Trans,trans-2,4-decadienal (tt-DDE), a composition of cooking oil fumes,induces oxidative stress and endoplasmic reticulum stress in human corneal epithelial cells

Indoor pollution with cooking oil fumes (COF) as one of the main components is closely related to ocular surface disorders. However, as the most abundant aldehyde in COF, the toxicity of trans, trans-2,4-decadienal (tt-DDE) on human cornea has not been explored before. In the present study, we observed a time- and dose-dependent cytotoxicity induced by tt-DDE in human corneal epithelial (HCE) cells, as evidenced by decreased cell viability, altered cell morphology, and increased proportion of apoptotic cells. Exposure to tt-DDE also led to an increase in reactive oxygen species (ROS) production, MMP loss, and a decrease in intracellular ATP levels. In addition, after exposure to tt-DDE, the expression of endoplasmic reticulum (ER) stress-related proteins (Bip, pIRE1, XBP1, pPERK, peIF2α, ATF4, and CHOP) increased, indicating that ER stress was activated. Moreover, pretreatment of HCE cells with two ER stress inhibitors (200 nM ISRIB or 1 mM 4-PBA) effectively attenuated oxidative stress induced by tt-DDE. These results suggested that tt-DDE could cause damage to HCE cells by triggering oxidative stress and ER stress. Furthermore, regulation of ER stress can be considered as a potential protective method for tt-DDE-induced ocular surface disorders.     

Effects of cooking oil fumes on the genotoxicity and oxidative stress in human lung carcinoma (A-549) cells.

This study investigates the genotoxicity and cytotoxicity of oil fumes, formed when peanut oil is heated, on human lung carcinoma pulmonary type II-like epithelium cells. The major mutagenic compound (trans-trans-2,4-decadienal, t-t-2,4-DDE) contained in oil fumes and its effect on the induction of reactive oxygen species (ROS) is also discussed. The results indicate that the methanolic extract of oil fumes can apparently lead to cytotoxicity and oxidative DNA damage. Glutathione (GSH) content, and the activities of antioxidative enzymes such as GSH reductase, GSH peroxidase and GSH S-transferase were adversely reduced by the methanolic extract of oil fumes. t-t-2,4-DDE could produce superoxide anion, hydrogen peroxide and hydroxyl radicals in a phosphate buffer (pH 7.4), and form intracellular ROS, determined by dichlorofluorescein assay in A-549 cells. Moreover, t-t-2,4-DDE caused significant (P <0.05) oxidative damage of the 8-hydroxy-2'-deoxyguanosine formation in A-549 cells at concentrations from 50 to 200 microM. These results demonstrated that the DNA damage in A-549 cells, induced by t-t-2,4-DDE, was related to the ROS formation. The occurrence of t-t-2,4-DDE, therefore, was of significance in the genotoxicity of oxidized oil and fumes.     

烹调油烟致大鼠体内氧化损伤的研究

通过ＳＤ大鼠连续吸入浓度为３４～５０ｍｇ／ｍ３的烹调油烟染毒,观察不同时相吸入烹调油烟对大鼠体内肺及肝组织Ｓ９组分、血清中ＭＤＡ含量的变化,并观察了血液ＶｉｔＣ含量和血清、肺及肝Ｓ９组分ＳＯＤ酶活性的变化。结果表明：烹调油烟具有产生脂质过氧化的作用,可使肝、肺Ｓ９组分及血清中ＭＤＡ含量增加,使血液中ＶｉｔＣ含量减少,并使血清、肝及肺ＳＯＤ酶活性降低,与阴性对照组比较,差异均有显著性（Ｐ＜０．０５）。烹调油烟组随着染毒时间的延长,其体内ＭＤＡ逐渐增加,而ＳＯＤ逐渐降低     

Inula crithmoides extract protects against ochratoxin A-induced oxidative stress, clastogenic and mutagenic alterations in male rats

Ochratoxin A (OTA) is a mycotoxin often found in cereals and agricultural products. There is unequivocal evidence of renal carcinogenicity of OTA in male rats, although the mechanism of action is unknown. Several reports suggest that exposure to OTA resulted in oxidative stress, genotoxicity and DNA damage. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Inula crithmoides growing in Egypt against OTA-induced mutagenicity and oxidative stress. Forty male Sprague-Dawley rats were divided into four groups and treated for 15 days as follows: control group and the groups treated with OTA (3mg/kg b.w), I. crithmoides extract alone (370mg/kg b.w) and OTA+I. crithmoides extract. Blood and tissue samples were collected for different biochemical analyses. Bone marrow micronucleus test and blood for random amplified polymorphism DNA-PCR (RAPD-PCR) method were performed to assess the antigenotoxic effect of the extract. The results indicated that OTA induced toxicological effects typical to those reported in the literature and increased the frequencies of MnPCEs in bone marrow. The RAPD-PCR analysis revealed the appearance of new bands in DNA resulting from genetic alteration. The extract alone was safe and succeeded in counteracting the oxidative stress and protect against the cytotoxicity resulting from OTA.     

Genotoxicity,oxidative stress and lysozyme induction in Clarias gariepinus chronically exposed to water-soluble fraction of burnt tire ash

Ecotoxicology - The safety of aquatic ecosystems has been compromised by numerous anthropogenic activities, especially leachates from non-point source toxicants, leaching into aquatic systems. This...     

Genotoxicity studies in the ST cross of the Drosophila wing spot test of sunflower and soybean oils before and after frying and boiling procedures

Sunflower and soybean oils were tested for genotoxicity in the Drosophila wing somatic mutation and recombination assay. Results indicate that both oils produce genotoxic effects when tested without any previous frying or boiling processes. Boiling sunflower oil during fifteen, thirty and sixty minutes significantly increased its genotoxic response; nevertheless, after frying potatoes this oil showed a significant decrease in the genotoxic activity. On the other hand, boiling and frying soybean oil in the same conditions results in a decrease of its genotoxic potential. We have also detected that the amount of total polar materials increases significantly in oils submitted to frying or boiling process. Nevertheless, in oils obtained after frying potatoes, the amount of TPM was higher than after boiling. It is suggested that this effect is probably due to the amount of non-volatile TPM, the fatty acid composition of the oils, the types of frying oil, the high frying temperature and time, and the number of boiling and frying. This is the first study reporting genotoxicity data in Drosophila for the boiling and frying of both sunflower and soybean oils.     

Genotoxicity assessment and oxidative stress responses in freshwater African catfish Clarias gariepinus exposed to fenthion formulations

Fenthion is one of the most widely used organophosphate insecticides for the control of many varieties of pests in Nigeria. The genotoxic effect of the pesticide was evaluated in the blood erythrocytes of Clarias gariepinus using the micronucleus (MN) test. The oxidative stress parameters were also studied in the liver and gill tissues. Fish were exposed to 2.0, 4.0, and 8.0?mgL^?1 of fenthion and sampling was done on days 1, 7, 14, 21 and after 7-day recovery. Micronuclei induction was highest (7.55) on day 14 at all concentrations in the peripheral blood cells. Oxidative stress was evidenced by increased lipid peroxidation (LPO). Maximum LPO values of 62.47% and 71.17% were observed in the gill and liver tissues respectively in C. gariepinus exposed to 8.0?mgL^?1 concentration of fenthion. There were alterations in the values of reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) during the exposure and recovery periods. The 7-day recovery period was not adequate to eliminate fenthion-induced changes as LPO, CAT, and GR activity remain elevated. However, MN frequency and activity of SOD, GSH, and GPx (except at 8.0?mgL^?1) recovered. The present findings give further credence on the integrated use of MN test and oxidative stress parameters in risk assessment of pollutants in aquatic ecosystem.     

Protective effect of olive oil and colocynth oil against cadmium-induced oxidative stress in the liver of Wistar rats

Cadmium (Cd) is one of the most common heavy metal pollutants. It is accumulated particularly in liver and kidney. The present study examined the possible protective effect of olive oil and colocynth oil consumption against Cd-induced damage on plasma lipids and stress biochemical parameters of rats. Male albino Wistar rats were randomly divided into 6 groups of 5 animals each and treated orally with Cd (50 mg/l), olive oil and colocynth oil (4%) alone or in combination with cadmium for 8 weeks. It was shown that Cd exposure induced significant increases in the activities of serum alanine aminotransferase, aspartate aminotransferase, lipid peroxidation levels (MDA) and protein carbonyl contents in exposed groups of rats compared to control group while the antioxidant enzymes, reduced glutathione and vitamins (C, A and E) were significantly decreased. Co-treatment with olive oil or colocynth oil significantly improved the oxidative damage induced by Cd. The antioxidant potential in plasma and liver were markedly restored with a significant decline in MDA levels and activity of transaminases.In conclusion, these results suggest that olive oil or colocynth oil consumption could protect the rat liver against Cd-induced injury by increasing the activities of antioxidant enzymes and reducing oxidative stress.     

Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices: Involvement of oxidative stress and glutamatergic system

Excessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been pointed as two key mechanisms in methylmercury-toxicity. Thus, here we investigate the involvement of glutamatergic system in methylmercury (MeHg) neurotoxicity and whether diphenyl diselenide, ebselen and guanosine could protect cortical rat brain slices from MeHg-induced ROS generation. MeHg (100 and 200 μM) increased 2′,7′-dichlorodihydrofluorescin (DCFH) oxidation after 2 h of exposure. At 50 μM, MeHg increased DCFH oxidation only after 5 h of exposure. Guanosine (1 and 5 μM) did not caused any effect per se; however, it blocked the increase in DCFH caused by 200 or 50 μM MeHg. Ebselen (5 and 10 μM) decreased significantly the DCFH oxidation after 2 and 5 h of exposure to MeHg. Diphenyl diselenide (5 μM) did not change the basal DCFH oxidation, but abolished the pro-oxidant effect of MeHg. MK-801 also abolished the pro-oxidant effect of MeHg. These results demonstrate for the first time the potential antioxidant properties of organoseleniun compounds and guanosine against MeHg-induced ROS generation after short-term exposure in a simple in vitro model. In conclusion, endogenous purine (guanosine) and two synthetic organoselenium compounds can modulate the pro-oxidant effect of MeHg in cortical brain slices.     

Mutagenicity and aromatic amine content of fumes from heated cooking oils produced in Taiwan.

According to toxicological studies, there are several unidentified mutagens derived from cooking oil fumes appearing in kitchens of Chinese homes where women daily prepare food. Data are limited to an analysis of aromatic amines from cooking oil fumes, which are known to be carcinogenic for bladder cancer. Fume samples from three different commercial cooking oils frequently used in Taiwan were collected and analysed for mutagenicity in the Salmonella/microsome assay. Aromatic amines were extracted from the samples and identified by HPLC and confirmed by gas chromatography/mass spectrometry (GC/MS). Extracts from three cooking oil fumes were found to be mutagenic in the presence of S-9 mix. All samples contained 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP). Concentrations of 2-NA and 4-ABP were 31.5 and 35.7 microg/m3 in fumes from sunflower oil, 31.9 and 26.4 mg/m3 in vegetable oil, and 48.3 and 23.3 microg/m3 in refined-lard oil, respectively. Mutagenicities of the three cooking oil condensates were significantly reduced (P<0.05) by adding the antioxidant catechin (CAT) into the oils before heating. Significant difference existed between the amounts of aromatic amines with and without adding CAT (P<0.05). These results indicate that exposure to cooking oil fumes in Taiwan might be an important but controllable risk factor in the aetiology of bladder cancer.     

Olive oil and its phenolic compounds (hydroxytyrosol and tyrosol) ameliorated TCDD-induced heptotoxicity in rats via inhibition of oxidative stress and apoptosis

Context: Naturally occurring polyphenols including olive oil (OO) and its constituents hydroxytyrosol (HT) and tyrosol (TY), consumed in the Mediterranean diet, have shown to treat various ailments due to their remarkable antioxidant properties.

Objective: The present study investigates the hepatoprotective effects of OO and its phenolic compounds HT and TY against TCDD-induced hepatotoxicity in male Wistar rats.

Materials and methods: TCDD was administered at a dose of 100?ng/kg p.o. for 20?d. Administration of OO (10?ml/kg; oral), HT (0.5?mg/kg; oral), and TY (30?mg/kg; i.p) was started 5?d prior to TCDD administration, and continued for 25?d with or without TCDD administration. At the end of the experiment (25?d), blood was taken for biochemical analyses and liver for the measurement of macromolecular damages, antioxidant status, expressions of CYP1A1, and apoptotic factors.

Results: TCDD administration resulted in significant (p?<?0.05) increase in the level of hepatic stress markers ALT (101.6?±?3.07?IU/l), AST (295.0?±?3.0?IU/l), and ALP (266.66?±?3.7?IU/l). Also, biochemical analyses of liver reported elevation in nitrite and protein carbonyl content and depletion of NQO1 and HO. However, OO, HT, and TY restored the antioxidant status. Protein expressions by Western Blot technique showed an increase in the level of CYP1A1 and Bax and a decreased level of Bcl-2 on TCDD treatment, and vice versa on OO, HT, and TY treatment.

Discussion and conclusion: Our work concludes that dietary supplementation of OO, HT, and TY could serve as a potential preventive drug for TCDD-induced hepatotoxicity.     

Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes,oxidative stress,and acetaminophen toxicity in rats

The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO)] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg) and 400 LO (400 mg/kg) and its major component, citral (240 mg/kg), on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(P)H:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5′-diphospho (UDP) glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen.     

Paracetamol: overdose-induced oxidative stress toxicity,metabolism, and protective effects of various compounds in vivo and in vitro

Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.     

Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats

Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the non-toxigenic and non-pathogenic marine protist, Ulkenia sp. The safety of DHA-algal oil was assessed in a subchronic toxicity study and in genotoxicity studies. In a 90-day study, rats were orally administered water or DHA-algal oil at concentrations of 0, 500, 1000, and 2000 mg/kg in combination with 2000, 1500, 1000 or 0 mg/kg DHA-containing fish oil, respectively. Additional animals were administered water, 2000 mg/kg DHA-algal oil, or 2000 mg/kg fish oil for 90 days, followed by a 4-week recovery phase. No treatment-related effects were observed in clinical observations, food and water consumption, mortality, gross pathology, and histopathology. Increased body weights and liver weights in oil-treated groups were attributed to the large lipid load and were not regarded as toxicologically significant. Furthermore, no treatment-related differences in the measured parameters between the DHA-algal oil and fish oil groups were detected. In genotoxicity experiments, DHA-algal oil exerted no mutagenic activity in various bacterial strains, nor did it induce chromosomal aberrations in Chinese hamster fibroblast cells. These results support the safety of DHA-algal oil as a dietary source of DHA.     

Resveratrol may reduce oxidative stress induced by platinum compounds in human plasma, blood platelets and lymphocytes

Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic compound found in grapes and wine, has been shown to have anti-inflammatory, anti-oxidant, anti-tumor and anti-platelet activities. Using different methods, we show that resveratrol reduces oxidative stress induced by cisplatin (cis-diamminedichloroplatinum II) and selenium-cisplatin conjugate ([NH(3)](2)Pt(SeO(3)), Se-Pt) in human blood platelets, lymphocytes and plasma. Resveratrol decreased the production of 8-epi-prostaglandin F(2) (a biomarker of lipid peroxidation) in control blood platelets and platelets treated with platinum compounds (10 microg/ml), and markedly reduced activities of different anti-oxidative enzymes (glutathione peroxidase, superoxide dismutase and catalase) in these cells. A combined action of resveratrol and Se-Pt evoked a significant decrease of DNA damage (measured by comet assay) in lymphocytes compared with cells treated with Se-Pt only. Resveratrol also caused a distinct reduction of total anti-oxidant level in plasma after incubation with platinum compounds. Therefore, anti-oxidative activity of resveratrol may diminish oxidative stress and damage to cellular biomolecules (lipids, proteins and DNA) induced by platinum compounds.     

Cyclic fatty acid monomer formation in domestic frying of frozen foods in sunflower oil and high oleic acid sunflower oil without oil replenishment.

During the frying process, oxidation, hydrolysis, polymerization, isomerization, and cyclization occur. Polymers and Cyclic fatty acid monomers (CFAM) are potentially toxic, and the latter are detected at relatively low levels (0.01-0.7%) in used frying oils. Twenty fryings of different frozen foods were carried out over 10 consecutive days in sunflower oil (SO) and in high oleic acid sunflower oil (HOSO). Fatty acid methyl ester derivates were hydrogenated with platinum oxide catalyst under hydrogen. Ethyl palmitate was added as an internal standard before hydrogenation. The CFAM obtained were isolated, concentrated and quantified by HPLC using a reverse-phase column followed by gas chromatography. Linear adjustments between total and individual CFAM content and the number of frying operations performed with both oils were established by analysis of variance. The comparison between linear equation adjustments of both oils was performed by a two-way analysis of covariance. After 20 fryings 15.4 +/- 0.06 g polar content/100 g oil, 7.15 +/- 0.08 g polymers/ oil, 11.52 +/- 0.08 g polymers/100g oil and 855 +/- 8.9 mg CFAM/kg oil were detected in SO. A 10 mg/100 mg oil of altered fatty acid content correspond to 700 mg/kg CFAM, while 25% polar material and 10% polymer content would correspond to about 850-1,000 mg CFAM/kg oil. Data suggest that frying with SO produces in each new frying 9 mg CFAM/kg more than frying with HOSO (p < 0.001). After frying cyclopentyl structures were more than twice as abundant as cyclohexyl fatty acids in both oils. Bicyclic compound formation was significantly higher in SO (p < 0.001). Because digestion and absorption of polar material, polymers and CFAM occur, data clearly show the advantageousness and advisability of frying with HOSO rather than SO.     

Metallothioneins, oxidative stress and the cardiovascular system

Metallothioneins (MTs) discovered four decades ago as metal binding low molecular weight thiol proteins, in recent years, have generated immense interest due to their involvement in various physiological and pathophysiological events. In spite of the recent advances in the knowledge base in MTs, no specific study on the isolation or characterization of MTs isoforms and their precise function in the heart has been conducted. Although most stress conditions in the heart do not produce much change in myocardial MTs, TNF-alpha and IL-6 do induce MT in the heart to the extent comparable with the liver. Cardiotoxicity of anticancer drugs and vulnerability of the heart to other oxidative stress conditions may partially be due to lack of inducibility of MT in the heart by these interventions. A clear understanding of induction of MTs in the heart may help in the development of better approaches to modulate the pathogenesis of cardiomyopathies and heart failure.     

Vetiver oil (Java) attenuates cisplatin-induced oxidative stress,nephrotoxicity and myelosuppression in Swiss albino mice

Clinical efficacy of the widely used anticancer drug cisplatin is limited due to its adverse side effects in normal tissues mediated by oxidative stress. This study was aimed to investigate the protective effects of vetiver acetate oil, Java (VO) against cisplatin-induced toxicity in Swiss albino mice. The ameliorating potential was evaluated by orally priming the animals with VO at doses 5, 10 or 20 mg/kg bw for 7 days prior to cisplatin treatment. Acute toxicity in mice was induced by injecting cisplatin (3 mg/kg bw) intraperitoneally for 5 consecutive days. Significant attenuation of renal toxicity was confirmed by histopathological examination, lowered levels of serum blood urea nitrogen, creatinine and reduced DNA damage. VO also compensated deficits in the renal antioxidant system. VO intervention significantly inhibited DNA damage, clastogenic effects, and cell cycle arrest in the bone marrow cells of mice. Hematological parameters indicated attenuation of cisplatin-induced myelosuppression. Overall, this study provides for the first time that VO has a protective role in the abatement of cisplatin-induced toxicity in mice which may be attributed to its antioxidant activity.