Oxidative Stress In Liver Tissue Research Articles

Silibinin's Effects against Methotrexate-Induced Hepatotoxicity in Adjuvant-Induced Arthritis Rat Model.

Methotrexate (MTX) is the first drug of choice to treat several diseases, including rheumatoid arthritis. However, its administration is accompanied by severe side effects, most commonly hepatotoxicity. Hence, alternative therapies with a lower toxicity and fewer side effects are needed. This study aimed to investigate the antioxidant and hepatoprotective effects of silibinin (SIL, natural agent) against MTX-induced hepatotoxicity in an adjuvant-induced arthritis (AIA) rat model. Arthritic rats were treated with SIL (100 mg/kg) and/or methotrexate (2 mg/kg). Non-arthritic rats, arthritic untreated rats, and arthritic rats who received the vehicle were followed in parallel. SIL alleviated the systemic consequences of arthritis by restoring lost weight, decreasing the erythrocyte sedimentation rate, and ameliorating joint damage, which was evident both micro- and macroscopically. Additionally, SIL prevented the histopathological alterations in the liver and significantly reduced the liver damage caused by MTX and AIA, as shown by a decrease in the markers of liver damage (ALT and AST). Furthermore, SIL relieved the oxidative stress induced by AIA and MTX in liver tissue by decreasing the lipid peroxidation (MDA) levels and enhancing the antioxidant defense system (GSH levels; catalase and superoxide dismutase (SOD) activities). In conclusion, our results suggest that SIL is a potent antioxidant and hepatoprotective agent in arthritic rats. It markedly attenuated the progression and severity of the arthritic disease and eased the oxidative stress in liver tissue by improving the pro-oxidant/antioxidant balance.

Acetaminophen overdose causes a breach of the blood-bile barrier in mice but not in rats.

Acetaminophen (APAP) is known to cause a breach of the blood-bile barrier in mice that, via a mechanism called futile bile acid (BA) cycling, increases BA concentrations in hepatocytes above cytotoxic thresholds. Here, we compared this mechanism in mice and rats, because both species differ massively in their susceptibility to APAP and compared the results to available human data. Dose and time-dependent APAP experiments were performed in male C57BL6/N mice and Wistar rats. The time course of BA concentrations in liver tissue and in blood was analyzed by MALDI-MSI and LC-MS/MS. APAP and its derivatives were measured in the blood by LC-MS. APAP-induced liver damage was analyzed by histopathology, immunohistochemistry, and by clinical chemistry. In mice, a transient increase of BA in blood and in peri-central hepatocytes preceded hepatocyte death. The BA increase coincided with oxidative stress in liver tissue and a compromised morphology of bile canaliculi and immunohistochemically visualized tight junction proteins. Rats showed a reduced metabolic activation of APAP compared to mice. However, even at very high doses that caused cell death of hepatocytes, no increase of BA concentrations was observed neither in liver tissue nor in the blood. Correspondingly, no oxidative stress was detectable, and the morphology of bile canaliculi and tight junction proteins remained unaltered. In conclusion, different mechanisms cause cell death in rats and mice, whereby oxidative stress and a breach of the blood-bile barrier are seen only in mice. Since transient cholestasis also occurs in human patients with APAP overdose, mice are a clinically relevant species to study APAP hepatotoxicity but not rats.

Ozone Exposure Controls Oxidative Stress and the Inflammatory Process of Hepatocytes in Murine Models.

(1) Background: Ozone exposure is a promising tool for treating liver damage since it is known to control the release of free radicals and increase the expression of antioxidant enzymes. The objective is to investigate the main intracellular pathways activated after exposure to ozone, considering the dosage of antioxidant enzymes and markers of oxidative stress. (2) Methods: This systematic review was performed based on the PRISMA guidelines and using a structured search in MEDLINE (PubMed), Scopus, and Web of Science. Bias analysis and methodological quality assessments were examined using the SYRCLE Risk of Bias tool. (3) Results: Nineteen studies were selected. The results showed that the exposure to ozone has a protective effect on liver tissue, promoting a decrease in inflammatory markers and a reduction in oxidative stress in liver tissue. In addition, ozone exposure also promoted an increase in antioxidant enzymes. The morphological consequences of controlling these intracellular pathways were reducing the tissue inflammatory process and reducing areas of degeneration and necrosis. (4) Conclusions: Ozone exposure has a beneficial effect on models of liver injury through the decrease in oxidative stress in tissue and inflammatory markers. In addition, it regulates the Nrf2/ARE antioxidant pathway and blocks the NF-κB inflammatory pathway.

Stress-Related Gene Expression in Liver Tissues from Laying Hens Housed in Conventional Cage and Cage-Free Systems in the Tropics.

Global egg production is mainly based on cage systems, which have been associated with negative effects on the welfare of birds. Stress factors in restrictive production systems can lead to changes in gene transcription and protein synthesis, ultimately impacting the quality of poultry products. The liver serves various metabolic functions, such as glycogen storage, and plays a crucial role in animals' adaptation to environmental changes. Consequently, both internal and external conditions can influence liver functions. The aim of this study was to evaluate the gene expression of AGP, CRP, NOX4, SOD1, CAT, GPX1, SREBF1, and FXR in the liver of laying hens under two different production systems. Liver tissues from Hy-Line Brown hens housed in conventional cage and cage-free egg production systems at 60 and 80 weeks of production were used. mRNA transcript levels were determined by qPCR using the relative quantification method and ACTB as the reference gene. AGP, SOD1, and SREBF1 gene expressions were significantly higher in the conventional cage group at the 60 weeks of production. Furthermore, the mRNA levels of transcripts related to oxidative stress and lipid metabolism were higher in the group of laying hens housed in conventional cages compared to those in cage-free systems. These results suggest differential gene expression of genes related to oxidative stress in liver tissues from hens housed in conventional cages compared to cage-free systems. The conditions of the egg production system can impact the gene expression of oxidative stress and lipid synthesis genes, potentially leading to changes in the metabolism and performance of hens, including egg quality.

Potential effect dietary supplementation of calcium tetraborate in quails exposed to cadmium: Its impact on productive performance, oxidative stress, cecal microflora, and histopathological changes

Cadmium (Cd) is a ubiquitous environmental pollutant, and Cd exposure harms human health, agriculture, and animal husbandry. The present study aimed to investigate the potential protective effect of dietary supplementation of calcium tetraborate (CTB) on productive performance, oxidative stress, cecal microflora, and histopathological changes in quail exposed to Cd. A total of one hundred twenty, 6-week-old Japanese quail (four females and two males/replicate) were divided into four groups (30 quails/group): the control group (feeding basic diet), CTB group (basic diet containing 300 mg/kg CaB4O7, 22.14% elemental B/kg diet), the Cd group (basic diet containing 100 mg/kg cadmium chloride (CdCl2) (total Cd content of 92.1 mg/kg)) and the CTB + Cd group (basic diet containing 300 mg/kg CTB and 100 mg/kg CdCl2). The results showed that Cd exposure caused decreased performance, increased the proportion of broken and soft-shelled eggs, induced oxidative stress, affected cecal microflora, epicardial hemorrhages in the heart, focal necrosis in the liver, degeneration in the kidneys, and degenerated and necrotic seminiferous tubules in the testicles. CTB prevented Cd-induced oxidative stress in liver tissue by increasing total antioxidant status and reducing total oxidant status. In addition, CTB improved egg production and feed conversion ratio (FCR). CTB protected the cecal microflora by inhibiting Enterobacteriaceae and promoting Lactobacillus. CTB also reduced Cd-induced histopathological damage in the heart, liver, kidneys, and testicles. In conclusion, these findings suggest that CTB could be used in Cd-challenged quail, and this compound provides new insights into the toxicity of environmental Cd.

Protective Effect of Pomegranate Juice on Lead Acetate-Induced Liver Toxicity in Male Rats

Objective: Lead has been reported to cause oxidative stress in liver tissues and cause histopathological changes. Studies have shown that pomegranate juice has antioxidant properties that prevent oxidative stress. In this study, the harmful effects of lead acetate on rat liver tissue and the efficacy of pomegranate juice against these effects were investigated. Methods: 28 male Wistar albino rats were divided into four groups: control, lead acetate (50 mL/kg), pomegranate juice (1 mL/kg), and lead acetate + pomegranate juice (50 mL/kg+1 mL/kg). Lead acetate and pomegranate juice were administered orally. Results: When compared with the control group, it was seen that the lead acetate had an increase in the malondialdehyde level and a decrease in reduced Glutathione, Glutathione S-transferase, and Carboxylesterases. Group lead acetate + pomegranate juice had a reduction in malondialdehyde level and an increase in Glutathione, Glutathione S-transferase, and Carboxylesterases compared with the group lead acetate. The lead level of group lead acetate + pomegranate juice decreased compared to the group lead acetate. Cellular degeneration and irregular hepatic cords were observed in group lead acetate's liver tissue, and the negative changes were lost in group lead acetate + pomegranate juice. Conclusion: It was observed that pomegranate juice had a protective effect against liver toxicity caused by lead acetate.

Protective effects of empagliflozin on methotrexate induced hepatotoxicity in rats

Methotrexate (MTX), a folic acid antagonist, is commonly prescribed as a cytotoxic drug to treat several conditions such as leukemia and inflammation-related diseases, including rheumatoid arthritis and psoriasis. However, its use in clinical practice has been limited due to its fatal side effects, especially hepatotoxicity. Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has recently been reported to exhibit anti-inflammatory and anti-oxidative properties. This study was aimed to evaluate the effect of Empagliflozin on liver injury induced by MTX in rats. The rats were divided into five groups as control, MTX (20 mg/kg; i.p.), Empagliflozin (30 mg/kg/day; i.p.), MTX and Empagliflozin (10 and 30 mg/kg/day; i.p.). Histopathologic alterations were examined for assessment of the liver injury. Furthermore, the levels of tissue malondialdehyde (MDA) and activity of anti-oxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated. Our results revealed that treatment with Empagliflozin significantly improved histopathologic alterations, and elevated levels of AST and ALT induced by MTX administration. Additionally, altered activities of SOD, GPx, and catalase were significantly improved followed by Empagliflozin treatment. However, the higher dose of Empagliflozin was observed to have several benefits compared to the lower dose. Our data suggest that Empagliflozin might possess a protective role against MTX-induced hepatotoxicity by inhibiting oxidative stress in liver tissue.

Hepatoprotective effect of ethanolic extract of Syzygium polyanthum in rats induced by rifampicin and isoniazid

Introduction: Syzygium polyanthum (Bay leaf) is one of the species of the family Myrtaceae used as a seasoning and medicine, especially in Southeast Asia such as Malaysia and Indonesia. This leaf is known to have medicinal properties to prevent cholesterol, diabetes mellitus, hypertension, gastritis, diarrhea, and gout. This study evaluates the hepatoprotective properties of the ethanolic extract of Syzygium polyanthum in rats induced by rifampicin and isoniazid. Methods: These hepatoprotective properties were evaluated by the assay of liver function parameters, such as total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), the histopathological study of the liver and malondialdehyde (MDA) as a marker of stress oxidative. Results: Administration of ethanolic extract of Syzygium polyanthum has no significant effect (P>0,05) on total bilirubin, SGOT, and SGPT, but can reduce MDA descriptively. Ethanolic extract of Syzygium polyanthum could not cure the liver tissue of rats in histopathology examination. It means that ethanolic extract of Syzygium polyanthum can help to reduce oxidative stress in liver tissue. Conclusion: In further research, it is recommended to develop other bioactivity tests from bay leaf isolates and conduct more specific studies to explain the mechanism of action of the extract at the cellular and organismal levels that are more complex, as well as toxicity tests to determine pharmacological effects.

Combinational Antidiabetic effects of Curcuma longa L. and Trigonella foenum-graecum L. extracts in alloxan induced type-1 diabetic rats

Diabetes mellitus is a metabolic disorder that is one of the leading causes of death globally. The current study aimed to determine the combined protective effect of Curcuma longa (CL) and Trigonella foenum-graecum (TFG) on alloxan-induced oxidative stress in liver tissue of albino Wister rats. Rats were divided into 8 groups with 6 individuals each. Group I served as control, group II, III and IV were treated with CL, TFG and CL+TFG respectively. Group V, VI, VII and VIII were alloxan-induced diabetic rats, whereas group V served as negative control and group VI, VII and VIII were treated with CL, TFG and CL+TFG respectively. Blood glucose, body weight, oxidative enzymes and histopathological changes were evaluated. Group V showed significant increase in blood glucose levels after induction of alloxan, whereas, group VI, VII and VIII showed significantly decreased levels. However, the best hypoglycaemic activity was found in group VIII. The body weights were slightly increased in groups II, III and IV after the treatment of plant extracts, whereas, decreased body weights were noticed in group V. though no significant weight changes were observed in groups VI, VII and VIII. A significant decrease in oxidative enzyme levels as compared to group V were recorded. The histopathological investigation of liver tissue showed morphological alteration in group V and ameliorative effects in group VI, VII and VIII due to administration of CL, TFG and CL+TFG. Therefore, the combined administration of CL+ TFG exhibits the highest hypoglycemic activity by reducing the oxidative enzyme levels and regeneration of liver tissue.

Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-β1/Smad3 pathways

BackgroundSepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1β/Smad3 pathways. MethodsA septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism. ResultsDCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-β1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway. ConclusionsDCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.

Hibiscus-cisplatin combination treatment decreases liver toxicity in rats while increasing toxicity in lung cancer cells via oxidative stress- apoptosis pathway

Cisplatin (CIS) is a broad-spectrum anti-carcinogen that causes cytotoxic effects both in normal and cancer cells. The purpose of this study was to test whether Hibiscus sabdariffa (HS) extract can reduce CIS-induced hepatotoxicity in rodents and to assess its anticancer activity in vitro. Treatment with HS extract at daily doses of 500 mg/kg before and after a single dose of CIS (10 mg/kg) reduced hepatotoxicity in Wistar male albino rats. HS extract reduced activity of hepatic damage marker enzymes ( i.e. alanine and aspartate aminotransferases), necrosis, and apoptosis in liver tissues of CIS-treated rats. This hepatic protection was associated with reduced oxidative stress in liver tissues. The antioxidant effects of HS were manifested as a normalization of malondialdehyde levels and glutathione levels which were all raised after CIS-induction. In addition, HS treatment resulted in a decrease of catalase, and superoxide dismutase activity. The combined effects of CIS and HS were also studied in two human lung cancer cell lines (A549 and H460). Treatment with HS (20 μg /mL) enhanced the cytotoxic activity of CIS both in A549 and H460 cell lines. Interestingly, HS increased CIS-induced apoptosis and oxidative stress more clearly in A549 cells indicating that HS extract in combination with CIS could increase the efficacy of CIS in the treatment of cancer.

Zanthoxylum bungeanum amides ameliorates nonalcoholic fatty liver via regulating gut microbiota and activating AMPK/Nrf2 signaling

Ethnopharmacological relevanceZanthoxylum bungeanum Maxim. (Rutaceae) is a known herbal medicine with various bioactivities, including anti-obesity, lipid-lowering, learning & memory improving and anti-diabetes, and amides in Z. bungeanum (AZB) are considered as the major active agents for its bioactivities. Aim of the studyThis research was carried out to uncover the anti-NAFL effect of AZB and its corresponding molecular mechanisms. MethodsThe central composite design-response surface methodology (CCD-RSM) was utilized to optimize the AZB extraction process, and the anti-NAFL effect of AZB was investigated on high fat diet (HFD) fed mice (HFD mice). The levels of ROS in liver tissues were determined using laser confocal microscopy with DCFH-DA probe staining, and anti-enzymes (such as HO-1, SOD, CAT & GSH-PX) and MDA in liver tissues were measured using commercial detecting kits. GC-MS was used to determine the short-chain fatty acids (SCFAs) contents in feces and blood of mice. 16S high-throughput sequencing, western blotting (WB) assay and immunofluorescence (IF) were used to explore the intestinal flora changes in mice and the potential mechanisms of AZB for treatment of NAFL. ResultsOur results showed AZB reduced body weight, alleviated liver pathological changes, reduced fat accumulation, and improved oxidative stress in HFD mice. In addition, we also found AZB improved OGTT and ITT, reduced TG, TC, LDL-C, whereas increased HDL-C in HFD mice. AZB increased total number of the species and interspecies kinship of gut microbiota and reduced the richness and diversity of gut microbiota in HFD mice. Moreover, AZB decreased the ratio of Firmicutes/Bacteroidota, whereas increased the abundance of Allobaculum, Bacteroides and Dubosiella in feces of HFD-fed mice. Furthermore, AZB increased the production of SCFAs, and up-regulated the phosphorylation of AMPK and increased the nuclear transcription of Nrf2 in liver of HFD mice. ConclusionCollectively, our results suggested AZB can improve NAFL, which could reduce body weight, reverse liver lesions and fat accumulation, improve oxidative stress in liver tissues of HFD mice. Furthermore, the mechanisms are related to increase of the abundance of high-producing bacteria for SCFAs (e.g. Allobaculum, Bacteroides and Dubosiella) to activate AMPK/Nrf2 signaling.

Oxidative Stress Caused by Lithium Exposure in the Carassius auratus (goldfish) Liver Tissue

Lithium is a therapeutic agent widely used in the treatment of some psychiatric disorders. The aim of this study was to investigate the effects lithium-induced oxidative stress in liver tissue. In this study, Carassius auratus fish was used as a model organism and total 20 control fish and 28 experimental fishes were divided 4 subgroups randomly. Lithium chloride at a concentration of 50 mg/L was added to the glass tank of the experimental group. Fish were placed in two separate glass tanks, 20 in the control group and 28 in the experimental group. Lithium chloride at a concentration of 50 mg/L was added to the glass tank, which is the experimental group. At the 24th, 48th, 72nd and 96th hours of the study, 5 samples from the control group and 7 samples from the experimental group were included in the study in four different time periods. At the end of the study, it was determined that the level of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and acetylcholinesterase(AchE) decreased in the group with lithium exposure, while the levels of Malondialdehyde (MDA) increased. It was determined that oxidative stress occurred in lithium exposure.

FRI-367 - The effect of the combination of metformin with propionic acid on the indicators of oxidative stress in liver tissue of rats with type 2 diabetes mellitus

FRI-367 - The effect of the combination of metformin with propionic acid on the indicators of oxidative stress in liver tissue of rats with type 2 diabetes mellitus

Oleanolic acid inhibits mercury chloride induced-liver ferroptosis by regulating ROS/iron overload

Mercury chloride can cause severe liver injury, which involves multiple mechanisms. Ferroptosis plays an important role in regulating the development and progression of liver pathology. Oleanolic acid (OA), a triterpenoid compound widely exists in fruits, has liver protective properties. In this study, we investigated the role of ferroptosis in mercury chloride-induced liver injury and the intervention effect of OA, and clarified the potential mechanism. We found that mercury chloride-induced oxidative stress in liver tissues and cells, leading to lipid peroxidation and iron overload, thereby reducing the expression levels of GPX4 and SLC7A11, and increasing the expression level of TRF1, OA pretreatment improved the changes of GPX4, SLC7A11 and TRF1 induced by mercury chloride, which were related to its inhibition of oxidative stress. Furthermore, We pretreated cells with OA, VC, and Fer-1, respectively and found that VC pretreatment reduced oxidative stress and significantly reversed the gene and protein expressions of GPX4, SLC7A11, and TRF1 in mercury chloride-exposed cells (P < 0.05, vs. HgCl2 group), however, the protein expression level of GPX4 in OA pre-treatment group was lower than that in VC pre-treatment group (P < 0.05). Fer-1 pretreatment decreased the level of iron ions in cells, increased the gene and protein expression levels of GPX4 and SLC7A11, and decreased the gene and protein expression levels of TRF1 (P < 0.05, vs. HgCl2 group), however, the protein expression levels of GPX4 and SLC7A11 in OA pre-treatment group were lower than those in Fer-1 pre-treatment group (P < 0.05). Moreover, vivo experiments also demonstrated that pre-treatment with OA, VC, and Fer-1 reversed the changes in gene expression levels of Nrf2 and SOD1, and protein expression of GPX4 induced by mercury chloride (P < 0.05, vs. HgCl2 group), meanwhile, the difference was not statistically significant among OA, VC, and Fer-1 pretreatment. The improvement effect of OA pretreatment on the change in TFR1 protein expression caused by mercury chloride was similar to that of Fer-1 and VC, however, the intervention effect of OA on SLC7A11 protein expression was not as good as Fer-1 and VC pre-treatment. To sum up, all these results suggest that ferroptosis is involved in mercury chloride-induced liver injury, OA pretreatment alleviated mercury chloride-induced ferroptosis by inhibiting ROS production and iron ion overload, and then alleviate the liver injury.

Microplastic Presence in the Digestive Tract of Pearly Razorfish Xyrichtys novacula Causes Oxidative Stress in Liver Tissue.

Plastic pollution in the oceans is a growing problem, with negative effects on exposed species and ecosystems. Xyrichtys novacula L. is a very important fish species both culturally and economically in the Balearic Islands. The aim of the present study was to detect and categorise the presence of microplastics (MPs) in the digestive tract of X. novacula, as well as the existence of oxidative stress in the liver. For this purpose, the fish were categorised into two groups based on the number of MPs observed in the digestive tracts: a group with no or low presence of MPs (0-3 items) and a group with a higher presence of MPs (4-28 items). MPs were found in 89% of the specimens analysed, with a dominance of fibre type and blue colour. Regarding the type of polymer, polycarbonate was the most abundant, followed by polypropylene and polyethylene. For the group with a greater presence of MPs, the activities of the antioxidant enzymes glutathione peroxidase and glutathione reductase, as well as the phase II detoxification enzyme glutathione s-transferase, were higher than the activities observed in fish with little to no presence of MPs. The activities of catalase and superoxide dismutase and the levels of malondialdehyde did not show significant differences between both groups. In conclusion, these results demonstrate the presence of MPs in the digestive tract of X. novacula and the existence of an antioxidant and detoxification response, mainly based on the glutathione-based enzymes.

High Fischer ratio oligopeptides from hard-shelled mussel: Preparation and hepatoprotective effect against acetaminophen-induced liver injury in mice

High Fischer ratio oligopeptides (HFOPs) have a variety of physiological activities, but there are few literatures reporting the hepatoprotective effects of HFOPs against acetaminophen (APAP)-induced liver injury. The objectives of this study were to establish the preparation process of HFOPs from hard-shelled mussel (Mytilus coruscus) (HFOPs-HM) and investigate the hepatoprotective effects and potential mechanisms of HFOPs-HM against APAP-induced liver injury in mice. Therefore, trypsin and papain were selected as the endo and exogenous proteases for preparing HFOPs-HM according to the degree of hydrolysis (DH) of hard-shelled mussel hydrolysates, and activated carbon of XHJ-200 displayed the best effect to remove aromatic amino acids according to the Fischer ratio (OD220/OD280) and its parameters were optimized as adsorption time of 3.0 h and solid-liquid ratio of 1:10. The HFOPs-HM's Fischer ratio and average molecular weight were 26.03 (>20) and 878.54 Da, respectively. Furthermore, a mice model of liver injury induced by APAP was established. HFOPs-HM could significantly improve liver index and histopathological features, decrease the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, increase the glutathione content and superoxide dismutase (SOD) and catalase (CAT) activities. Further research demonstrated that HFOPs-HM could alleviate liver oxidative stress in liver tissue via activating the Nrf2 pathway to initiate the intracellular antioxidant enzyme system. In addition, HFOPs-HM also suppressed liver inflammation by downregulating the secretion of TNF-α, IL-1β, and IL-6. Thus, HFOPs-HM could serve as an auxiliary functional dietary molecule applied in function products to alleviate drug-induced liver injury.

Therapeutic role of melatonin on acrylamide-induced hepatotoxicity in pinealectomized rats: Effects on oxidative stress, NF-κB signaling pathway, and hepatocellular proliferation.

Acrylamide (AA) is formed in some foods by the cooking process at high temperatures, and it could be a carcinogen in humans and rodents. The purpose of the current study was to reveal the possible protective effects of melatonin against AA-induced hepatic oxidative stress, hepatic inflammation, and hepatocellular proliferation in pinealectomized rats. Hence, the sham and pinealectomized rats were consecutively given AA alone (25mg/kg) or with melatonin (10mg/kg) for 21 days. Melatonin acts as an antioxidant, anti-inflammatory, and antiapoptotic agent and introduces as a therapeutic strategy for AA-induced hepatotoxicity. Melatonin supplementation reduced AA-caused liver damage by decreasing the serum AST, ALT, and ALP levels. Melatonin raised the activities of SOD and CAT and levels of GSH and suppressed hepatic inflammation (TNF-α) and hepatic oxidative stress in liver tissues. Moreover, histopathological alterations and the disturbances in immunohistochemical expression of NF-κB and Ki67 were improved after melatonin treatment in AA-induced hepatotoxicity. Overall, our results demonstrate that melatonin supplementation exhibits adequate hepatoprotective effects against hepatotoxicity of AA on pinealectomized rat liver architecture and the tissue function through the equilibration of oxidant/antioxidant status, the regulation of cell proliferation and the suppression of the release of proinflammatory cytokines.

Features of the influence of S-ethyl-4-aminobenzene thiosulfonate on some biochemical parameters of rat blood under the condition of Cr(VI) intoxication

Background. The main pathway of Cr(VI) cytotoxicity is activation of oxidative stress in cells of living organisms, resulting in an imbalance of blood biochemical para­me­ters. Our recent studies indicate that S-ethyl-4-aminobenzenethiosulfonate (ETS), which belongs to thiosulfonate compounds, is able to reduce intensity of Cr(VI)-induced oxidative stress in liver tissue of rats. It is known that oxidative stress induced by Cr(VI) causes liver and kidney tissue damage with a subsequent imbalance of blood biochemical parameters. Therefore, the aim of this study was to evaluate the potential ability of ETS to prevent Cr(VI)-induced disorders of some biochemical blood parameters, which are important biomarkers of Cr(VI) intoxication. Materials and Methods. The object of the research was the separate biochemical parameters of the blood of rats with Cr(VI)-induced oxidative stress after prior exposure to ETS. Two experimental groups of male Wistar rats were intoxicated once per day intraperitoneally with K2Cr2O7 dissolved in physiological saline solution for 7 or 14 days. Two other experimental groups were pretreated once per day intragastrically with ETS dissolved in oil before the period of 7 or 14-day K2Cr2O7 intoxication. We measured total protein, creatinine and urea level, as well as determined the activity of aminotransferases in the blood plasma of rats. Results. Intraperitoneal injection of K2Cr2O7 (dissolved in physiological saline solution at a dose of 2.5 mg Cr(VI)/kg body weight) for 7 and 14 days causes a decrease in total protein level and leads to elevation of plasma creatinine level and urea concentration. The activity of blood aminotransferases increases due to Cr(VI) toxicity. The 14-day exposure to ETS (dissolved in oil at a dose 100 mg/kg body weight) prior to the period of Cr(VI) intoxication is characterized by a smaller percentage increase in the level of crea­tinine, urea and activity of alanine aminotransferase (ALT) in the blood plasma of rats. Conclusion. Cr(VI)-induced toxicity causes an imbalance in biochemical blood parameters. Cr(VI) induces a total protein decrease and leads to an increase in the level of the studied biochemical parameters of blood plasma, which are markers of damage to the liver (aminotransferases) and kidneys (creatinine, urea). In contrast, exposure to ETS for 14 days prior to the period of Cr(VI) intoxication causes percentage decrease in creatinine, urea accumulation and percentage reduction of ALT hyper-activation in the blood of rats. However, the levels of creatinine, urea and ALT activity in this case remained significantly higher than those in the control group. In conclusion, pretreatment with ETS (100 mg/kg) for 2 weeks helps to reduce the level of Cr(VI)-induced disturbances of some blood biochemical parameters, but does not normalize them.

PS-B07-10: SUPEROXIDE DISMUTASE PROFILE OF LIVER TISSUE IN HYPERURICEMIA RATS AFTER DAILY CONSUMPTION OF COFFEE

Background: The elevation of serum uric acid may cause metabolic syndrome and increase systemic inflammation also oxidative stress which are the risk factors for liver disease. Recently, coffee as the most popular drink worldwide could promote antioxidant activity due to some anti-inflammatory effects of some polyphenolic compounds such as cafestol, kahweol, and diterpenes. This study aimed to analyze the profile of liver tissue superoxide dismutase (SOD) in hyperuricemia rats after daily consumption of coffee. Method: Four groups, each consisting of 6 rats (Rattus norvegicus), respectively were observed as 1) negative control group; 2) positive control group; 3) caffeinated coffee group; 4) decaffeinated coffee group. Hyperuricemia was conditioned by administering high purine intake into the 2nd until 4th group as much as 140 mg/200gr of weight. Coffee, which is caffeinated and decaffeinated was given to the third and the fourth group respectively with doses 144 mg/200gr of weight. SOD of liver tissue was measured after 30 days of treatment. Result: In hyperuricemia rats, daily consumption of coffee shows higher liver SOD levels compared to a positive control group. The average (+SD) of liver SOD each group respectively 79.51(+3.06); 32.24(+3.53); 53.28(+4.49); and 68.03(+4.72). Numeric comparative hypothetic test using one-way ANOVA shows the difference mean between each group was statistically significant (95%CI; p &lt; 0.05). Conclusion: Daily consumption of both caffeinated and decaffeinated coffee may reduce oxidative stress in liver tissue of hyperuricemia rats.