Hepatic Oxidative Stress Markers Research Articles

Genotoxicity of yellow shammah (smokeless tobacco) in murine bone marrow cells in vivo

Shammah is a traditional form of smokeless tobacco (ST) that is manufactured and used locally by people of Middle East with highest usage in Saudi Arabia, Yemen and Sudan. In Saudi Arabia, shammah comes in three variants: white, brown and yellow. In the present study, we investigated the genotoxicity of yellow shammah (YS) on bone marrow (BM) cells in vivo using mice. Bone marrow (BM) chromosomal aberration (CA) and micronucleus (MN) assay were performed and hepatic markers of oxidative stress were determined. Swiss albino mice were divided into five groups (n = 6) including negative control (NC) and positive control (PC) groups. The three treated groups included YS-100, 200 and 300 mg/kg, doses freshly prepared in 0.5% carboxymethyl cellulose (CMC) and administered orally once a day for 2 weeks. PC animals were administered cyclophosphamide (CP) at a dose of 40 mg/kg body weight, 24 h before termination. Two weeks continuous treatment of YS induced a dose dependent and significant increase in aberrant metaphases (AM), CA per cell and depression in mitotic activity. In micronucleus assay, YS treatment increased the percentage of micronucleated polychromatic erythrocytes (MNPCE) frequency and showed statistically significant reduction in polychromatic erythrocyte/normochromatic erythrocyte ratio at all doses, as compared to NC. YS also markedly inhibited the activities of superoxide dismutase, reduced glutathione and increased malondialdehyde content. CP was used as clastogen (positive control) and yielded the expected positive results. Therefore, it may be concluded that YS has genotoxic and cytotoxic effects for BM cells of mice in vivo.

Effect of Indigofera oblongifolia on the Hepatic Oxidative Status and Expression of Inflammatory and Apoptotic Genes during Blood-Stage Murine Malaria.

Malaria is a dangerous disease spread across several countries. Recent studies have focused on medicinal plants to discover alternative agents to the currently used drugs for malaria treatment. Here, we investigated the potential role of Indigofera oblongifolia leaf extract (IE) on hepatic inflammation in mice with Plasmodium chabaudi-infected erythrocytes. Female C57BL/6 mice were divided into three groups. The first group served as a control noninfected group, while the second and third groups were intraperitoneally injected with 106 erythrocytes parasitized by P. chabaudi. Mice from the third group were treated daily with a dose of 100 mg/kg of IE for 7 days. IE significantly reduced the number of leukocytes and apoptotic cells. The numbers of CD68-positive cells decreased in the livers of mice from the treatment group. Moreover, IE raised the hepatic antioxidant levels (glutathione and catalase) and reduced the levels of hepatic oxidative stress markers (malondialdehyde, nitric oxide, and reactive oxygen species). IE regulated some functions of the genes related to immune responses, including apoptotic genes (B-cell lymphoma-2, Bax, and caspase-3) and cytokine genes (interleukin-1β (IL-1β), IL-6, interferon-γ, and tumor necrosis factor-α). Therefore, IE exerts significant effects against malaria and protects the liver from injury caused by P. chabaudi via antioxidant and anti-inflammatory ways.

Effect of N-Acetyl cysteine and Pomegranate Peel Water Extract on Hepatotoxicity Induced by Paracetamol.

Background: One of the safest antipyretics, analgesics is paracetamol when used at therapeutic doses but overdoses caused hepatic necrosis. Recent researches were proven the ability of pomegranate to treat many diseases. For new ways to reduce paracetamol toxicity pomegranate peel extract was used in comparison to N- Acetyl cysteine a standard antidote for paracetamol toxicity. Methods: Seventy two adult male albino rats were divided equally into nine groups; Negative control group; Solvent )distilled water) group; N-Acetyl cysteine treated group (a single dose 150 mg/kg. B.w/day orally); Pomegranate peel extract treated group (a single dose 430mg/kg. b. W/ day orally); N-Acetyl cysteine and Pomegranate peel extract treated group (each rat was given same previous doses); Paracetamol group (a single dose of 400 mg/ kg. B.w / day orally); N-Acetyl cysteine; Pomegranate peel extract and combination of N-Acetyl cysteine and Pomegranate peel extract with paracetamol were three treatment groups received the same previous doses. Treatment Continued for 28 days. These samples were collected for matrix metalloproteinase assessment in blood serum; Hepatic antioxidants and Oxidative stress marker assessment in plasma and liver tissue homogenates and Routine liver injury marker assessment in blood serum. Res49ults: Treatment with paracetamol caused hepatic toxicity, the Pomegranate peel extract showed a mild hepatoprotective effect, N-acetyl cysteine showed the moderate hepatoprotective effect and combination treatment of N-Acetyl cysteine and Pomegranate peel extract showed the best hepatoprotective effect against paracetamol toxicity. Conclusion: Paracetamol is a hepatotoxic and combination of N-Acetyl cysteine and the Pomegranate peel extract is the best treatment against Paracetamol hepatic toxicity.

Hepatoprotective Activities of Ethanolic Roots Extract of Ageratum Conyzoides on Alloxan-Induced Hepatic Damage in Diabetic Wistar Rats

Introduction The aim of the present study was to evaluate the hepatoprotective activities of the ethanolic roots extract of Ageratum conyzoides (AC) in alloxan-induced hepatic damage in diabetic rats. Materials and Methods Diabetes was induced in Wistar rats by the administration of alloxan (150 mg/kg, intraperitoneal). The ethanolic roots extract of AC, at doses of 250 and 500 mg/kg of body weight, was administered to diabetes-induced rats at a single dose per day for a period of 28 days. Results The effect of the ethanolic roots extract of AC on blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic oxidative stress markers was measured in the diabetic rats. The ethanolic roots extract of AC exhibited significant reduction of blood glucose (p < 0.05) at the dose of 500 mg/kg when compared with the standard drug glibenclamide (600 µg/kg). The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased significantly (p < 0.05) in the diabetic group without treatment when compared with the control group. In addition, the levels of oxidative stress markers, such as superoxide dismutase (SOD), catalase (CT), glutathione peroxidase (GPx), and glutathione (GSH), were significantly decreased in the diabetic rats compared with the normal rats, while the lipid peroxidation significantly increased in the diabetic group without treatment compared with the control (normal) group. The results demonstrated that the morphological, functional and oxidative stress changes in the liver caused by the ingestion of alloxan were attenuated in diabetic rats treated with the ethanolic roots extract of AC. Conclusion We concluded that the ethanolic roots extract of AC possesses significant antidiabetic, antioxidant and hepatoprotective effects on alloxan-induced diabetic rats.

Sub-chronic oral toxicity assessment (90 days) of ethanolic fraction of leaves of Neurocalyx calycinus (R. Br. ex Benn.) Rob. in rodents: A lesser known ethnomedicinal plant from the Cholanaickan tribal community, India.

The objective of the present study was to evaluate the safety of long term consumption of ethanolic fraction of Neurocalyx calycinus leaves (NCEF) in rodents. The NCEF was subjected to detect the presence of various phytoconstituents. In acute oral toxicity study, graded doses of NCEF was administered in mice and were observed up to 14 days. In sub-chronic oral toxicity study, NCEF was administered to Wistar rats at doses of 50, 500 and 1000 mg/kg b.w. per day for 90 days and after that, observed up to 28 days. NCEF showed the presence of alkaloids, steroids, phenolics and glycosides. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the highest dose level (6400 mg/kg b.w.). In sub-chronic oral toxicity study, there were no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical, hepatic oxidative stress marker analysis and urine analysis revealed the non-adverse effects of prolonged oral consumption of NCEF. The histopathologic examination did not show any differences in vital organs. Based on our findings, NCEF, at dosage levels up to 1000 mg/kg b.w., is non-toxic and safe for long term oral consumption.

Ablation of carotenoid cleavage enzymes (BCO1 and BCO2) induced hepatic steatosis by altering the farnesoid X receptor/miR-34a/sirtuin 1 pathway

β-Carotene-15, 15′-oxygenase (BCO1) and β-carotene-9′, 10′-oxygenase (BCO2) are essential enzymes in carotenoid metabolism. While BCO1/BCO2 polymorphisms have been associated with alterations to human and animal carotenoid levels, experimental studies have suggested that BCO1 and BCO2 may have specific physiological functions beyond the cleavage of carotenoids. In the present study, we investigated the effect of ablation of both BCO1/BCO2 in the development of non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism(s). BCO1/BCO2 double knock out (DKO) mice developed hepatic steatosis (8/8) and had significantly higher levels of hepatic and plasma triglyceride and total cholesterol compared to WT (0/8). Hepatic changes in the BCO1/BCO2 DKO mice were associated with significant: 1) increases in lipogenesis markers, and decreases in fatty acid β-oxidation markers; 2) upregulation of cholesterol metabolism markers; 3) alterations to microRNAs related to TG accumulation and cholesterol metabolism; 4) increases in an hepatic oxidative stress marker (HO-1) but decreases in anti-oxidant enzymes; and 5) decreases in farnesoid X receptor (FXR), small heterodimer partner (SHP), and sirtuin 1 (SIRT1). The present study provided novel experimental evidence that BCO1 and BCO2 could play a significant role in maintaining normal hepatic lipid and cholesterol homeostasis, potentially through the regulation of the FXR/miR-34a/SIRT1 pathway.

Evaluation of hepatoprotective activity of Syringa oblata leaves ethanol extract with the indicator of glutathione S-transferase A1

The leaves of Syringa oblata Lindl., Oleaceae, had been extensively used as a folk medicine to treat various infections, heal inflammations, icteric hepatitis and acute mastitis. The study was designed to evaluate the hepatoprotective activity of S. oblata leaves ethanol extract against CCl4-induced hepatotoxicity in primary hepatocytes and mice with the indicator of glutathione S-transferase alpha 1. The hepatoprotective effects of S. oblata leaves ethanol extract were evaluated on the basis of liver histopathology and biochemical parameters as well as hepatic oxidative stress markers. The results showed that CCl4 negatively modulated biochemical parameters and liver antioxidant activities. However, the use of S. oblata leaves ethanol extract restored altered-serum biochemical parameters and liver antioxidant activities in a dose-dependent manner. Importantly, the trends in S-transferase alpha 1 were similar to alanine aminotransferase and aspartate aminotransferase level, and S-transferase alpha 1 was suggested to be a marker for the evaluation of hepatoprotective activity of S. oblata leaves ethanol extract. Histopathological examination showed that CCl4 causes significant hepatic injury relative to control group. The above findings suggested that S. oblata leaves ethanol extract has hepatoprotective effects against CCl4-induced hepatic injury and S-transferase alpha 1 may be an indicator to evaluate the protective effects of S. oblata leaves ethanol extract.

Effects of maternal serine supplementation on high-fat diet-induced oxidative stress and epigenetic changes in promoters of glutathione synthesis-related genes in offspring

To elucidate the effects of maternal serine supplementation during pregnancy on high-fat (HF) diet-induced oxidative stress in the offspring and the epigenetic mechanisms involved, a control diet, HF diet, or HF diet supplemented with different concentrations of serine dissolved in water was fed to C57BL/6J mouse dams during gestation. Eight male offspring from each dietary group were sacrificed at weaning, Consequently, the serum and hepatic oxidative stress markers and lipid levels in weanlings from dams fed the HF diet supplemented with 1% serine were lower than those of offspring from dams fed the HF diet. Maternal serine supplementation prevented promoter DNA hypermethylation of HF diet-induced glutathione synthesis-related genes, and increased the gene expression and resultant protein contents in the weanlings. Our results therefore suggest that maternal serine supplementation during pregnancy alleviates HF diet-induced oxidative stress by epigenetically regulating glutathione synthesis in the weanling.

Pinelliae Rhizoma Praeparatum Involved in the Regulation of Bile Acids Metabolism in Hepatic Injury

Pinelliae Rhizoma Praeparatum (PRP) as traditional Chinese medicine had been used for hepatic diseases in combinative forms. However, the effect of PRP was not clear when used alone. So to explore the hepatoprotective/hepatotoxin of PRP is necessary. The activities of PRP were investigated in acetaminophen-induced hepatic injury mice. Liver function markers, hepatic oxidative stress markers were evaluated. Bile acids metabolic transports and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected. As a drug for the treatment of liver diseases, PRP slightly restored the parameters towards normal in model mice only in low dosage, and also had no antioxidant activity and regulate Nrf2. Cholestasis was significantly elevated in model mice when pretreatment with routine or high dosage of PRP, but had no effect on normal mice. Bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) in model mice were markedly increased when pretreatment with low dose PRP, but significantly decreased when pretreatment in routine or high dosage. Mrp3 was significantly induced in model mice after pretreatment of PRP. But the adjustment effect to bile acids transporters by PRP was not significant in normal mice. These results reveal that PRP has the different effects on bile acids transporter in hepatic injury mice, and therefore, the dosage of PRP need to be paid attention to when it is used in clinical hepatic injury.

Different administration patterns of docosahexaenoic acid in combating cytotoxic manifestations due to arsenic trioxide (acute promyelocytic leukemia drug) induced redox imbalance in hepatocytes

Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2O3), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/combination/post-administration patterns against As2O3 induced toxicity. The therapeutic concentration of As2O3 (10 μM) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group. Reduced cell viability, morphological alterations, enhanced LDH release and apoptosis were observed. The oxidative stress markers (lipid peroxidation, nitric oxide, and ROS) and hepatic enzymes (AST and ALT) and intracellular calcium levels were found to be elevated by the As2O3 administration. Reduction in levels of mitochondrial membrane potential, cellular free radical scavenging potential, intracellular proteins, ATPases and major antioxidants (catalase, SOD, GSH, and GPx) were also observed. Administration of DHA along with As2O3 as pre/combination administration patterns offered protection against As2O3 induced cytotoxicity at significant levels (p < 0.05) from As2O3 alone treated group. The cell viability and morphology were protected with reduced LDH release and apoptosis. The hepatic enzymes and oxidative stress markers were reduced with replenishment of mitochondrial membrane potential, free radical scavenging potential, intracellular proteins, ATPases and antioxidant levels. DHA pre/combination administration patterns showed protective potential against As2O3 with pre-treatment being the best and the post-treatment method failed to produce any protective effect.

Chemosensitizing effect of Alpinia officinarum rhizome extract in cisplatin-treated rats with hepatocellular carcinoma

This study was conducted to estimate the preventing and sensitizing efficiency of Alpinia officinarum rhizome extract (AORE) in an experimental model of hepatocellular carcinoma (HCC) +/− cisplatin. HCC was induced by a single intraperitoneal (i.p) dose of diethylnitrosamine (DENA, 200mg/kg). After 14 days, phenobarbitone (PB, 0.05%) was added to drinking water for 14 weeks to promote hepatocarcinogenesis. Cisplatin (CP) was given in a dose of 1.5 mg/kg (i.p), twice a week, alone or with AORE (400 mg/kg daily, orally) for 21 days. AORE was tried as a protective before the induction of HCC for three weeks as well. Results revealed that DENA/PB elevated hepatic indices as ALT and AST and total bilirubin with declining serum total protein. It increased oxidative stress, as hepatic malondialdehyde (MDA) with depressed hepatic reduced glutathione (GSH) contents, superoxide dismutase (SOD) and catalase activities. This was accompanied by an increase in hepatic expression of antioxidant genes (thioredoxin and glutaredoxin). Hepatocarcinogenesis was detected by histopathological changes in liver sections and the elevation of serum alpha-fetoprotein (AFP) level. Treatment with CP partially restored altered hepatic functions and oxidative stress markers. It also showed a partial decrease in the expression of antioxidant genes, improving histopathological changes in the liver and AFP level in serum. The treatment with AORE alone or AORE+CP enhanced hepatic function and oxidative stress markers. It also caused a decrease in the expression of antioxidant genes and improved histopathological changes in liver and serum AFP level. This effect is more potent than the treatment with CP alone. Our study suggested that AORE can be used as a promising natural chemoprevention or a chemosensitizing agent against hepatocarcinogenesis.

Role of nitric oxide and KATP channel in the protective effect mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats

Liver fibrosis is one of the most serious conditions affecting patients worldwide. In the present study, the role of nitric oxide and KATP channel was investigated for the first time in the possible protection mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats. Nicorandil (3 mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed marked improvement in liver function tests, hepatic oxidative stress and inflammatory markers as well as inducible and endothelial nitric oxide synthase protein expressions. Furthermore, nicorandil administration led to significant decrement of phosphorylated protein kinase C, fibrosis and hepatic stellate cells activation as indicated by decreased alpha smooth muscle actin expression. Oral co-administration of glibenclamide (5 mg/kg/day) (a KATP channel blocker) with nicorandil mostly showed similar improvement though not reaching to that of nicorandil group. However, co-adminstration of L-NAME (15 mg/kg/day) (an inhibitor of nitric oxide synthase) completely abolished the protective effects of nicorandil and produced more or less similar results to that of untreated bile duct ligated group. In conclusion, nicorandil is an effective therapy against the development of bile duct ligation-induced liver fibrosis in rats where nitric oxide plays a more prominent role in the protective effect of nicorandil than KATP channel opening.

Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide

BackgroundCyclophosphamide (CP) is an anticancer drug utilized for treatment of many types of cancer. CP causes many side effects such as hepatotoxicity and mutagenicity. Garlic has long been used as a spice and food additive and is considered as one of the important medicinal plants. Garlic had medicinal importance as it has hepatoprotective, antimicrobial, antioxidant, anti-inflammatory, antithrombotic, antihypertensive, and antihyperlipidemic properties. The purpose of the presented study is to investigate the protective role of aged black garlic against cyclophosphamide-induced hepatotoxicity and apoptosis. The present work was carried out by routine histological H&E stain, histochemical Feulgen stain for DNA, immunohistochemical stain Bcl-2 as apoptotic marker, comet assay, serum biochemical analysis for liver function markers (ALT, AST, albumin, and bilirubin), and hepatic oxidative stress markers (MDA, CAT, SOD, and GPx).ResultsCyclophosphamide induced histological alteration as fatty degeneration, blood venous congestion, pyknosis, necrosis, and vaculations. CP caused a decrease of DNA content, an increase of Bcl-2 immunoreactivity, and increase of DNA damage. Biochemical investigations showed that CP induced significant elevation of ALT, AST, bilirubin, and hepatic MDA. Moreover, CP induced reduction of albumin and hepatic SOD, CAT, and GPx values. Aged black garlic induced significant improvement of alterations induced by CP, when compared with CP-treated group.ConclusionAged black garlic succeeded in protecting the liver from apoptosis and pathological alterations induced by CP.

Evaluation of the effects of TAK-242 and GIT-27 on methotrexate-induced liver injury

Background: Methotrexate (MTX)-induced liver injury is a common problem that is described as increased level of hepatic biomarkers that is seen in 14%–25% of patients with inflammatory bowel disease and 49% of patients with rheumatoid arthritis or as idiosyncratic induced liver injury that is seen in 1% of patients with inflammatory bowel disease, or as fibrosis and cirrhosis in 17% of rheumatoid arthritis patients and 25% of psoriatic patients. This profile may rarely progress to acute liver failure. Aim: The aim is to study the effect of TAK-242 and GIT-27 on MTX-induced liver injury. Materials and Methods: Thirty-five Albino-Wistar rats were divided into five groups: the first group was maintained on distilled water, the second group was administered intraperitoneal (I.P.) dimethyl sulfoxide followed by oral MTX, the third group was administered oral MTX, the fourth group was administered I.P. TAK-242 followed by oral MTX, and the fifth group was administered I.P. GIT-27 followed by oral MTX. Results: The significant increase in markers of hepatic function, inflammatory and oxidative stress markers, as well as severe liver histopathologic change “steatosis” induced by methotrexate were alleviated in the animals pretreated with the drugs TAK-242 and GIT-27. With significant improvement in serum level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, interleukin-6, tumor necrosis factor-α, malondialdehyde and reduced glutathione; beside an improved histopathologic profile of moderate steatosis. Conclusion: This study suggests that both TAK-242 and GIT-27 protect against liver injury induced by MTX depending on their antagonism of the inflammatory Toll-like receptors 4 and 2/6.

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.

Terminalia bellirica (Gaertn.) Roxb. fruit mitigates CCl4 induced oxidative stress and hepatotoxicity in rats

Terminalia bellirica (Gaertn.) Roxb. is a medicinal plant used for the treatment of various ailments in the traditional system of medicine like Ayurveda where it has been prescribed as a rejuvenator and general health tonic. The fruit of the plant is one of the components of the age old ayurvedic formulation-‘Triphala’. The present study evaluates curative effect of aqueous acetone extract of Terminalia bellirica fruits (AATB) against CCl4 induced oxidative stress and liver damage in an animal model. Two doses of the fruit extract (200mg/kg body weight and 400mg/kg body weight) were investigated for the beneficial effects. At the end of the treatment, liver function markers (ALT, AST, ALP, GGT, LDH, total bilirubin, total protein, albumin, globulin, albumin-globulin ratio) as well as hepatic oxidative stress markers (SOD, CAT, GSH) were evaluated. Treatment with AATB significantly restored the parameters towards normal level as compared to the elevated biochemical markers in the CCl4 treated animals. Reversal to normal tissue architecture was observed in histological evaluation. The results of AATB (400mg/kg) were found comparable with that of standard drug silymarin in all the parameters. The above findings suggest the therapeutic potential of the plant in alleviating hepatic oxidative stress and tissue damage, hence the traditional use of the plant in this regard stands justified.

Spirulina Protects against Hepatic Inflammation in Aging: An Effect Related to the Modulation of the Gut Microbiota?

Aging predisposes to hepatic dysfunction and inflammation that can contribute to the development of non-alcoholic fatty liver disease. Spirulina, a cyanobacterium used as a food additive or food supplement, has been shown to impact immune function. We have tested the potential hepatoprotective effect of a Spirulina in aged mice and to determine whether these effects can be related to a modulation of the gut microbiota. Old mice have been fed a standard diet supplemented with or without 5% Spirulina for six weeks. Among several changes of gut microbiota composition, an increase in Roseburia and Lactobacillus proportions occurs upon Spirulina treatment. Interestingly, parameters related to the innate immunity are upregulated in the small intestine of Spirulina-treated mice. Furthermore, the supplementation with Spirulina reduces several hepatic inflammatory and oxidative stress markers that are upregulated in old mice versus young mice. We conclude that the oral administration of a Spirulina is able to modulate the gut microbiota and to activate the immune system in the gut, a mechanism that may be involved in the improvement of the hepatic inflammation in aged mice. Those data open the way to new therapeutic tools in the management of immune alterations in aging, based on gut microbe-host interactions.

Hepatoprotective effect of blocking N-methyl-d-aspartate receptors in male albino rats exposed to acute and repeated restraint stress.

Stress affects many organs in addition to the brain, including the liver. We assessed the effects on the liver of blocking N-methyl-d-aspartate (NMDA) glutamate receptors with memantine in acute and repeated restraint stress. Forty-two male albino rats were divided into 7 groups; control, acute restraint stress (ARS), ARS + memantine, repeated restraint stress, repeated restraint + memantine, and positive control groups. We measured serum iron, zinc, alanine transferase and aspartame transferase, hepatic malondialdehyde, tumor necrosis factor-α (TNF-α), glutathione peroxidase, superoxide dismutase, metallothionein content, zinc transporter ZRT/IRT-like protein 14 mRNA expression, and hepcidin expression. We conducted a histopathological evaluation via histological staining and immunostaining for glial fibrillary acidic protein and synaptophysin expression, both of which are markers of hepatic stellate cell (HSC) activation. Both ARS and repeated stress increased markers of hepatic cell injury, oxidative stress, and HSC activation. Blocking NMDA with memantine provided a hepatoprotective effect in acute and repeated restraint stress and decreased hepatic cell injury, oxidative stress, and HSC activation.

Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.

Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF). We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000. In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P=0.023 and P=0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (≤1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P=0.007 and P=0.037, respectively). Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.

Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure.

Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1mg/kg bw of LTC for 7, 30, 45, and 60days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as potential biomarker in human biomonitoring studies.