Lipid Peroxidation In Liver Of Mice Research Articles

Antioxidant activities and inhibitory effect of Taraxacum officinale, Cichorium intybus and Lectuca sativa on prooxidant induced lipid peroxidation in mice liver

Antioxidant activities and inhibitory effect of Taraxacum officinale, Cichorium intybus and Lectuca sativa on prooxidant induced lipid peroxidation in mice liver

Protective effect of rutaecarpine against t-BHP-induced hepatotoxicity by upregulating antioxidant enzymes via the CaMKII-Akt and Nrf2/ARE pathways

Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, has been shown to have cytoprotective potential, but the molecular mechanism underlying this activity remains unclear. Our study was designed to investigate the cytoprotective effect of rutaecarpine against tert-butyl hydroperoxide (t-BHP) and to elucidate its action mechanism of action of rutaecarpine in a cultured HepG2 cell line and in mouse liver. Rutaecarpine decreased t-BHP–induced reactive oxygen species (ROS) production, cytotoxicity, and apoptosis in HepG2 cells. Pretreatment with rutaecarpine prior to the injection of t-BHP significantly prevented the increase in serum levels of AST, ALT, and lipid peroxidation in mice liver. It increased the transcriptional activity of NF-E2–related factor 2 (Nrf2) as well as the products of the Nrf2 target genes hemeoxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutamate cysteine ligase (GCL). Moreover, rutaecarpine also enhanced the phosphorylation of Akt and Ca2+/calmodulin-dependent protein kinase-II (CaMKII). The pharmaceutical inhibitors, such as KN-93 (CaMKII inhibitor) and LY294002 (Akt inhibitor) suppressed rutaecarpine-induced HO-1 expression and cytoprotection. Our findings identify the CaMKII-PI3K/Akt-Nrf2 cascade as an antioxidant pathway mediating rutaecarpine signaling and leading to HO-1 expression in hepatocytes.

Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function

Dicranostiga Leptodu (Maxim.) fedde (DLF), a poppy plant, has been reported have many benefits and medicinal properties, including free radicals scavenging and detoxifying. However, the protective effect of DLF extracts against carbon tetrachloride (CCl4)-induced damage in mice liver has not been elucidated. Here, we demonstrated that DLF extracts attenuated CCl4-induced liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function. In this study, the mice liver damage evoked by CCl4 was marked by morphology changes, significant rise in lipid peroxidation, as well as alterations of mitochondrial respiratory function. Interestingly, pretreatment with DLF extracts attenuated CCl4-induced morphological damage and increasing of lipid peroxidation in mice liver. Additionally, DLF extracts improved mitochondrial function by preventing the disruption of respiratory chain and suppression of mitochondrial Na+K+-ATPase and Ca2+-ATPase activity. Furthermore, administration with DLF extracts elevated superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and maintained the balance of redox status. This results showed that toxic protection effect of DLF extracts on mice liver is mediated by improving mitochondrial respiratory function and keeping the balance of redox status, which suggesting that DLF extracts could be used as potential toxic protection agent for the liver against hepatotoxic agent.

Antioxidant activity and inhibitory effect of cultivars of Olive (Olea europaea) against lipid peroxidation in mice liver

Objective: The aim of this study is to investigate the in vitro antioxidant activity, the total phenolic and flavonoid contents and the possible protective effects of seven cultivars of olive on lipid peroxidation induced by iron in mice liver.

Influence of cadmium ions on the antioxidant status and lipid peroxidation in mouse liver: protective effects of zinc and selenite ions

Influence of cadmium ions on the antioxidant status and lipid peroxidation in mouse liver: protective effects of zinc and selenite ions

Amelioration of oxidative stress in bio-membranes and macromolecules by non-toxic dye from Morinda tinctoria (Roxb.) roots

Plant dyes have been in use for coloring and varied purposes since prehistoric times. A red dye found in the roots of plants belonging to genus Morinda is a well recognized coloring ingredient. The dye fraction obtained from the methanolic extract of the roots of Morinda tinctoria was explored for its role in attenuating damages caused by H2O2-induced oxidative stress. The antioxidant potential of the dye fraction was assessed through DPPH radical scavenging, deoxyribose degradation and inhibition of lipid peroxidation in mice liver. It was subsequently screened for its efficiency in extenuating damage incurred to biomembrane (using erythrocytes and their ghost membranes) and macromolecules (pBR322 DNA, lipids and proteins) from exposure to hydrogen peroxide. In addition, the non-toxic nature of the dye was supported by the histological evaluation conducted on the tissue sections from the major organs of Swiss Albino mice as well as effect on Hep3B cell line (human hepatic carcinoma). The LC–MS confirms the dye fraction to be morindone. Our study strongly suggests that morindone present in the root extracts of M. tinctoria, in addition to being a colorant, definitely holds promise in the pharmaceutical industry.

Ameliorative effect of emblica officinalis aqueous extract on ochratoxin-induced lipid peroxidation in the kidney and liver of mice

The present study was an attempt at investigating whether the aqueous extract of Emblica officinalis may have an ameliorative effect on ochratoxin-induced lipid peroxidation in the kidney and liver of mice. Adult male albino mice were orally administered 50 microg (LD, low dose) and 100 microg (HD, high dose) of ochratoxin/0.2 ml of olive oil/animal/day for 45 days. The results revealed a significant (p < 0.05), dose-dependent increase in lipid peroxidation as well as a decreased activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase) and non-enzymatic antioxidants (glutathione and total ascorbic acid) in both the organs, as compared to the findings for olive oil-treated control group. Administration of Emblica officinalis aqueous extract (2 mg/animal/day) and ochratoxin for a period of 45 days caused a significant amelioration in the ochratoxin-induced lipid peroxidation in mouse liver and kidney.

Antioxidant Properties of Thymol and Butylated Hydroxytoluene in Carbon Tetrachloride – Induced Mice Liver Injury

Thymol and Butylated hydroxytoluene (BHT) were tested for their ability to inhibit carbon tetrachloride (CCl4)-induced lipid peroxidation in mice liver. To achieve this purpose, four groups of mice were tested, GP I: Animals served as normal control, GP II: Animals injected i.p. with a single dose of CCl4 (0.5 ml/kg B.W), GP III and IV: Animals pretreated by oral administration of thymol or BHT for 6 days, then injected with a single dose of CCl4. After the experimental period, blood was collected, sera separated for ALT assay. The antioxidant activities of the enzymes; superoxide dismutase (SOD), glutathione peroxidase (GS-PX) together with malondialdhyde level were assayed in liver tissues. Results obtained showed that, the antioxidant enzyme activities were significantly decreased while the level of Malondialdhyde (MDA), the indicator of lipid peroxidation, and the activity of alanine aminotransferase (a liver function test) were significantly increased following i.p injection with single sub-lethal hepatotoxic dose of CCl4 as compared to control. Pretreatment of CCl4-intoxicated mice with thymol or BHT for 6 days showed a significant increase in the activities of antioxidant enzymes with simultaneous significant decrease in the level of MDA and ALT as compared to CCI4-treated rats. BHT was a little more potent than thymol in its action. Histopathological examination revealed a necrotic lesion in liver of mice injected with CCl4. Pretreatment with thymol or BHT ameliorates the deleterious effect of CCl4. This is confirmed by the normal appearance of liver tissue. It was speculated that thymol and BHT exert their effects by decreasing lipid peroxidation and enhancing the activities of antioxidant enzymes. For this reason, thymol could be used as hepatoprotective agent with free medication side effects.

Effect of subacute cadmium intoxication on iron and lipid peroxidation in mouse liver

Aloe vera whole leaf extracts are incorporated into a wide variety of topically applied commercial products. Aloe vera whole leaf extracts may contain anthraquinones, which have been shown to generate reactive oxygen species in the presence of ultraviolet A (UVA) light. Exposure to UVA light alone can also generate reactive oxygen species and is associated with photo-damaged and photo-aged skin in humans. This paper examines the photochemical properties of two Aloe vera whole leaf extracts that differed in their anthraquinone content. In the presence of methyl linoleate, the UVA irradiation of Aloe vera leaf extracts induced lipid peroxidation. The amounts of lipid peroxides formed were higher in the Aloe vera leaf extract that contained lower amounts of anthraquinones. Superoxide dismutase and sodium azide inhibited and deuterium oxide enhanced the formation of lipid peroxides, suggesting that singlet oxygen and superoxide were involved in the mechanism. Spin trapping electron spin resonance (ESR) spectroscopy was used to investigate the generation of free radicals by the UVA photo-irradiated Aloe vera plant extracts. ESR measurements indicated that the UVA photo-irradiation of Aloe vera plant extracts produced carbon-centered free radicals. These results suggest that humans exposed to products that contain Aloe vera whole leaf extracts may have enhanced sensitivity to ultraviolet light.

Spinacia oleracea L. protects against gamma radiations: a study on glutathione and lipid peroxidation in mouse liver

The present study deals with the protective effect of Spinacia oleracea L. against radiation-induced oxidative stress, which is evaluated in terms of lipid peroxidation (LPO) product and tissue levels of glutathione. Swiss albino male mice aged 6-8 weeks, weighing 22+/-3 g, each were selected from an inbred colony and divided into four groups. One group served as normal and a second group (extract of S. oleracea L. (SE) treated un-irradiated) were administered methanolic (50%) SE at a dose of 1100mg/kg body wt./day dissolved in distilled water. A third group (untreated-irradiated) was administered distilled water orally, which served as control. A fourth group (SE pre-treated irradiated) was administered methanolic (50%) SE at a dose of 1100 mg/kg body wt./day dissolved in distilled water. Two groups, one untreated-irradiated and another S. oleracea pre-treated irradiated were exposed to 5 Gy of gamma radiation at a rate of 1.07 Gy/min with a source-to-surface distance of 77.5 cm. The animals were autopsied at 1, 3, 7, 15, and 30 days post-exposure. LPO increased after irradiation up to day 15 in the untreated-irradiated group and up to day 7 in SE pre-treated irradiated mice. LPO values were significantly lower in the SE pre-treated irradiated group as compared to their respective untreated-irradiated group at all intervals, which reached normal values from day 7 onward. The percentage of protection observed in the SE pre-treated irradiated group was, 22.22%, 24.8%, 33.25%, 42.84% and 26.36% at 1, 3, 7, 15, 30 days post-exposure, respectively. Radiation-induced glutathione depletion was checked after 7 days' exposure in SE pre-treated irradiated as compared to untreated-irradiated in which recovery started after day 15. Values were significantly higher in the SE pre-treated irradiated group from their respective untreated-irradiated group at all intervals. The percentage of protection observed in the SE pre-treated irradiated group was, 29.41%, 42.68%, 43.55%, 53.81%, 39.28% at 1, 3, 7, 15, 30 days post-exposure, respectively. It is found that radiation-induced augmentation in malondialdehyde contents and depletion in glutathione changes in liver can be altered by S. oleracea L. The protection may be attributed to the combined effects of its constituents rather than to any single factor as the leaves are rich in carotenoid content (beta-carotene, lutein, Zeaxanthine), ascorbic acid, flavonoids and p-coumaric acid. Thus Spinacia, showing protection in liver, may prove promising as a rich source of antioxidants because its use is cost-effective, especially for peoples in adverse and hazardous circumstances who are living in poverty.

Ａｎｔｈｒａｃｙｃｌｉｎｅ新規制癌剤ＭＸ２誘導マウス組織中過酸化脂質上昇に対するリポソーム化の効果

We examined the effect of liposomalization on the changes of lipid peroxide level and glutathione peroxidase (GSHpx) activity in mice tissues after 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) administration. The agreement of the decrease in body weight on the 4th day after double MX2 administration (3.0mg/kg/day×2days, i.p.) was similar to those after adriamycin (ADR) administration (15mg/kg, i.p.). The lipid peroxide level in the heart and liver significantly increased after MX2 double treatment. GSHpx activity in the heart decreased to 80% on the 2nd day after MX2 injection, compared to normal activity. However, these changes are smaller than those after ADR administration (15mg/kg). NADPH-dependent microsomal lipid peroxidation in mouse liver increased, induced more by MX2 than by ADR. The combination of α-tocopherol with MX2 suppressed the increase in the lipid peroxide level by MX2 whereas did not suppress the decrease in GSHpx activity. Thus, it is considered that two mechanisms are involved, i.e., the increase in the lipid peroxide level occurs due to the production of active oxygen from MX2 and due to MX2-induced inhibition of GSHpx. The liposomalization of MX2 suppressed both MX2 induced changes in lipid peroxide level and GSHpx activity. Namely, it is considered that MX2 induced toxicity by these changes were reduced by α-tocopherol combination or liposomalization of MX2.

A subchronic exposure to trichloroethylene causes lipid peroxidation and hepatocellular proliferation in male B6C3F1 mouse liver.

The common groundwater contaminant trichloroethylene (TCE), when given by oral gavage, can produce free radical species during metabolism. Furthermore, TCE end-stage metabolites, trichloroacetic acid and dichloroacetic acid, cause lipid peroxidation in mouse liver. The time courses of lipid peroxidation, free radical generation, and 8-hydroxydeoxyguanosine (8OHdG) formation were used to assess the level of oxidative stress in the liver of B6C3F1 mice dosed orally once daily, 5 days a week for 8 weeks at 0, 400, 800, and 1200 mg/kg TCE in corn oil. Peroxisomal proliferation, cell proliferation, and apoptosis were evaluated at selected times during the study. Lipid peroxidation, as measured by thiobarbituric acid-reactive substances (TBARS), was significantly elevated at the two highest dose levels of TCE on days 6 through 14 of the study. 8OHdG levels were statistically significant in the 1200 mg/kg/day group on days 2, 3, 10, 28, 49, and 56 only. The highest measured free radical load, 307% of oil control, occurred at day 6. A significant increase in cell and peroxisomal proliferation was observed during the same time period in the 1200 mg/kg/day group. Necrosis or an increase in apoptosis was not observed at any dose. The temporal relationship between oxidative stress and cellular response of proliferation, both of which occur and resolve within the same relative time period, suggests that TCE-induced mitogenesis may result from alteration in the liver microenvironment which offers a selective advantage for certain hepatocyte subpopulations.

A Subchronic Exposure to Trichloroethylene Causes Lipid Peroxidation and Hepatocellular Proliferation in Male B6C3F1 Mouse Liver

The common groundwater contaminant trichloroethylene (TCE), when given by oral gavage, can produce free radical species during metabolism. Furthermore, TCE end-stage metabolites, trichloroacetic acid and dichloroacetic acid, cause lipid peroxidation in mouse liver. The time courses of lipid peroxidation, free radical generation, and 8-hydroxydeoxyguanosine (8OHdG) formation were used to assess the level of oxidative stress in the liver of B6C3F1 mice dosed orally once daily, 5 days a week for 8 weeks at 0, 400, 800, and 1200 mg/kg TCE in corn oil. Peroxisomal proliferation, cell proliferation, and apoptosis were evaluated at selected times during the study. Lipid peroxidation, as measured by thiobarbituric acid-reactive substances (TBARS), was significantly elevated at the two highest dose levels of TCE on days 6 through 14 of the study. 8OHdG levels were statistically significant in the 1200 mg/kg/day group on days 2, 3,10, 28, 49, and 56 only. The highest measured free radical load, 307% of oil control, occurred at day 6. A significant increase in cell and peroxisomal proliferation was observed during the same time period in the 1200 mg/kg/day group. Necrosis or an increase in apoptosis was not observed at any dose. The temporal relationship between oxidative stress and cellular response of proliferation, both of which occur and resolve within the same relative time period, suggests that TCE-induced mitogenesis may result from alteration in the liver microenvironment which offers a selective advantage for certain hepatocyte subpopulations.

Effects of perfluoro fatty acids on xenobiotic-metabolizing enzymes, enzymes which detoxify reactive forms of oxygen and lipid peroxidation in mouse liver

Male mice were exposed via their diet to perfluoro fatty acids of various chain-lengths (2–10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2–10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial protein content, microsomal contents of cytochromes P450 and b 5, NADPH-cytochrome P450 reductase activity [measured as NADPH-cytochrome c reductase (EC 1.6.2.3)], microsomal and cytosolic epoxide hydrolase (EC 3.3.2.3) activities, cytosolic DT-diaphorase (EC 1.6.99.2), glutathione transferase (EC 2.5.1.18), glutathione peroxidase (EC 1.11.1.9) and super-oxide dismutase (EC 1.15.1.1) activities, and levels of thiobarbituric acid-reactive material (as an indicator of lipid peroxidation) in the mitochondrial subtraction. The most dramatic changes observed were a 5–9-fold increase in mitochondrial protein, a 3–6-fold increase in the microsomal content of cytochrome P450, a 3–10-fold increase in cytosolic DT-diaphorase activity, an approximately 2-fold increase in cytosolic epoxide hydrolase activity and as much as a 60% decrease in the level of thiobarbituric acid-reactive compounds in the mitochondrial fraction. Smaller increases in microsomal epoxide hydrolase activity and decreases in cytosolic glutathione peroxidase activity were also observed. Of the perfluoro fatty acids tested, perfluorooctanoic acid caused the largest changes in the parameters examined here. Dietary exposure of mice to a 0.02% dose of this substance for 10 days results in a maximal or near-maximal effect in most cases.

Effect of tetrahydropyranyladriamycin (THP-ADR) and 4'-epiadriamycin (4'-epi-ADR) on lipid peroxide levels in mice.

Lipid peroxide levels were measured in mouse tissues to study their relation to the cardiotoxicity of anthracyclines. The effects of tetrahydropyranyladriamycin (THP-ADR) and 4'-epiadriamycin (4'-epi-ADR), which are less cardiotoxic than adriamycin (ADR), were examined. Neither THP-ADR nor 4'-epi-ADR increased the lipid peroxide levels in the heart, however, both increased reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lipid peroxidation in mouse liver and lung microsomes, to the same degree as ADR. Therefore, the results obtained in vitro were not the same as those obtained in vivo. Of all of the anthracyclines tested, only THP-ADR increased the lipid peroxide levels in the lung. Thus, THP-ADR may be pulmotoxic. Differences in the activities of glutathione peroxidase and glutathione S-transferase reflected the differences in lipid peroxide levels.

O-078 - The effect of DMSO treatment on membrane lipid peroxidation in mouse liver after irradiation

O-078 - The effect of DMSO treatment on membrane lipid peroxidation in mouse liver after irradiation

Evidence for carbon tetrachloride-induced lipid peroxidation in mouse liver

The involvement of lipid peroxidation in the mechanism of carbon tetrachloride-induced hepatotoxicity has been a point of controversy. Previous investigators have reported an absence of lipid peroxidative degradation products in mice after exposure to carbon tetrachloride and have used this evidence against the hypothesis that lipid peroxidation is an integral part of the events that cause tissue damage. We have compared the extent of lipid peroxidation caused by carbon tetrachloride between Sprague-Dawley rats and three strains of mice (A/J, BALB/cJ, and C57B1/6J) in in vitro and in vivo systems. Hepatic microsomes isolated from fasted mice of each strain produced more malondialdehyde (a degradation product of lipid peroxidation) per mg microsomal protein than those isolated from fasted rats at all times of incubation with CCl 4. In vivo lipid peroxidation was estimated by the lipid conjugated diene content in hepatic microsomes from the rat and three strains of mice. Increased conjugated diene formation was observed in microsomal lipids of these animals after intraperitoneal injection of CCl 4 (1 ifml/kg as a 20% solution in corn oil) when compared to animals given only corn oil, but no differences were found in the amount of conjugated dienes between mice and rats. Our observations show that the CCl 4-treated mouse undergoes hepatic lipid peroxidation at least as well as the rat, and indicate that lipid peroxidation cannot be excluded as a mechanism of carbon tetrachloride hepatotoxicity as has been claimed on the basis of its ineffectiveness in the mouse.

Effect of Russell's venom on lipid peroxidation in organs of the mouse

The effect of Russell's viper ( Vipera russelli) venom (2.0 mg/kg i.p.) was studied on the rate of lipid peroxidation in mouse liver, heart, lung, kidney and regions of the brain. A significant increase in lipid peroxidation in all organs was observed within 1 hr of venom administration except in liver, where the significant changes were observed after 3 hr. The maximum elevations in liver, heart, lung, kidney, cerebral hemisphere and brain stem were observed after 24 hr, in the cerebellum after 12 hr and in whole brain after 6 hr.