Lipid Peroxidation In Liver Tissue Research Articles

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2mL/day sc. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; H-homocysteine 0.45µmol/g b.w. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; CPA-saline 0.2mL/day sc. 2×/day for 14days + aerobic treadmill training for 28days; and HPA-homocysteine 0.45µmol/gb.w. 2×/day for 14days + aerobic treadmill training for 28days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Iron Overload Induces Hepatic Ferroptosis and Insulin Resistance by Inhibiting the Jak2/stat3/slc7a11 Signaling Pathway.

Recent studies showed that patients with iron overload had increased risk of insulin resistance or diabetes. Ferroptosis is a new type of cell death mainly caused by iron-dependent oxidative damage. In the present study, we investigated potential mechanisms of iron overload induced hepatic ferroptosis and insulin resistance through in vivo and in vitro experiments. In vivo, the mice models of iron overload were established by intraperitoneal injection of iron dextran. The changes of body weight, serum ferritin and blood glucose were measured. Hematoxylin-eosin (HE) and Perl's stainings were used to observe the pathological changes and iron deposition in the liver of mice. In vitro, HepG2 cells were treated with ferric ammonium citrate (FAC, 9 mmol/L, 24 h) to establish the cell models of iron overload. The labile iron pool, cell viability, glucose consumption and glycogen contents were measured. The ultrastructure of mitochondria was observed by transmission electron microscope (TEM). The malondialdehyde (MDA) and glutathione (GSH) kits were used to detect lipid peroxidation in liver tissues of mice and HepG2 cells. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of ferroptosis factors and JAK2/STAT3 signaling pathway. In this study, we used the iron chelator deferasirox in mice and HepG2 cells. Iron overload caused weight loss, elevated serum ferritin, fasting blood glucose, fasting insulin, HOMA-IR, impaired glucose tolerance, and decreased insulin sensitivity in mice. HE staining and Perls staining showed clumps of iron deposition in the liver of iron overload mice. Iron overload could reduce the glucose consumption, increase MDA contents of HepG2 cells, while reduce glycogen and GSH contents in liver tissues of mice and HepG2 cells. TEM showed deletion of mitochondrial ridge and rupture of outer membrane in HepG2 cells with iron overload. Iron chelator deferasirox could significantly improve the above indicators, which might be related to the activation of JAK2/STAT3/SLC7A11 signaling pathway and hepatic ferroptosis. Iron overload could induce hepatic ferroptosis and insulin resistance by inhibiting the JAK2/STAT3/SLC7A11 signaling pathway, and the iron chelator deferasirox might improve hepatic insulin resistance induced by iron overload.

Therapeutic potentials of N-acetylcysteine immobilized polyrhodanine nanoparticles toward acetaminophen-induced acute hepatotoxicity in rat.

N-acetylcysteine (NAC) is a recommended drug for treating acetaminophen (APAP) intoxication. Due to NAC's low bioavailability, this study aimed to use polyrhodanine (PR) nanoparticles (NPs) as a drug carrier to improve the effectiveness of NAC. After preparation and characterization of NAC loaded on PR, 30 rats were randomly divided into five groups of six. The first group (control) received normal saline. Groups 2-5 were treated with normal saline, PR, NAC, and NAC loaded on PR, respectively. The treatments were started 4 h after oral administration of APAP (2000 mg kg-1 ). After 48 h, the animals were anesthetized, and liver function indices and oxidative stress were measured in tissue and serum samples. The APAP administration can increase aminotransferases and alkaline phosphatase enzymes in serum, decreasing the total antioxidant capacity and thiol groups and increasing lipid peroxidation in liver tissue. Administration of PR-NAC could effectively improve the level of serum-hepatic enzymes, total antioxidant capacity and thiol groups, lipid peroxidation, and pathological changes in liver tissue in animals poisoned with APAP. PR-NAC has a significant therapeutic effect on preventing acute hepatotoxicity caused by APAP, and its effectiveness can be associated with an improvement in the oxidant/antioxidant balance of liver tissue.

New Dipterocarpol-Based Molecules with α-Glucosidase Inhibitory and Hypoglycemic Activity.

Dammarane triterpenoids are affordable and bioactive natural metabolites with great structural potential, which makes them attractive sources for drug development. The aim of the study was to investigate the potency of new dipterocarpol derivatives for the treatment of diabetes. Two dammaranes (dipterocarpol and its 20(24)-diene derivative) were modified by a Claisen-Schmidt aldol condensation to afford C2(E)-arylidenes in good yields. The majority of the synthesized compounds exhibited an excellent-to-moderate inhibitory effect toward α-glucosidase (from S. saccharomyces), among them eight compounds showed IC50 values less than 10 μM. 3-Oxo-dammarane-2(E)-benzylidenes (holding p-hydroxy- 3 l and p-carbonyl- 3 m substituents) demonstrated the most potent α-glucosidase inhibition with IC50 0.753 and 0.204 μM, being 232- and 857-times more active than acarbose (IC50 174.90 μM), and a high level of NO inhibition in Raw 264.7 cells with IC50 of 1.75 and 4.57 μM, respectively. An in vivo testing of compound 3 m (in a dose of 20 mg/kg) on a model of streptozotocin-induced T1DM in rats showed a pronounced hypoglycemic activity, the ability to reduce effectively the processes of lipid peroxidation in liver tissue and decrease the excretion of glucose and pyruvic acid in the urine. Compound 3 m reduced the death of diabetic rats and preserved their motor activity.

PROSPECTS OF HEPATOPROTECTIVE EFFECT OF SESQUITERPENE LACTONE ABSINTIN

Liver and gallbladder diseases are among the most common in the world today. Liver disorders occupy one of the most important places in the pic-ture of general human pathology, having a fairly high risk of developing adverse complications. Preparations and biologically active additives based on Artemisia absinthium and the components extracted from it have recently become very popular. The group of sesquiterpene lactones is of the greatest interest to researchers. The object of this review article is to analyze domestic and foreign publications showing the pharmacological activity and pro-spects of using absinthin, which is part of the group of sesquiterpene lactones of A. absinthium, as a hepatoprotector. An analysis of the literature re-vealed that absinthin has an antitoxic effect, reduces lipid peroxidation in liver tissues and restores the activity of protective antioxidant enzymes su-peroxide dismutase (SOD) and glutathione peroxidase (GPx) to a normal level. The generalization of literature data showing the pharmacological effect of the substance indicates the ability of absinthin to reduce the level of toxic effects of fatty acids and cholesterol on hepatocytes. It was also revealed that absinthin is able to have an antiproliferative effect on human adenocarcinoma cells. The positive effect observed when using absinthin character-izes the prospects of its practical application as a drug or biologically active additive with hepatoprotective and antitumor effect.

Стан прооксидантної та антиоксидантної систем організму щурів за умов однократної дії деяких метильних похідних N-оксид піридину – Івіну і Потейтіну

АBSTRACT. Previously, it was shown that pyridine N-oxide based plant growth regulators (PGR) Ivin and Poteitin when combined with pesticides reduce the acute and subchronic toxicity of pesticides for mammals, have a hepatoprotective effect, contribute to the reduction of mutagenic activity, in particular, of Cyclophosphane and Dioxidin cytostatics (Vasetska O.P., 2017, Vasetska O.P. et al., 2020, 2021). It is possible that a wide range of their biological effects may be associated with the activation of the body’s protective systems, in particular the antioxidant system. The effect of these PGRs on the state of the pro-oxidant and antioxidant systems is not sufficiently clarified. Therefore, an important issue for preventive toxicology is the study of the nature of the effect of PGR on the state of the body’s pro-oxidant and antioxidant systems, which will contribute to the development of preventive measures to preclude acute and chronic intoxications with pesticides. Aim. To find out the state of the body’s pro-oxidant and antioxidant systems under a single oral exposure to some plant growth regulators –pyridine N-oxide methyl derivatives. Materials and Methods. For the aim of this research we used PGR 2.6-dimethyl- pyridine N-oxide (Ivin) and a complex of 2.6- dimethylpyridine-N-oxide with succinic acid (Poteitin). PGR in the form of an aqueous solution was administered to male Wistar Han rats orally with a probe: Ivin at doses of 650 mg/kg (1/2 LD50) and 13 mg/kg (1/100 LD50), Poteitin – at doses of 1150 mg/kg (1/2 LD50) and 23 mg/kg (1/100 LD50). The influence of Ivin and Poteitin on the lipid peroxidation (LPO) and the antioxidant system under a single oral exposure to the body of male rats was determined on days 1, 3, and 7. LPO in liver tissues was determined by the content of malondialdehyde (MDA), diene conjugates (DC), ketodienes (KD), conjugated trienes (CT) and Schiff bases (SB). MDA level was determined by the reaction with 2-thiobarbituric acid, DC, KD, CT, and SB in liver tissues – by the extraction-spectrophotometric method. The antioxidant status of the body was assessed by the activity of the catalase enzymes (CAT), glutathione peroxidase (GP), glutathione reductase (GR), the content of reduced glutathione (GSH) and total antioxidant activity (AOA). The results of the research were estimated by standard methods of variational statistics according to Student’s t-test criterion. Results. It was established that Ivin in the researched doses in the heptane fraction reduces the LPO intensity (containing MDA, DC, SB) in the liver tissues of rats, in the isopropanol fraction – DC; increases the activity of catalase and total AOA in blood serum. Poteitin in the tested doses in the heptane fraction reduces the formation of lipid products (containing MDA, DC, KD and CT) in the liver tissues of rats, in the isopropanol fraction – DC; increases the activity of catalase and the content of GSH, total AOA. Both substances do not disrupt the glutathione system. Compared to Ivin, Poteitin has a more pronounced effect on the intensity of LPO and the activity of the antioxidant system. Conclusions. 1. Plant growth regulators Ivin and Poteitin, at a single exposure to the body of male rats in doses corresponding to 1/2 and 1/100 LD50, reduce pro-oxidant activity, do not disrupt the glutathione system, increase the activity of the antioxidant system. 2. Increase in the activity of the antioxidant system and inhibition of the intensity of lipid peroxidation processes both under the influence of Ivin and Poteitin are aimed at adapting the body to the chemical factor. 3. Activation of the antioxidant system together with a decrease in the intensity of LPO can be one of the mechanisms of protection of the body from the toxic effects of pesticides when they are simultaneously introduced into the body with plant growth regulators based on methyl derivatives of pyridine N-oxide. Key words: plant growth regulators, Ivin, Poteitin, prooxidant and antioxidant systems.

Effect of Aqueous Turmeric Extract on Lipid Peroxidation and Activity of Antioxidant Enzymes in Liver Tissue of Chick Embryo Treated with silver nanoParticles

Turmeric extract has antioxidant, antibacterial, antifungal, antiviral, and anti-inflammatory effects, and in addition, curcumin present in turmeric extract can be a powerful protective factor against biochemical changes and cellular oxidative damages. In order to investigate the effect of turmeric aqueous extract on lipid peroxidation and the activity of antioxidant enzymes in the liver tissue of chick embryos treated with silver nanoparticles, 45 race Ross 308 fertilized eggs were randomly divided into control groups (single injection of 0.5 ml saline solution) and 4 treated groups. On the 10th day of incubation, treated groups of 1, 2, 3 and 4 received silver nanoparticles (a single injection of 0.5 ml silver nanoparticles, 200 ppm and 60 nm). On the 12th day of incubation, treated groups of 2, 3 and 4 received turmeric aqueous extract with concentrations of 100, 200 and 300 μg/ml (single injection of 0.5 ml turmeric aqueous extract). The injection was done in the amnion sac embryos. On the 20th day of incubation, the concentration of malondialdehyde and the activity of superoxide dismutase, glutathione peroxidase and catalase enzymes in liver tissue were measured by ELISA method. Statistical analysis was carried out by using one-way ANOVA and post-hoc Tukey tests (p<0.05). Compared to treated group 1, the tissue concentration of superoxide dismutase, glutathione peroxidase and catalase in treated groups 2, 3 and 4 significantly increased and the tissue concentration of malondialdehyde decreased significantly (p<0.05). Dose-dependent injection of turmeric aqueous extract dreduces the toxicity caused by silver nanoparticle and reduces oxidative stress and lipid peroxidation in liver tissue of chick embryos.

The Effect of Swimming and Resveratrol on Antioxidant Markers and Lipid Peroxidation Index in Liver Tissue

Background Aging is associated with metabolic disorders. Although the beneficial effects of exercise and resveratrol consumption in the health of the elderly has been reported, the combined effect of intermittent swimming and resveratrol consumption on the antioxidant system in liver tissue is not clear yet. Objective This study aims to investigate the combined effect of intermittent swimming and resveratrol consumption on the expression of superoxide dismutases (SOD), glutathione peroxidase (GPx), and Malondialdehyde (MDA) in the liver tissue of older rats. Methods In this experimental study, 32 elder rats were divided into four groups: control, swimming, resveratrol and swimming+resveratrol. The resveratrol (100 mg) dissolved in 1% methylcellulose was administrated daily by gavage. The swimming was performed at three sessions per week. The GPx and SOD expression levels were measured by real-time polymerase chain reaction method, and the MDA level was measured by ELISA method. Results The GPx level in the swimming+resveratrol group were significantly higher than in the control (P=0.001), resveratrol (P=0.04) and swimming (P=0.002) groups. MDA levels in the resveratrol (P=0.001), swimming (P=0.001) and swimming+resveratrol (P=0.001) groups were significantly lower than in the control group; in the swimming+resveratrol group, it was significantly lower than the resveratrol (P=0.001) and swimming (P=0.009) groups. Conclusion It seems that intermittent swimming and resveratrol consumption have favorable effects on improving the antioxidant defense system and lipid peroxidation in liver tissue. Therefore, it is recommended to use intermittent swimming and resveratrol to prevent liver damage in the elderly.

Ameliorative impact of herbal formulation -Majoon-Dabeed-ul-ward and Sharbat-e-Deenar against CCl4 induced liver toxicity via regulation of antioxidant enzymes and oxidative stress.

Polyherbal Unani formulations have been used in the treatment of liver diseases for a long time. (Ibrahim M, Khaja MN, Aara A, Khan AA, Habeeb MA, Devi YP, Narasu ML, Habibullah CM. Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: in vitro and in vivo studies. World J Gastroenterol. 2008:14:2566-2571.) The aim of the present study was to investigate comparative hepatoprotective potential of Majoon-e-Dabeed-ul-ward (MD) and Sharbat-e-Deenar (SD) against CCl4 induced subchronic hepatic toxicity. In vivo study, albino rats were divided into 5 groups. Group I was control; Group II was experimental control treated with CCl4 (0.15mL/kg, i.p. for 21days); Groups III-IV treated with SD (2mL/kg, p.o.) and MD (1,000mg/kg, p.o.) for 5days following CCl4 intoxication as in group 2 respectively; and Group V was positive control treated with silymarin (50mg/kg, p.o.). In vitro hepatoprotective activity of SD and MD (25, 50, and 100μg/mL) was assessed by SRB assay and flow cytometry analysis. CCl4 exposure significantly elevated the release of hepatic enzymes i.e. AST, ALT, LDH, and SALP in serum and lipid peroxidation in liver tissue which all these parameters were reversed after SD and MD administration. Therapy for 5days also normalized the levels of antioxidant enzymes i.e. catalase, SOD, GPx, GR, tissue GSH, and aniline hydroxylase in CCl4 treated group. DNA damage and histological alterations caused by CCl4 were restored towards normal group. In vitro study showed protective effect of SD and MD against CCl4 treated HepG2 cell lines and rat hepatocytes. The results suggested that MD has a significant hepatoprotective potential and regulatory effect on oxidative stress than SD against CCl4 induced hepatotoxicity, and that this effect may be related to its antioxidant activity.

Hepatoprotective activity of Picrorhiza kurroa and Berberis lycium is mediated by inhibition of COX-2 and TGF-β expression in lantadenes-induced sub-chronic toxicity in guinea pigs

BackgroundThe toxicity of Lantana camara weed is common in grazing livestock throughout the world. Specific treatment for the toxicity is lacking. However, herbal plants could be investigated for their effectiveness in inhibiting hepatic damage caused by lantadenes of L. camara. Therefore, the extracts Berberis lycium and Picrorhiza kurroa, which are known to exhibit multiple useful effects were assessed for their hepatoprotective action in sub-chronic lantadene toxicity. PurposeThe focus of the study was to investigate the molecular pathogenesis of sub-chronic lantadene toxicity and, the mechanism of hepatoprotection by freeze-dried methanolic extracts of the Berberis lycium root bark and Picrorhiza kurroa rhizome in lantadenes-induced sub-chronic hepatopathy in guinea pig laboratory animal model. MethodsIsolation of lantadenes from L. camara leaves, followed by its characterization and quantification by UPLC-MS method was done. The methanolic extracts of ameliorating plant parts (root bark of B. lycium, rhizome of P. kurroa) were prepared and quantification of berberine and picroside was carried out. The in vivo sub-chronic toxicity and amelioration experiment in guinea pigs was conducted for 90 days by distributing them into 7 groups with 6 animals in each group. At the end of the experiment, serum biochemical analysis, oxidation stress levels in the liver and kidneys were determined. Gross pathology and microscopic observations in different organs, Masson’s trichome staining for fibrous collagenous tissue deposition assessment, and immunohistochemical expression of the TGF-β antigen in the liver of animals were done. The effect of lantadenes on pro-inflammatory cytokines and the level of α-smooth muscle actin in the liver was estimated by real-time RT-PCR and ELISA, respectively. ResultsSub-chronic lantadene intoxication increased serum ALT, AST, ALP, bilirubin, creatinine, total proteins and lipid peroxidation in liver tissue; decreased catalase, superoxide dismutase and reduced glutathione activity in liver tissue; caused hepatic necrosis with bile duct proliferation and TGF-β antigen expression in the periportal regions; upregulated the IL-1β, IL-6, TGF-β, and COX-2 pro-inflammatory cytokine gene expression and increased the titre of α-SMA in the liver. The P. kurroa extract at 200 mg/kg bw and B. lycium extract at 200 mg/kg bw produced favourable effects against lantadenes-induced hepatic toxicity and significantly reversed these changes to near normal. ConclusionsP. kurroa and B. lycium extracts at 200 mg/kg bw can be used to ameliorate the hepatotoxicity produced by sub-chronic exposure to lantadenes. The findings of the molecular pathogenesis of sub-chronic lantadene toxicity and its amelioration in guinea pig laboratory animal model are novel. Further investigations are needed to study the in-depth mechanism of hepatoprotection of P. kurroa and B. lycium in lantana intoxicated grazing (host) animals.

Effects of ketogenic and western diets on proliferation, vasculogenesis and oxidative stress in the liver

In this study, it was aimed to investigate the effects of different diets on lipid peroxidation, antioxidants, proliferation and vasculogenesis in liver tissue. BALBC female rats (21) were divided as the group fed with standard chow (SC), the group fed with a ketogenic diet (KD) and the group fed with western diet (WD). The rats were fed with tap water and a rat diet specially prepared according to the determined diets for four weeks. Liver tissue oxidative damage, proliferation and vasculogenesis were evaluated using spectrophotometric and immunohistopathological methods. At the end of the experiment, it was found that the highest weight gain was in the WD group and the least weight gain was in the KD group. The mean body weight of the WD group was statistically significantly higher compared to the SC and KD groups (p<0.05). MDA levels were found to be lower in the KD group compared to the SC and WD groups. GSH and CAT levels were higher in the KD group compared to the SC and WD groups. In IHC evaluation results, it was seen that Ki-67 percentage in the KD group increased compared to the WD and SC groups (p = 0.000), VEGF was close to each other in all three groups and there was no significant difference in the comparisons between groups (p>0.05). These results revealed that ketogenic diet prevents tissue damage by decreasing lipid peroxidation in liver tissue as well as inducing cellular proliferation and vasculogenesis.

Hepatoprotective effect of ferulic acid and/or low doses of γ-irradiation against cisplatin-induced liver injury in rats.

The therapeutic efficacy of cisplatin (CIS) is limited owing to its hepatotoxic side effects. The current study aimed to investigate the protective impact of ferulic acid (FA) and low-doses of γ-irradiation (LDR) against CIS-prompted hepatotoxicity in rats. Adult male Swiss albino rats were divided into eight groups: untreated group; FA, LDR, and CIS treated groups; and combinations of one or more of the above treatments. Post-treatment analyses included measuring redox markers like SOD and CAT activity, NO free radical content, and lipid peroxidation in liver tissue. Serum aminotransferase activities were also determined. Additionally, gene transcript levels of liver NF-ҡB-P65, caspase-1, COX-2, and IL-1β were quantified. Moreover, immunohistochemistry for caspase-3 and histopathological examinations were estimated in liver tissue. Our findings revealed increased levels of oxidative stress along with a significant reduction in anti-oxidative responses and a significant increase in serum aminotransferase activities in the CIS-intoxicated group. A similar increase was also observed in COX-2 and IL-1β transcript levels and caspase-3 enzyme activity, besides a decrease in transcript levels of NF-ҡB-p65 and caspase-1, indicating an overall inflammatory trend and an increase in the apoptotic shift. The co-administration of FA and/or treatment with LDR has ameliorated the hepatotoxic effect induced by CIS. The histopathological investigation of liver tissues confirmed this ameliorating action of these adjuvant therapies against CIS toxicity. In conclusion, it is plausible to suggest that the hepatoprotective effects of co-administration of FA and/or LDR against CIS-induced hepatotoxicity are attributed to the possession of anti-oxidative, anti-inflammatory, and anti-apoptotic capabilities.

Benchmark dose and the adverse effects of exposure to pendimethalin at low dose in female rats.

Pendimethalin (PND) is a dinitroaniline herbicide widely used to control broadleaf and annual grasses. Although the acute oral toxicity of PND is >5g/kg b.wt. in humans (LD50 for rats >5000 g/kg b.wt.), it has been classified as a possible human carcinogen. It is still used in agriculture so agricultural workers and their families, as well as consumers, can be exposed to this herbicide. The present study is the first report investigating the dose-response effect using the benchmark dose (BMD) and the adverse effects of exposure to PND at low dose via apoptosis responses linked to the expression of tumour necrosis factor-α (TNF-α), FAS and BAX proteins; oxidative stress; and DNA and liver damage in female rats. The rats were exposed to PND via drinking water at doses equivalent to no-observed-adverse-effect level (NOAEL = 100 mg/kg b.wt.), 200 and 400 mg/kg b.wt. for 28 days. PND caused the overexpression of TNF-α, FAS and BAX; increased the levels of serum liver biomarkers; and increased oxidative stress in the liver and erythrocytes. Furthermore, it induced DNA and liver damage in a dose-dependent manner. The BMD showed that serum alkaline phosphatase (ALP) and total antioxidant capacity (78.4 and 30.1mg/kg b.wt./day, respectively), lipid peroxidation in liver tissue (30.9mg/kg b.wt./day), catalase in erythrocytes (14.0mg/kg b.wt./day) and FAS expression in liver tissue (6.89 mg/kg b.wt./day) were highly sensitive biomarkers of PND toxicity. Our findings suggest the generation of reactive oxygen species as a possible mechanism of PND-induced gene overexpression of tumour necrosis factor-α (TNF-α), FAS and BAX proteins, oxidative stress and DNA and liver damage in female rats.

In vivo effects of exposure to Golden trumpet Handroanthus chrysotrichus in mice.

The Golden trumpet Handroanthus chrysotrichus is a tree that presents beneficial health properties against various diseases. Thus, this study aims to verify the toxicity of H. chrysotrichus bark extract, observing the effects of exposure to this extract in mice. For this, mice were separated in groups: saline (sterile solution .9%); H. chrysotrichus crude extract (HCCE) 10; HCCE 50, and HCCE 100mg. kg-1 (p.o.). We analyzed HCCE effects on acute (single exposure) and subchronic protocol (14 days exposure). After both exposures, acute, and subchronic, we collected samples from blood, brain, liver, and kidney tissues for biochemical evaluation. In addition, after subchronic exposure, we performed behavioral tests. Acute exposure caused an increase of lipid peroxidation in liver tissue. Moreover, we observed a significant carbonyl increase in liver and brain tissues from HCCE 50mg. kg-1. Kidneys presented carbonyl increase in mice treated with the highest concentration. Besides, creatinine increased in the group of the acute exposure at HCCE 100mg. kg-1. Total leukocyte count decreased in all concentrations tested. Sub-chronic exposure at HCCE 100mg. kg-1 caused a decrease in the number of crossing and an increase in its self-grooming frequency in the open field test. In this exposure, the brain and liver had a significant increase in carbonyl levels in all concentrations. We concluded that H. chrysotrichus cause behavioral and biochemical alterations in mice. HCCE primary targets seem to be the liver, kidneys, and white cells.

Effects of ketogenic and western diets on proliferation, vasculogenesis and oxidative stress in the liver

In this study, it was aimed to investigate the effects of different diets on lipid peroxidation, antioxidants, proliferation and vasculogenesis in liver tissue. BALBC female rats (21) were divided as the group fed with standard chow (SC), the group fed with a ketogenic diet (KD) and the group fed with western diet (WD). The rats were fed with tap water and a rat diet specially prepared according to the determined diets for 4 weeks. Liver tissue oxidative damage, proliferation and vasculogenesis were evaluated using spectrophotometric and immunohistopathological methods. At the end of the experiment, it was found that the highest weight gain was in the WD group and the least weight gain was in the KD group. The mean body weight of the WD group was statistically significantly higher compared to the SC and KD groups (p<0.05). MDA levels were found to be lower in the KD group compared to the SC and WD groups. GSH and CAT levels were higher in the KD group compared to the SC and WD groups. In IHC evaluation results, it was seen that Ki-67 percentage in the KD group increased compared to the WD and SC groups (p = 0.000), VEGF was close to each other in all three groups and there was no significant difference in the comparisons between groups (p>0.05). These results revealed that ketogenic diet prevents tissue damage by decreasing lipid peroxidation in liver tissue as well as inducing cellular proliferation and vasculogenesis.

P-Coumaric acid alleviates adriamycin-induced hepatotoxicity in rats

Objective: To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats. Methods: The rats were divided into 4 groups. The control group received solvent; the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days; the adriamycin group was administered with a single dose of adriamycin (15 mg/kg, i.p.), and the p-coumaric acid + adriamycin group was given p-coumaric acid five days before adriamycin administration. Twenty-four hours after the last administration, blood samples were collected for biochemical analysis, and liver tissues were removed for histopathological and immunohistochemistrical studies. Moreover, the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in liver tissue were measured. Results: Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase, alanine transaminase, aspartate transaminase, total bilirubin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin. p-Coumaric acid also raised the levels of glutathione peroxidase, superoxide dismutase, and catalase, as well as decreased lipid peroxidation in liver tissue and hepatic IL- 1β expression. Additionally, histopathological study confirmed the protective effect of p-coumaric acid against liver damage. Conclusions: p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.

An Evaluation of Effects of Black Grape and Ginger Extracts on Hematological Alteration and Lipid Peroxidation of Hepatocyte in Irradiated Albino Mice

Introduction: Exposure to ionizing radiation can trigger adverse biological effects on healthy tissues, such as causing hematological toxicity and potential injury to different organs. Ionizing radiation has sufficient energy to liberate electrons from atoms leaving them with unpaired electrons; hence ionizing them and producing free radicals. In the current study, the risk of exposing to 6 Gy x-irradiation on alteration of some hematological parameters and liver tissue lipid peroxidation activity in albino mice in the presence and absence of black grape and ginger extracts as antioxidants have been investigated. Material and Methods: Albino mice were exposed to 6 Gy wholebody xirradiation in the absence and presence of black grape and ginger extracts (10mL/Kg). Results: The results of the present study showed a significant decrease in mice red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin, following the exposure to 6 Gy x-irradiation (P≤0.05), while all the mentioned parameters were relatively shifted toward the normal values in the mice that received black grape and ginger extracts as a treatment prior to the radiation. Accordingly, our results demonstrated a noticeable increase in the malondialdehyde analysis (MDA) level in the 6 Gy group, while a slight depletion in the MDA level was observed in the group of mice that received black grape and ginger extracts, compared to that of the control group. Conclusion: the administration of black grape and ginger extracts prior to irradiation may protect the mice from excess hepatocyte lipid peroxidation and alteration of hematological parameters.

Inhibition of poly(ADP-ribose)polymerase contributes to the reduction of oxidative stress in murine liver under the conditions of experimental endotoxemia

The aim of the work is to investigate the effect of the enzyme poly(ADP-ribose)polymerase 1 (PARP-1) inhibitor, 4-hydroxyquinazoline (4-HQN), on the state of the pro- and antioxidant system of murine liver, under the conditions of lipopolysaccharide (LPS) induced inflammation. Materials and methods. Systemic endotoxemia was induced by the administration of LPS ( E. coli 0111:B4) at a dose of 3 mg/kg intraperitoneally (IP). A solution of 4-HQN was applied IP at a dose of 100 mg/kg an hour before LPS administration. The processes of lipid peroxidation (LPO) have been evaluated by the content of the end products of LPO in liver tissue by their reaction with thiobarbituric acid (TBA). The concentration of reduced glutathione (GSH) in liver was determined by Ellman's spectrophotometric method. The level of ceruloplasmin (CP) in serum was measured by colorimetric method of Ravin using a test kit (JSC Reagent, Ukraine) in accordance with the manufacturer’s instructions and expressed in mg/l. Results . It was established that 24 hours after LPS administration the content of TBA-reactive substances (TBARS) in liver tissue significantly increased, that indicates intensification of POL. The level of GSH and the activity of CP in serum significantly decreased under the conditions of LPS action. The use of the inhibitor PARP-1, 4-HQN, during endotoxemia resulted in 1.7-fold decrease in the amount of TBARS in liver tissue (P < 0.05 compared with LPS) and increased significantly the GSH content (2.9-fold, P < 0.05) and the CP (1.2-fold, P < 0.05). Conclusions . The data obtained using murine model of endotoxemia indicate the involvement of PARP-1 in intensification of POL. Pharmacological inhibition of this enzyme contributed to the reduction of oxidative stress in murine liver and improved the state of antioxidant protection of the body, that is, it had a pronounced protective effect during endotoxemia.

Betulin attenuated liver damage by prevention of hepatic mitochondrial dysfunction in rats with alcoholic steatohepatitis.

Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4g/kg, intragastric) for 8weeks. The treatment with betulin (50 and 100mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition.

Chemical Composition and Antioxidant Properties of Essential Oils from Peppermint, Native Spearmint and Scotch Spearmint.

Natural antioxidants have drawn growing interest for use in animal feed and the food industry. In the current study, essential oils (EOs) obtained from hydrodistillation of three mentha species, including Mentha piperita (peppermint), Mentha spicata (native spearmint) and Mentha gracilis (Scotch spearmint), harvested in the Midwest region in the United States, were analyzed for their chemical composition using gas chromatography-mass spectrometry, and their antioxidant properties were assessed through chemical assays, in vitro cell culture modeling and in Caenorhabditis elegans (C. elegans). The activity of ferric iron reduction and free-radical scavenging capacity were assessed through chemical-based assays, including the reducing power assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and Trolox equivalent antioxidant capacity assay (TEAC). Subsequently, the capacity of EOs to mitigate lipid peroxidation was analyzed at various doses using fresh liver homogenates from pigs. A porcine jejunum epithelial cell line (IPEC-J2) was employed as in vitro model to study the cellular antioxidant activity of the mint EOs. Finally, the effectiveness of mint EOs to alleviate acute systemic oxidative damage were evaluated in vivo using C. elegans. Data were analyzed by the MIXED procedure of SAS. Contrast statement was performed to assess linear or quadratic effects of mint EOs given at various doses. All three EOs are mostly composed of monoterpenes and their derivatives (76–90%), but differed in the major compounds, which are menthol and menthone (50%) in peppermint EO and carvone (70%) in spearmint EOs. Three mint EOs demonstrated prominent radical scavenging and Fe3+ reducing activity in chemical-based assays. In comparison with native and Scotch spearmint EOs, peppermint EO had the lowest (p < 0.05) half maximal effective concentration (EC50) in DPPH and TEAC assays and higher efficacy in the reducing power assay. All three EOs exhibited equivalent activity in mitigation of chemical-induced lipid peroxidation in liver tissues in a dose-dependent manner (linear, p < 0.001). The maximal cellular antioxidant activity (CAA) was observed at 5 µg/mL for peppermint, and 100 µg/mL for native and Scotch spearmint EOs. The addition of 25 µg/mL of both spearmint EOs increased (p < 0.05) cellular concentrations of glutathione in H2O2-treated IPEC-J2 cells, suggesting enhanced endogenous antioxidant defense. Supplementation of 100 µg/mL of peppermint or Scotch spearmint EO significantly increased (p < 0.05) the survival rate of C. elegans in response to H2O2-induced oxidative stress. The protective effect is comparable to that of supplementation of 10 µg/mL of ascorbic acid. However native spearmint EO failed to reduce the death rate within the same supplementation dose (10–200 μg/mL).