reduction on total protein and its fractions albumin and globulin production corresponding to normal ranges. Oxidative stress status was appeared on alcohol-control evident as significant depletion on GSH concentration, antioxidant enzymes activities; catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione- S- transferase (GST) and glutathione peroxidase (GPx) recorded significant dwindling, concurrence with significant augmentation on oxidative stress parameters; malondyaldehyde (MDA) and hydrogen peroxide (H2O2) concentrations with respect to normal values. Serum lipid profile was affected by alcohol administration, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were significantly reduced, meanwhile high density lipoprotein cholesterol (HDL-C) was raised comparing to normal ranges. Co-administration of T. vulgaris extract with alcohol showed protective effect on hepatocytes manifested as remarkable minimizing on ALP, AST and ALT activities and marked increment on total protein, albumin and globulin production compared to alcohol-control. Amelioration was achieved on oxidative stress status on rats co-administrated T. vulgaris extract with alcohol. Accordingly, antioxidant enzymes activities; CAT, SOD, GR, GST and GPx were significantly magnified, while oxidative stress parameters; MDA and H2O2 concentration were significantly lessened corresponding to alcohol-control. Also, lipid profile was markedly improved and risk ratio was lowered by T. vulgaris extract co-administrated in comparison with alcohol-control. All these obvious results were confirmed by histopathological examination, which illustrated that extract showed normalization of degenerated and fibrotic liver tissue as of alcohol-control. T. vulgaris extract protected hepatocytes from damaging by alcohol reflecting improvement on liver performance and inhibition of oxidative stress status of liver. T. vulgaris extract appeared hepatoprotective, hypolipidemic and antioxidant activities on alcohol-mediate hepatotoxicity rats compared to silymarin.

Metabolism of inhaled methylethylketone in rats

Methylethylketone (MEK) is widely used in industry, often in combination with other compounds. Although nontoxic, it can make other chemicals harmful. This study investigates the fate of MEK in rat blood, brain and urine as well as its hepatic metabolism following inhalation over 1 month (at 20, 200 or 1400 ppm). MEK did not significantly accumulate in the organism: blood concentrations were similar after six-hour or 1-month inhalation periods, and brain concentrations only increased slightly after 1 month’s exposure. Urinary excretion, based on the major metabolites, 2,3-butanediols (± and meso forms), accounted for less than 2.4% of the amount inhaled. 2-Butanol, 3-hydroxy-2-butanone and MEK itself were only detectable in urine in the highest concentration conditions investigated, when metabolic saturation occurred. Although MEK exposure did not alter the total cytochrome P450 concentration, it induced activation of both CYP1A2 and CYP2E1 enzymes. In addition, the liver glutathione concentration (reduced and oxidized forms) decreased, as did glutathione S-transferase (GST) activity (at exposure levels over 200 ppm). These metabolic data could be useful for pharmacokinetic model development and/or verification and suggest the ability of MEK to influence the metabolism (and potentiate the toxicity) of other substances.

Decrease of Pericytes is Associated With Liver Disease Caused by Ligature-Induced Periodontitis in Rats.

Damage caused by periodontitis not only affects periodontal tissues, but also increases the severity of various illnesses such as rheumatoid arthritis, diabetes, and liver diseases. The aim of this study is to investigate the association between induced periodontitis and damage caused through its systemic effects on the liver. Twenty rats were divided into two groups: control and periodontitis. The following parameters were evaluated: gingival bleeding index (GBI), probing depth (PD), myeloperoxidase (MPO) activity, alveolar bone loss (ABL) for periodontal tissues; histopathologic examination of gingival and liver tissues; immunohistochemistry to cells positive for neural/glial antigen 2 (NG2) expressed in hepatic pericytes, glutathione (GSH), and malondialdehyde (MDA) concentrations in liver; and serum levels of alanine aminotransferase and aspartate aminotransferase. GBI, PD, MPO, ABL, and histopathologic examinations demonstrated the development of periodontitis. There was a significant increase in microvesicular steatosis accompanied by a marked reduction in NG2+ pericytes in the periodontitis group compared with the control group. The periodontitis group had significantly lower GSH and higher MDA concentration in the liver compared with the control group. The present study results link the systemic effects of induced periodontitis with changes in hepatic tissues such as microvesicular steatosis, likely caused by an increase in oxidative stress and lipid peroxidation. The findings from the present study implicate an association between a decrease of pericytes and liver disease caused by ligature-induced periodontitis in rats.

Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail &amp;lt;i&amp;gt;Conus flavidus&amp;lt;/i&amp;gt; on &amp;lt;i&amp;gt;albino&amp;lt;/i&amp;gt; Mice

The genus <i>Conus</i> is equipped with a unique venomous mixture of conopeptides which secreted for predation and defense purposes. This work is aiming to explore and determine the effect of the crude venom of <i>Conus flavidus</i>, a worm-hunting cone snail inhabiting the Red Sea, on the oxidant/ antioxidant system in mice using some oxidative stress biomarker assays. In addition to assess its histopathological effects on some treated organs. The LC₅₀ were detected for the crude venom using the hemolytic assay (16.7 mg/ml) and male albino mice were injected intraperitoneally with ½ LC₅₀ (8.3 mg/kg B.Wt). Biochemically, after 2, 4, 6, 12, 24 hours of injection the results revealed significant inhibition of superoxide dismutase (SOD) and catalase (CAT) activities in blood and liver in almost all time intervals comparing with control one. However, it showed elevation in lipid peroxide content (LPC), protein carbonyl content (PCC), nitric oxide level (NO) reduced glutathione content (GSH) and total antioxidant capacity (TAC) contents of both blood and liver in almost all time intervals. Histopathologicaly, liver and heart were dissected after 1, 3 and 7 days of injection. The treated liver showed vacuolar degeneration, karyolosis and pyknosis, mild blood sinusoidal congestion and centrilobular necrosis. The treated heart illustrated degenerated myofibrils, pyknosis, edema, blood vessel congestion, loss of striation normal construction and fascicular pattern in the myocardium. These results revealed that <i>C. flavidus</i> crude venom has distinct effects upon the oxidant/antioxidant cellular system and degenerative pathological effects in some tissues of treated animals, proving that this venom may contain bioactive peptides, which could be purified and used for further pharmacological and drug discovery investigations in the future.

Effects of alpha-lipoic acid supplementation on growth performance, antioxidant capacity and biochemical parameters for ammonia-exposed broilers.

In order to estimate the effect of alpha-lipoic acid (LA) supplementation on relieving ammonia stress of broilers, 180 22-day-old male broilers were assigned to three groups, six replicates in each group and 10 birds per replicate. The three groups were: (1) a control group without ammonia stress; (2) exposure to 70ppm atmospheric ammonia (AM); (3) exposure to 70ppm atmospheric ammonia and administration of 300mg/kg LA (AM+LA). The experimental period was 3weeks. Results showed that average daily weight gain was increased and feed conversion ratio was decreased in the AM+LA group, compared with the AM group (P<0.05). Total superoxide dismutase and glutathione peroxidase activities in serum, and glutathione content in liver were higher in the AM+LA group than that in the AM group (P<0.05); however, serum malondialdehyde content was decreased by LA addition (P<0.05). Additionally, serum glutamic-pyruvic transaminase, creatine kinase and lactate dehydrogenase activities were reduced and albumin level was increased by LA addition (P<0.05). In conclusion, LA addition could relieve ammonia stress to restore broiler production performance to normal levels.