Oxidative Stress In Hepatic Tissues Research Articles

Time-dependent changes in oxidative stress biomarkers and activities of lysosomal and antioxidant enzymes in hepatic tissue of rainbow trout (Oncorhynchus mykiss Walbaum) following vaccination against Yersinia ruckeri

Abstract This study analyzed time-dependent effects of vaccination against Y. ruckeri on the oxidative mechanism underlying those effects by detecting relevant lipid peroxidation (2-thiobarbituric acid reactive substances, TBARS) and protein oxidation biomarkers [aldehydic and ketonic derivatives of oxidatively modified proteins (OMP)], antioxidant defenses [activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), total antioxidant capacity (TAC)], as well as activities of lysosomal functioning [alanyl aminopeptidase (AAP), leucyl aminopeptidase (LAP), acid phosphatase (AcP), and β-N-acetylglucosaminidase (NAG)] in hepatic tissue of rainbow trout, Oncorhynchus mykiss (Walbaum) following anti-Y. ruckeri vaccination in the first, second, and sixth months. A concentrated vaccine with Y. ruckeri strains was enclosed in fish feed and was administered three times every other day. Rainbow trout from each group were euthanized 31, 61, and 181 days following vaccination, and hepatic tissue was sampled for analysis. In the current study, vaccination against Y. ruckeri resulted in a no statistically significant change in TBARS levels, while aldehydic and ketonic derivatives of OMP in hepatic tissue decreased, especially after the first and second months following immunization. Moreover, the activities of glutathione-dependent enzymes increased, especially after the first and sixth months. The highest TAC levels were observed two and six months after vaccination. It has been shown that vaccination-related oxidative stress in hepatic tissue is involved in adaptive responses through the temporary mobilization of antioxidant and lysosomal enzymes in rainbow trout. The present study showed the effect of vaccination on lysosome membrane permeability for carbohydrate cleavage after the development of immunity against Yersinia, whereas antioxidant defence was reduced. Our results confirmed that the concept of preserving antioxidant enzyme function after vaccination was also evident when CAT, GR, and GPx activities either increased or were unchanged following vaccination.

The Ameliorative Role of Eugenol against Silver Nanoparticles-Induced Hepatotoxicity in Male Wistar Rats.

Background Silver nanoparticles (AgNPs) utilization is becoming increasingly popular. The existing investigation evaluates the ameliorative impact of eugenol (Eug) against the toxic influences of AgNPs on rats' liver. Methods Sixty adult male rats were enrolled equally into control, Eug (100 mg kg−1 orally), AgNPs-low dose (1 mg kg−1 i.p), AgNPs-high dose (2 mg kg−1 i.p), Eug + AgNPs-low dose (100 mg kg−1 orally + 1 mg kg−1 i.p), and Eug + AgNPs high dose (100 mg kg−1 orally + 2 mg kg−1 i.p). All the groups were treated daily for 30 days, subsequently serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total protein, total albumin, lactate dehydrogenase (LDH), total oxidative capacity (TOC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAC), and interleukin 6 (IL-6) levels were measured; hepatic tissues superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione peroxidase (GPx) levels were evaluated; histopathology and histomorphometry were documented in the liver of all groups; and Bcl-2, P53, Caspase-3, and TNF-α reactive proteins were also immunohistochemically detected. Results AgNPs significantly triggered oxidative stress in hepatic tissues, characterized by elevated levels of AST, ALT, ALP, LDH, TOC, MDA, TNF-α, and IL-6 correlating with considerable decline in total protein, total albumin, TAC, SOD, CAT, GSH, and GPx. These changes were paralleled with histopathological alterations remarkable by devastation of the ordinary hepatic structure, with decrease in the numbers of normal hepatocytes, elevation in the numbers of necrotic hepatocytes, periportal and centrilobular inflammatory cells, deteriorated Kupffer cells, and dilated/congested central and portal veins. Alongside, a marked diminution in Bcl-2 immunoreactivity and a significant elevation in P53, Caspase-3, and TNF-α immunoreactivities were recorded. Supplementation of AgNPs-treated animals with Eug reversed most of the biochemical, histopathological, and immunohistochemical changes. Conclusion This study proposed that Eug has an ameliorative effect against AgNPs-induced hepatotoxicity.

Paeonol Attenuates Hepatic Ischemia/Reperfusion Injury by Modulating the Nrf2/HO-1 and TLR4/MYD88/NF-κB Signaling Pathways.

Hepatic ischemia/reperfusion (HIR) is the most common type of liver injury following several clinical situations. Modulating oxidative stress and inflammation by Nrf2/HO-1 and TLR4/MYD88/NF-κB pathways, respectively, is involved in alleviating HIR injury. Paeonol is a natural phenolic compound that demonstrates significant antioxidant and anti-inflammatory effects. The present study explored the possible protective effect of paeonol against HIR injury and investigated its possible molecular mechanisms in rats. Rats were randomly divided into four groups: sham-operated control, paeonol-treated sham-operated control, HIR untreated, and HIR paeonol-treated groups. The results confirmed that hepatic injury was significantly aggravated biochemically by elevated serum levels of alanine transaminase and aspartate transaminase, as well as by histopathological alterations, while paeonol reduced the increase in transaminases and alleviated pathological changes induced by HIR. Additionally, paeonol inhibited the HIR-induced oxidative stress in hepatic tissues by decreasing the upraised levels of malondialdehyde and nitric oxide and enhancing the suppressed levels of reduced glutathione and superoxide dismutase activity. Furthermore, paeonol activated the protective antioxidative Nrf2/HO-1 pathway. The protective effect of paeonol was associated with inhibiting the expression of the inflammatory key mediators TLR4, MYD88, NF-κB, and TNF-α. Finally, paeonol inhibited the increased mRNA levels of the pro-apoptotic marker Bax and enhanced the reduced mRNA levels of the anti-apoptotic marker Bcl-2. Taken together, our results proved for the first time that paeonol could protect against HIR injury by inhibiting oxidative stress, inflammation, and apoptosis.

Ameliorating effect of Ghrelin on nicotine induced oxidative stress in liver tissue morphology in BALB/c mice.

Background: Nicotine, a naturally occurring alkaloid is the predominant chemical among the constituents in cigarette smoke. Consumption forms include smoke (cigarettes, pipes and cigars) and smokeless tobacco (chewable tobacco). Aim: To determine the effect of ghrelin in nicotine induced liver toxicity in BALB/c mice. Study Design: Randomized Control Trial. Methodology: Present study enrolled 90 male BALB/c mice Group I (control group) was given standardized laboratory diet and intraperitoneal injection (i.p) of normal saline. Group II was given standardized laboratory diet and nicotine at a dose of 2.5mg/ kg body weight (i.p), while Group III was given standardized laboratory diet plus nicotine a dose of 2.5mg/ kg body weight (i.p) along with ghrelin at a dose of 10µg/kg on alternate days for 4 weeks. On 30th day sampling was done for hepatic tissue oxidative stress enzymes (superoxide dismutase, glutathione reductase and catalase levels), and histology of liver tissue for assessment of hepatic tissue damage and recovery. Results: Nicotine group showed evident hepatic damage with significant increase in liver oxidative stress markers. On histological examination, liver showed mild to moderate grade necro-inflammation. Administration of ghrelin partially restored the oxidative stress markers and inflammatory histological changes due to nicotine induced toxicity. Conclusion: We concluded that Ghrelin appears to be hepatoprotective due to its antioxidant and anti-inflammatory properties. Keywords: Nicotine, Ghrelin, Oxidative Stress, Antioxidant Enzymes and Necro-Inflammation

Hepatoprotective and therapeutic effects of resveratrol: A focus on anti-inflammatory and antioxidative activities.

Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti-inflammatory, anti-apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro-inflammatory cytokines like TNF-α, IL-1α, IL-1β, and IL-6. It also inhibits the transcription factor nuclear NF-κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti-inflammatory, and anti-fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.

Quercetin ameliorates acetamiprid-inducedhepatotoxicity and oxidative stress

Introduction: Neonicotinoids are a new type of insecticides that have been introduced to the poison market during the last three decades. Acetamiprid (ACT) is a neonicotinoid and widely used for controlling pests. It targets the liver as a toxic agent and damages hepatic tissues through oxidative stress mechanisms. Quercetin is a flavonoid with potent antioxidant and hepatoprotective activity and protects tissues from oxidative damages. Thus, this study is aimed to assess the protective effect of quercetin on acetamiprid-induced hepatotoxicity. Methods: Thirty-six Wistar rats were classified into six groups including control, DMSO, ACT 20, ACT 40, quercetin, and ACT40+quercetin. All treatments were administered orally with gavage for 28 days. Alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) enzyme activity was measured in serum as biomarkers of hepatotoxicity. Lipid peroxidation, superoxide dismutase (SOD) enzyme activity and total thiol content were measured in hepatic tissues. Also, hepatic tissue sections were prepared and stained with hematoxylin and eosin and evaluated under optic microscope for any tissue injuries. Results: Findings showed that ACT, especially in high dose (40mg/kg), induced hepatic tissue destruction associated with increased hepatic enzyme activity, except ALP activity, in the serum. Besides, ACT increased the lipid peroxidation and decreased total thiol content and SOD activity, which indicates ACT-induced oxidative stress in hepatic tissues. Also, hepatic tissue injuries were observed in ACT-treated group. All these changes in liver were prevented by quercetin. Conclusion: Because of strong antioxidant properties, quercetin can cope effectively with ACT-induced hepatotoxicity.

Hepatoprotective effect of arjunolic acid against cisplatin-induced hepatotoxicity: Targeting oxidative stress, inflammation, and apoptosis.

Minimizing the adverse effects of chemotherapeutic agents remains a therapeutic challenge. Cisplatin (CP) induces hepatotoxicity through activation of oxidative stress, inflammation, and apoptosis cascades which is considered a significant drawback. Thus, this study aimed to highlight the possible hepatoprotective role of arjunolic acid (Arj) in a rat model of CP-induced hepatotoxicity. Four groups of rats were included; the normal control group, Arj control group, CP group which was injected with 7.5 mg/kg CP intraperitoneally to induce hepatotoxicity, and the treated group (Arj + CP), which was orally administered 20 mg/kg Arj for 10 days with a CP hepatotoxic dose on day 5. Blood and liver tissues were assembled for analysis at the end of the study. Pretreatment with Arj exhibited a marked improvement in liver function as well as histopathology when compared with the CP group. Moreover, Arj suppressed the oxidative stress in hepatic tissue by significantly decreasing malondialdehyde and nitric oxide contents along with markedly elevating the levels of superoxide dismutase, catalase, and reduced glutathione when compared with CPinjected rats. Attenuation of hepatic inflammation and apoptosis was also reported with Arj treatment through the marked reduction in the proinflammatory cytokine tumor necrosis factor α level as well as the apoptotic marker caspase-3 protein expression in comparison to the CP group. This study explored for the first time the Arj hepatoprotective effect against CP-induced hepatotoxicity through its antioxidant, anti-inflammatory, and antiapoptotic activities.

Diacerein protects rats with liver ischemia/reperfusion damage: Down-regulation of TLR4/ NFκ-B signaling pathway

PurposeLiver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. MethodsAdult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. ResultsDiacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. ConclusionThese results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Antifibrotic effects of bezafibrate and pioglitazone against thioacetamide-induced liver fibrosis in albino rats.

Activation of hepatic stellate cells is a central event in hepatic fibrogenesis that offers multiple potential sites for therapeutic interventions. Peroxisome proliferator-activated receptors are implicated in liver fibrosis. We aimed to evaluate the effect of bezafibrate and pioglitazone on a thioacetamide (TAA) rat model of liver fibrosis and to clarify the possible underlying mechanisms. Rats received intraperitoneal injections of TAA for 6 weeks. Daily oral treatments with bezafibrate or pioglitazone were started with the first day of TAA intoxication. Serum liver function tests, hepatic malondialdehyde (MDA), total nitrite and nitrate (NOx), superoxide dismutase, and hepatic histopathology were assessed to evaluate hepatic damage. Alpha smooth muscle actin (α-SMA) and tissue inhibitor metalloproteinase-1 (TIMP-1) and caspase-3 were also assessed. The TAA group experienced significant deterioration of liver functions, increased oxidative stress, and increased liver tissue NOx. Administration of bezafibrate or pioglitazone resulted in significant improvement of all liver functions and reduced oxidative stress in hepatic tissues. Only administration of bezafibrate significantly reduced NOx levels. Liver tissues from the TAA-treated group showed disrupted normal architecture. Administration of bezafibrate or pioglitazone attenuated this picture. Stronger α-SMA expression was detected in the TAA group. Treatment with bezafibrate or pioglitazone decreased the α-SMA expression.

Isopulegol Mitigates Hyperglycemia Mediated Oxidative and Endoplasmic Reticulum Stress in HFD/STZ Induced Diabetic Rats

Oxidative and endoplasmic reticulum stresses contribute to the pathogenesis of β-cell dysfunction in diabetes mellitus. This study investigates the effect of isopulegol on the above stresses in HFD/STZ induced diabetic rats. Animals in group I and II were placed in normal pellet diet and group II was treated with isopulegol at 200mg/kg b.w. Animals in groups III-V were placed in HFD for 4weeks and made diabetic with single intraperitoneal injection of STZ (35mg/kg b.w) in 0.1M citrate buffer (pH 4.5). Group III served as diabetic control while animals in group IV and V were treated with isopulegol (100mg/kg b.w) and metformin (25mg/kg b.w) respectively for 28d. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione sulphur transferase (GST), glutathione reductase (GR) and the levels of vitamin-E, vitamin-C, reduced glutathione (GSH) were significantly (p <0.05) decreased in plasma and tissues of diabetic rats. Thiobarbituric acid reactive acid substances (TBARS) and lipid hydroperoxides (LHP), indices of lipid peroxidation were also significantly (p <0.05) increased in diabetic rats. In pancreatic tissue ER stress markers PERK, elf2α, ATF4 and in hepatic tissue oxidative stress marker UCP-2 expression was significantly (p <1.0) increased in diabetic rats. Administration of isopulegol significantly improved antioxidant status and decreased oxidative and ER stress markers in diabetic treated rats. Histopathological studies on liver and kidney supported the above findings. The results are comparable with the standard drug metformin. Isopulegol a naturally occurring monoterpene alcohol attenuated oxidative and ER stress in HFD/STZ induced diabetic rats.

The preventive effect of atorvastatin on liver fibrosis in the bile duct ligation rats via antioxidant activity and down-regulation of Rac1 and NOX1.

Objective(s):Atorvastatin is a cholesterol-lowering agent capable of inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. Recent studies have demonstrated new facets of atorvastatin, such as antioxidant and anti-fibrotic properties. We investigated the effect of atorvastatin on hepatic injury via the measurement of the antioxidant capacity and protein expression of NOX1, Rac1-GTP, and Rac1 in a rat biliary duct ligation (BDL) model.Materials and Methods:This study is regarded as experimental interventional research in which a total of 32 adult male Wistar rats (200-250 g) were assigned to 4 groups (eight rats per group) as follows: Control group; Control + At group (15 mg\\kg\\day atorvastatin); BDL group, and BDL+ At group (15 mg\\kg\\day atorvastatin). Expression levels of Rac1, NOX1, and Rac1-GTP were determined by western blot analysis. Besides, specific biomarkers of oxidative stress in hepatic tissues of all animals were also analyzed.Results:Atorvastatin reduced liver injury via a decrease in the expression of NOX1, Rac1-GTP, and Rac1 in the BDL group (P<0.05), while the increased contents of protein thiol groups were observed, and the protein carbonylation was decreased in atorvastatin-treated BDL rats compared to the BDL group (P<0.05). Also, administration of atorvastatin in the BDL group significantly lowered oxidative stress through increasing the activity of catalase and superoxide dismutase in comparison with the BDL group (P<0.05). Conclusion:It seems that atorvastatin has potential advantages in mitigation of liver fibrosis by a decrease in the expression of NOX1, Rac1-GTP, and Rac1, along with, a reduction in oxidative stress of liver tissues in rats induced by BDL.

Cnidoscolus aconitifolius (Mill.) I. M. Johnst leaf extract prevents oxidative hepatic injury and improves muscle glucose uptake ex vivo.

Total phenol, total flavonoid, and ameliorative potentials of aqueous leaf extract of Cnidoscolus aconitifolius in Fe2+ -induced oxidative stress in hepatic tissue and muscle glucose uptake using ex vivo models were assessed. These were carried out using standard procedures. The results revealed that the extract showed the presence of total phenol and total flavonoid, as well as free radicals scavenging abilities in a dose-dependent manner. Also, the aqueous leaf extract of C. aconitifolius enhanced Fe2+ -induced oxidative injury in hepatic tissue by considerably reducing the concentration of lipid peroxidation, with improvement in the activities of catalase and superoxide dismutase in a dose-dependent manner. In addition, the extract enhanced glucose uptake in psoas muscle. It can be deduced from this study that the extract might be beneficial to people with diabetes mellitus. PRACTICAL APPLICATIONS: Aqueous leaf extract of Cnidoscolus aconitifolius displayed the presence of total phenol and total flavonoid, as well as an increase in free radical scavenging activities in a dose-dependent manner. The plant extract also improved Fe2+ -induced oxidative injury in hepatic tissue by decreasing lipid peroxidation concentration, improved the activities of catalase as well as superoxide dismutase, with enhancement in glucose uptake of psoas muscle in a dose-dependent manner.

Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Chloroform extract of Argemone mexicana

Aim: The present study was undertaken to examine the effects of Chloroform extract of Argemone mexicana using the paracetamol-induced liver damage in rats as the animal model.&#x0D; Materials and methods: Chloroform extract of Argemone mexicana (100 and 200 mg/kg body weight) was administered daily in experimental animals. The hepatoprotective efficacy of Chloroform extract of Argemone mexicana (100 and 200 mg/kg) was investigated against paracetamol-induced hepatotoxicity. The levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), serum alkaline phosphatase (ALP), bilirubin and triglycerides were estimated. Moreover, chloroform extract of Argemone mexicana -aided antioxidant defense against hepatotoxic insult of paracetamol was measured by evaluating a number of anti-oxidative biomarkers including reduced malondialdehyde (MDA) in the serum.&#x0D; Results: Oral administration of paracetamol (500 mg/kg b.wt.) resulted in a significant elevation of liver enzymes in serum such as SGOT, SGPT, ALP, bilirubin and triglyceride levels when compared with the results in the control group. As regards oxidative stress biomarkers, there were increased tissue levels of malondialdehyde in the group treated with paracetamol. All of these results were ameliorated by co-administration of chloroform extract of Argemone mexicana.&#x0D; Conclusions: These results suggest that the protective role of Chloroform extract of Argemone mexicana in the prevention of PCM-induced hepatic toxicity in rats was associated with a decrease of oxidative stress in hepatic tissues.&#x0D; Keywords: Antihepatotoxicity; Chloroform extract of Argemone mexicana; Paracetamol

Rooibos tea (&lt;i&gt;Aspalathus linearis&lt;/i&gt;) extract protects against air particulate matter induced hepatic oxidative stress in Nrf2-independent manner

Diesel exhaust particles (DEP) are a typical example of air particulate matter generated into the environment from industrial, residential and vehicular diesel engines. Studies have implicated the induction of oxidative stress in the adverse health effect of DEP. In this study, the effect of aqueous rooibos extract (RE) on DEP-induced hepatic oxidative stress was examined and the role of Nrf2-regulation in this effect was evaluated. Wistar rats were divided into 4 groups of 5 rats/group and were administered 0.7 mg/kg DEP subcutaneously and 50 mg/kg RE orally. Group one was given vehicle (saline and DMSO), group two was administered with RE for 4 weeks, group three was given RE for 2 weeks followed by concomitant administration of RE and DEP for further 2 weeks and group four was given DEP twice a week at the last 2 weeks of treatment. Malondialdehyde (MDA), Conjugated dienes (CDs) and GSH levels were determined in the liver homogenate. AST and ALT activities were assayed in the serum and RT-qPCR was used to quantify the gene expression of Nrf2 and HO-1 in the liver. Results showed that RE pre-treatment significantly (p<0.001) decreased DEP-induced elevated serum AST and ALT levels, decreased DEP-induced MDA (p<0.001) and CDs (p<0.05) levels.DEP caused significant (p<0.05) decrease in GSH levels, which was reversed by rooibos extract pre-treatment. DEP also caused significant induction in Nrf2 and HO-1 mRNA levels. However, these inductions were significantly attenuated by RE. In summary, rooibos extract has the potential to protect against DEP-induced oxidative stress in hepatic tissues probably by a mechanism which may not involve activation of the Nrf2-dependent response. Keywords : Oxidative stress; diesel exhaust particles; rooibos tea; hepatic tissue

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response

Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on immunoregulation, tissue repair, and regeneration from the bench to the bedside. Increasing evidence demonstrates that extracellular vesicles (EVs) derived from MSCs could contribute to these effects and are considered as a potential replacement for stem cell-based therapies. However, the efficacy and underlying mechanisms of EV-based treatment in hepatic ischemia-reperfusion injury (IRI) remain unclear. Here, we demonstrated that human umbilical cord MSC-EVs (huc-MSC-EVs) could protect against IRI-induced hepatic apoptosis by reducing the infiltration of neutrophils and alleviating oxidative stress in hepatic tissue in vivo. Meanwhile, huc-MSC-EVs reduced the respiratory burst of neutrophils and prevented hepatocytes from oxidative stress-induced cell death in vitro. Interestingly, we found that the mitochondria-located antioxidant enzyme, manganese superoxide dismutase (MnSOD), was encapsulated in huc-MSC-EVs and reduced oxidative stress in the hepatic IRI model. Knockdown of MnSOD in huc-MSCs decreased the level of MnSOD in huc-MSC-EVs and attenuated the antiapoptotic and antioxidant capacities of huc-MSC-EVs, which could be partially rescued by MnSOD mimetic manganese (III) 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP). In summary, these findings provide new clues to reveal the therapeutic effects of huc-MSC-EVs on hepatic IRI and evaluate their preclinical application.-Yao, J., Zheng, J., Cai, J., Zeng, K., Zhou, C., Zhang, J., Li, S., Li, H., Chen, L., He, L., Chen, H., Fu, H., Zhang, Q., Chen, G., Yang, Y., Zhang, Y. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response.

Concentrated hot water-infusion of phragmanthera incana improves muscle glucose uptake, inhibits carbohydrate digesting enzymes and abates Fe2+-induced oxidative stress in hepatic tissues.

Chronic hyperglycemia has been implicated in the development of oxidative stress and as a major factor in etiology of secondary complication in diabetes. In the present study, the antidiabetic potential of Phragamenthra incana (P. incana) hot infusion and its possible inhibitory effects on carbohydrate digesting enzymes, promotion of muscle glucose uptake, and the antioxidative potentials in Fe2+-induced oxidative stress in hepatic tissue were investigated. The infusion significantly (p < 0.05) scavenged free radicals (DPPH) and displayed favourable ferric reducing antioxidant power (FRAP) with increasing concentrations. It also significantly ameliorated Fe2+-induced oxidative stress in hepatic tissues by increasing superoxide dismutase (SOD) and catalase activities and depleting malondialdehyde (MDA) level. The results further showed that the infusion significantly (p < 0.05) inhibited α-amylase and α-glucosidase activity, and enhanced muscle glucose uptake, with and without insulin. Liquid Chromatography-Mass Spectroscopy (LCMS) analysis of the infusion revealed the presence of 2-methoxythiazole; l-cysteine; nicotinic acid; S-methyl-l-cysteine; isoquinoline, 1-methyl-; and 1H-indole-2,3-dione,5-methyl. The results of this study suggest that the observed antidiabetic and antioxidative potentials of P. incana could be attributed to its identified phytochemical constituents, however, this supports folkloric medicinal use of this plant.

Histopathological changes and oxidative damage in hepatic tissue of rats experimentally infected with Babesia bigemina.

The present study was aimed to investigate oxidative stress, DNA damage, and histopatholog- ical alterations in hepatic tissues of splenectomized Wistar rats experimentally infected with Ba- besia bigemina. Rats were challenged with 5x106 infected erythrocytes. Babesia infection was con- firmed both with Giemsa's staining blood smears and nested-PCR amplified region of apical membrane antigen-1 (AMA-1) gene. Parasitemia reached approximately 10 % at day 5 post-in- fection. Livers of infected rats were enlarged and darker in color, became extremely brittle with marked congestion. Microscopic evaluation showed cytoplasmic clearing of hepatocytes and se- vere hydropic changes with significantly dilated sinusoids containing macrophages and also intra- sinosoidal parasitized erythrocytes. Severe infiltration of lymphoplasma cells was also present throughout the liver parenchyma. Furthermore, Kupffer cells were enlarged and, occasionally, containing Babesia-parasitized erythrocytes. The activity of Glutathione (GSH) and catalase (CAT), and total antioxidant capacity (TAC) were also significantly decreased (p ⟨ 0.05) after infection of rats with B. bigemina. B. bigemina infection also induced a significant increase (p ⟨ 0.05) in hepatic malondialdehyde (MDA) and nitric oxide-derived products (NOx) concentra- tions as well as amount of endogenous hepatocytes DNA damage. Hepatic damage was also re- flected through the measurement of lactic acid dehydrogenase (LDH) and protein carbonyl con- tent (PCO) in liver cells. These two indices of liver injury were also significantly elevated (p ⟨ 0.5) during B. bigemina infection. Evaluation of correlation between assayed variables in infected rats revealed that MDA levels were positively correlated with PCO, NOx, LDH and DNA damage in the infected group and negatively correlated with GSH, CAT and TAC. There was also an inverse relationship between the antioxidant enzymes activities of GSH, CAT and TAC with PCO, NOx and DNA damage in infected rats. However, NOx showed positive correlation with PCO and DNA damage in infected rats. On the basis of the above results it can be concluded that the Ba- besia infection increases oxidative stress markers, protein carbonyl content and DNA damage and decreases antioxidant enzymes activities in the liver. These results suggest that B. bigemina infec- tion could alter the liver histopathology and causes DNA damage following oxidative stress in hepatic tissue. Further studies are needed to precisely define how hepatic tissue damage takes place in B. bigemina infection.

Protective Effect of Long Term Administration of Gum Arabic on Oxidative Stress in Hepatic Tissue of Diabetic Rats

Protective Effect of Long Term Administration of Gum Arabic on Oxidative Stress in Hepatic Tissue of Diabetic Rats

Innovative perception on using Tiron to modulate the hepatotoxicity induced by titanium dioxide nanoparticles in male rats

The extensive application of titanium dioxide nanoparticles (TiO2 NPs) in the food industry arouses a debate regarding the probable risk associated with their use. Several recent studies reported that most nanoparticles (NPs) have adverse actions on the liver. The objective of this study is to examine whether Tiron plays a modulatory role against apoptotic damage induced by TiO2 NPs in rat livers. Forty rats were randomly divided into 4 groups; a control group received phosphate-buffered saline, an intoxicated group received 100 mg/kg/day of TiO2 NPs for 60 days, a treated group received 470 mg/kg/day of Tiron for the last 14 days after TiO2 NPs administration, and a Tiron group received Tiron only as previously mentioned. Oral administration of TiO2 NPs significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). In the liver, TiO2 NPs increased oxidative stress through increasing lipid peroxidation and decreasing GSH concentration and the levels of the SOD and GPx enzymes. TiO2 NPs significantly upregulated the proapoptotic Bax gene and downregulated the antiapoptotic Bcl-2 gene. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Apoptotic lesions were also obvious in this group. Treatment with Tiron as an antioxidant significantly decreased serum biochemistry, ameliorated oxidative stress in hepatic tissue, upregulated Bcl-2, decreased Bax expression and attenuated the histopathology of hepatic injury. These findings indicate that Tiron effectively diminishes the hazardous effects of TiO2 NPs on rat liver.

Hepatoprotective Effects of Aqueous Extract of Watermelon (Citrullus lanatus) Seeds on Ethanol-Induced Oxidative Damage in Wister Rats

Background: Watermelon (Citrullus lanatus) is a roundish or ovoid fruit rich in antioxidant supplements that prevent oxidative stress in hepatic tissues due to generation of reactive oxygen species following exposure to alcohol. The present study aimed to investigate the protective effects of watermelon seed on ethanol-induced oxidative damage in liver of Wister rats. Methods: Twenty-five adult Wister rats of both sexes were randomly divided into five groups of five rats each. Rats in group I were administered distilled water for 8 days. Group II were administered distilled water for 7 days followed by 20 mL/kg body weight of 40% ethanol per body weight on day 8. Groups III and IV were administered 200 and 400 mg/kg, respectively, of the extract for 7 days followed by 20 mL/kg of 40% ethanol on day 8. Group V received 100 mg/kg body weight of silymarin for 7 days followed by 20 mg/kg of 40% ethanol on day 8. Animals were sacrificed on day 8. Liver was excised and then processed for histopathological examination. Biochemical assay for the following hepatic marker enzymes was carried out: alanine amino-transferase (ALT), aspartate amino-transferase (AST), alkaline phosphates (ALP), and protein concentration. Results: The results showed that watermelon treatment leads to increase in body weight. Furthermore, pretreatment with watermelon seed extract lead to significant decrease (P < 0.05) in plasma AST, ALT, ALP, and protein concentration, compared to ethanol treatment group. Conclusion: Watermelon seed extract demonstrates hepatoprotective effect in ethanol-induced oxidation in the liver of Wister rats, which might be linked to various antioxidant phytochemical content present in the extract.