Induced Liver Oxidative Damage Research Articles

Antioxidative and anti-inflammatory effects of vitamin C on the liver of laying hens under chronic heat stress.

In this study, we investigated the therapeutic effect and mechanism of action of vitamin C on chronic heat stress (CHS)-induced liver oxidative damage and inflammation in laying hens. The thermoneutral control group (TN group) was kept at a constant temperature of 22 ± 1°C, while the chronic heat stress group (CHS group) and the vitamin C supplemented group (HSV group) were exposed to heat stress (HS) (36 ± 1°C, 8 h/d). The TN and HS groups were fed the basic diet at will, and the HSV group was supplemented with 300 mg/kg of vitamin C on top of the basic diet. The experimental results showed a significant improvement in body weight and feed intake in the HSV group compared to the HS group. A significantly lower pH and higher and PCO2 levels were observed in the HSV group compared to the CHS group. As laying hens were supplemented with vitamin C, serum malondialdehyde (MDA) level was declined, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased, and total antioxidant capacity (T-AOC) was increased. Further, CHS induced an increase in the expression of inflammation-related genes and a decrease in the expression of antioxidant-related genes. In contrast, the addition of vitamin C reversed the effects of CHS, resulting in an increase in the expression of antioxidant-related genes and a decrease in the expression of inflammation-related genes. In conclusion, vitamin C can effectively alleviate CHS-induced acid-base imbalance in body fluids of laying hens and the oxidative damage and inflammatory response caused to the liver. Therefore, vitamin C can be used clinically as an effective drug to alleviate chronic heat stress in laying hens. This experiment provides clinical evidence and theoretical basis for the use of vitamin C as an effective drug to alleviate chronic heat stress in laying hens.

The antioxidant study proprieties of Thymus munbyanus aqueous extract and its beneficial effect on 2, 4-Dichlorophenoxyacetic acid -induced hepatic oxidative stress in albino Wistar rats

Herein, we investigated the antioxidant and hepatoprotective effects of thyme (Thymus munbyanus: AETM) on 2,4-dichlorophenoxyacetic acid (2,4 -D) - induced liver oxidative damage in rats. The phytochemical study of AETM revealed potent antioxidant properties owed to its richness in phenolic compounds including flavonoids, tannins, and phenolic acids. Further, in vivo animal study was conducted on 24 Wistar rats divided equally into control group and three treated groups, receiving orally AETM (10 ml/kg body weight (b.w), 2,4-D (5 mg/kg (b.w) and AETM + 2,4 – D (combined treatment) for 30 consecutive days. The results showed a significant increase in the enzymatic activity of transaminases (AST, ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (γ-GT), lactate dehydrogenase (LDH), and the levels of malondialdehyde (MDA) and carbonyl proteins (CPO), along with a significant decrease in plasma total protein, albumin, hepatic glutathione (GSH) contents, and the enzymatic activity of the hepatic antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione- S- transferase (GST)) in 2,4- D treatment compared with control. Moreover, no significant changes in these parameters were noticed in AETM treated animals as compared to control, and hence the combined treatment (AETM + 2,4- D) showed a marked enhancement in the above altered hepatic functional and antioxidant parameters and liver histopathology. In conclusion, AETM, owing to its richness with phenolic compounds proved to be an efficient antioxidant against 2,4-D - induced liver oxidative damage, and hence complementary studies would be needed to appear the use of these compounds as supplements in treating liver impairment.

Millettia aboensis ameliorates oxidative stress through synergic interaction of its active compounds.

Background M. aboensis has wide ethnopharmacological applications but very little has been done on the pharmacological basis for these indications. This study evaluated the antioxidant potentials of the leaf extracts of M. aboensis. Methods Total phenolic content of the extract and fractions was carried out using folin-ciocalteu method while in vivo site specific effect determined using carbon tetrachloride (CCl4)-induced liver oxidative damage. Chromatographic separations of the most active fraction led to the isolation of compounds 1 and 2 with their structures elucidated by a combination of 1D and 2D NMR and mass spectrometry. Inhibition of liver microsome lipid peroxidation was used to evaluate the antioxidant activities of these compounds while DPPH test was used to study their interaction. Results Ethyl acetate fraction had the highest phenolic content of 305.2mgGAE/g with n-hexane fraction having the least (26.1mgGAE/g). Structural elucidation revealed compound 1 as epicathechin-(2β→O→7, 4β→8)-cathechin and compound 2 as epicathechin-(2β→O→7, 4β→8)-epicathechin. Compounds 1 & 2 inhibited liver microsome lipid peroxidation with EC50 of 46 and 55 µg/mL respectively. Combination of the compounds produced synergic inhibition of DPPH radical with EC50 of 7 µg/mL against 9 µg/mL produced by ascorbic acid. Conclusion M. aboensis expressed strong antioxidant property which may explain its diverse ethnopharmacological uses.

Effect of lentivirus-mediated shRNA targeting down-regulation of PPARα on perfluorododecanoic acid induced oxidative damage in rat hepatocytes BRL 3A

To investigate the role of peroxisome proliferator-activated receptor alpha(PPARα) in perfluorododecanoic acid(PFDoA)-induced liver oxidative damage in rats by observing lentivirus-mediated shRNA targeting and down-regulating PPARα expression in rat hepatocytes BRL 3 A. A PPARα lentivirus-compatible shRNA interference vector Lenti-iPα and a negative control vector Lenti-NC were constructed, and co-transfected with lentivirus packaging helper plasmids into 293 FT cells for lentivirus packaging. The lentivirus stock solution was collected, concentrated and the virus titer was determined. The experimental grouping was as follows, NC-group(infected with negative control lentivirus, without PFDoA exposure), NC+ group(infected with negative control lentivirus, 75 μmol/L PFDoA exposure), iPα-group(infected with interference lentivirus, without PFDoA exposure), iPα+ group(infected with interference lentivirus, 75 μmol/L PFDoA exposure). Rat hepatocytes BRL 3 A cells were treated with lentivirus for 96 h, and then exposed with 75 μmol/L PFDoA in the NC+ group and iPα+ group in the last 24 h. The interference of PPARα in BRL 3 A cells and the role of PPARα in reactive oxygen species(ROS) changes caused by PFDoA were observed. Lentivirus-mediated shRNA successfully achieved targeted downregulation of PPARα expression in BRL 3 A cells. Compared with the NC-group, the mean fluorescence intensity of ROS in rat hepatocytes BRL 3 A in the iPα-group was 12043. 42±808. 58, significantly increased(P<0. 05); The transcription levels of acyl-CoA thioesterases(Acot) 1 gene and its protein expression levels were 0. 43±0. 04 and 0. 34±0. 08, respectively, both significantly decreased(P<0. 05). After PFDoA treatment, compared with NC+ group, the mean fluorescence intensity of ROS in iPα+ group was 12386. 25±356. 36, which also increased significantly(P<0. 05). The transcription levels of Acot1 gene and its protein expression levels were 0. 85±0. 10 and 0. 33±0. 04, respectively, which also decreased significantly(P<0. 05). PPARα and its downstream target protein Acot1 may play a role in scavenging ROS in rat hepatocytes BRL 3 A, keeping hepatocytes from oxidative damage caused by foreign substances to the liver.

Amelioration of Rifampicin and Isoniazid Induced Liver Oxidative Damage and Inflammation Response by Propolis Extracts in Rodent Model

Liver diseases pose a serious threat to human health and the conventional drugs available for the treatment of this life threatening condition often causes inadequate results. Propolis has been used from centuries traditionally for their hepatoprotective effect. We wanted to assess the liver protective activity of Propolis. The aim of the present study was to investigate the liver protective effect of hydro-alcoholic & aqueous extracts of Propolis against isoniazid and rifampicin (INH-RIF) induced oxidative damage and inflammation response in Wistar rats. Two different extracts, hydro-alcoholic (KPHa) & aqueous (KPAq) extracts of Propolis (400 mg/kg b.wt. p.o.) were administered orally daily for 14 days to INH-RIF induced rats. The liver protective effect was assessed by hepatic enzyme markers, in-vivo antioxidant, histopathological and immunohistochemistry studies. The study group was compared with the control group by one-way ANOVA, followed by Bonferoni’s test. A p-value of <0.01 was considered significant. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg each) intraperitoneal (i.p.) injection for 14 days. Administration of both, KPHa & KPAq, extracts at a dose of 400 mg/kg b.wt, p.o markedly controlled all modulating oxidative, hepatic damage markers and resulted in a significant decrease of INH-RIF induced damage in liver. Our current study demonstrate that the KPHa & KPAq extracts (from Kashmir propolis) were liver protective agents against INH-RIF induced hepatic injury.

Effect of IL-18 binding protein on hepatic ischemia-reperfusion injury induced by infrarenal aortic occlusion.

PurposeSevere local and systemic tissue damage called ischemia/reperfusion (IR) injury occurs during the period of reperfusion. Free oxygen radicals and proinflammatory cytokines are responsible for reperfusion injury. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting. The present study aimed to investigate whether IL-18BP had a protective role in remote organ hepatic IR injury.MethodsWistar-Albino rats were divided into three groups that contained seven rats. Group I (sham): Laparotomy and infrarenal abdominal aorta (AA) dissection were done but no clamping was done. Group II (I/R): The infrarenal AA was clamped by atraumatic microvascular clamp for 30 minutes and then was exposed to 90 minutes of reperfusion. Group III (IR + IL-18BP): 75 µg/kg of IL-18BP in 0.9% saline (1 mL) was administered 30 minutes before infrarenal AA dissection and clamping; 30 minutes of ischemia was applied and then was exposed to 90 minutes of reperfusion.ResultsSerum AST, ALT, and LDH levels were remarkably higher in IR group and returned to normal levels in treatment group. The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group. Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP.ConclusionThis study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

Effects of Perilla frutescens on modulations of CYP1A1/2, HO‐1 and activation of Nrf2 in oxidative stress‐induced hepatotoxicity (647.19)

We have previously reported protective effect of Perilla leaves extract (PLE) against tert‐butyl hydroperoxide (t‐BHP)‐induced liver oxidative damage in rats. t‐BHP is known that can be metabolized to free radical intermediates by Phase I enzyme, cytochrome P450s (CYPs), and we speculate that oxidative stress was induced by t‐BHP, which seemed to be closely linked with the oxidative metabolism mediated by CYPs. We examined the effect of the PLE about CYPs related to oxidative stress on enzyme assay such as 7‐ethoxyresorufin 0‐deethylase (EROD, CYP1A1), 7‐methoxyresorufin 0‐demethylase (MROD, CYP1A2), erythromycin N‐demethylase (ERDM, CYP3A), and p‐nitrophenol hydroxylase (PNPH, CYP2E1) in rat liver. The pretreatment of rats with PLE (250, 500 and 1000 mg/kg b.w.) for 5 days before a single dose of t‐BHP (i.p.; 0.5 mmol/kg). PLE was found to be a potent inhibitory effect CYP1A1/2 of oxidative stress‐induced liver. Kinetic analysis of CYP1A1/2 activities demonstrated that PLE inhibited enzyme activities by competitive or noncompetitive mechanism, respectively. Therefore, selective control of CYPs by PLE might contribute to protective effect through inhibitory CYPs activity against oxidative stress in liver. Heme oxygenase‐1 (HO‐1) is an important antioxidant phase II enzyme that plays a critical role in protection against oxidative stress. We confirmed that PLE increased induction of HO‐1 expression as well as activity in t‐BHP‐induced liver. Also, PLE resulted in enhanced nuclear translocation and antioxidant response element (ARE)‐binding of NF‐E2‐related factor 2 (Nrf2) that induce HO‐1.

Effects of Perilla frutescens Extract on Cytochrome P450 Expression in Oxidative Stress‐induced Liver

We have previously reported protective effect of Perilla frutescens extract (PLE) against tert‐butyl hydroperoxide (t‐BHP)‐induced liver oxidative damage in rats. t‐BHP induces lipid peroxidation in rat liver microsomes and it is reported that t‐BHP can be metabolized to free radical intermediates by cytochrome P450 (CYP), which can subsequently initiate lipid peroxidation. We speculate that lipid peroxidation in rat liver microsomes was induced by t‐BHP is closely linked with the oxidative metabolism mediated by CYP1A1/2 and CYP 3A/2E1. We examined the effect of the PLE on CYP activities including Ethoxyresorufin‐O‐deethylase (EROD, CYP1A1), Methoxyresorufin‐O‐deethylase (MROD, CYP1A2), Erythromycin‐N‐demethylase (ERDM, CYP3A) and p‐nitrophenol hydroxylase (PNPH, CYP2E1) under oxidative stress in rat liver. The pretreatment of rats with PLE (250, 500 and 1000 mg/kg b.w.) for 5 days before a single dose of t‐BHP (i.p.; 0.5 mmol/kg), PLE was found to be a potent inhibitory effect CYP 1A1/2 of oxidative stress‐induced liver microsomes. Kinetic analysis of CYP 1A1/2 activity of t‐BHP‐induced microsomes demonstrated that PLE inhibited enzyme activities by competitive or noncompetitive mechanism. These data suggest that selective control of CYP by PLE might contribute to protective effect of liver through inhibitory CYP activities against oxidative stress in rat liver.

Tri-iodothyronine treatment differently affects liver metabolic response and oxidative stress in sedentary and trained rats

We investigated whether swim training modifies the effects of tri-iodothyronine (T3) treatment on the metabolic response and oxidative damage of rat liver. Respiratory capacities, oxidative damage, levels of antioxidants, and susceptibility to oxidative challenge of liver homogenates were determined. Mitochondrial respiratory capacities, rates of H2O2 release, and oxidative damage were also evaluated. Training modified most of the measured parameters in both thyroid states, although the extent of changes was higher in hyperthyroid preparations. T3 treatment enhanced homogenate respiratory capacity, which was further enhanced by training despite the decrease in mitochondrial respiratory capacity. Hormonal treatment also induced liver oxidative damage and glutathione depletion, and increased tissue susceptibility to oxidative challenge. These effects were lower in trained animals. The extensive oxidative damage found in liver homogenates from hyperthyroid sedentary rats was due to low tissue antioxidant protection and high mitochondrial H2O2 production rate, which were increased and decreased respectively by animal training. The training effect on H2O2 production was associated with lower oxidative damage and susceptibility to Ca2+-induced swelling of mitochondria. Measurements with respiratory inhibitors indicated that the differences in H2O2 release in hyperthyroid groups were due to differences in mitochondrial content of autoxidizable electron carrier located at Complex III. We conclude that moderate training is able to reduce hyperthyroid state-linked cellular and subcellular oxidative damage in liver increasing its antioxidant defenses and decreasing the mitochondrial generation of reactive oxygen species.

Targeting of Liposomal Flavonoid to Liver in Combating Hepatocellular Oxidative Damage

The efficacy of mannosylated liposome formulations with Quercetin (QC, a flavonoid antioxidant isolated from indigenous origin) has been tested in vivo against carbon tetrachloride(CCl 4) -induced liver oxidative damage in rats. Single subcutaneous injection of CCl 4 (40% v/v in olive oil; 1 ml/kg) induces the generation of toxic oxygen radicals and results in hepatocellular damage. The increased serum enzyme levels (glutamate pyruvate transaminase, alkaline phosphatase) and hepatocellular conjugated diene levels by CCl 4 induction were significantly lowered due to pretreatment with mannosylated liposomal QC (MLQ) (0.5 ml liposomal suspension containing 0.27 mg QC), whereas the same amount of free QC was found to be ineffective. In addition, the effectiveness of MLQ on CCl 4 -induced acute liver damage also was evaluated by tissue histopathological examination. Damage produced by CCl 4 in liver reverted to normal with pretreatment of MLQ.