γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes

Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5 mg/kg of CdCl₂, and then treated with ORY (50 mM in canola oil, 5 mL/kg). Testes were removed after 24 h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity.     

Taxifolin mitigates oxidative DNA damage in vitro and protects zebrafish (Danio rerio) embryos against cadmium toxicity

Taxifolin (TAX) is a natural source of bioflavonoid found in various conifers. In this study, initially we investigated the antioxidant potential of TAX under in vitro assays such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric-ion reducing power (FRAP) and hydroxyl radical (OH). The activities of DPPH, ABTS, FRAP and OH radical levels were significantly inhibited by TAX with an IC₅₀ values of 16.48, 66.34, 18.17 and 11.42 μg/ml, respectively. Secondly, TAX exhibited a strong protection against OH mediated DNA damage on pUC19 plasmid DNA at 1.0 μg/ml. Finally, we evaluated the protective mechanism of TAX against cadmium intoxicated zebrafish embryos (Danio rerio). We found that embryos exposed to 100 μM Cd exhibited significantly reduced survival, delayed hatching and phenotypic abnormalities at 24, 48, 72 and 96 hours post fertilization (hpf). Similarly, Cd intoxicated embryos showed significantly increased cardiac function (131 beats/min) at 60 hpf. Conversely, treatment with TAX (0.1, 1.0 and 10 μM) significantly enhanced the antioxidant enzyme levels (SOD, CAT, GPx and GR) by reducing the lipid peroxidation (MDA) in zebrafish embryos. Collectively, our results concluded that TAX could act as a potent redox scavenger against oxidative DNA damage and also functions as a crucial suppressor of Cd toxicity in zebrafish embryos.     

Evaluation of 8-hydroxy-2-deoxyguanosine and NFkB activation,oxidative stress response,acetylcholinesterase activity,and histopathological changes in rainbow trout brain exposed to linuron

Linuron is a widely used herbicide to control grasses and annual broad leaf weeds. It is known that linuron has toxic effects on different organisms. However, the toxic effects of linuron on aquatic organisms, especially fish, is completely unknown. Thus, we aimed to investigate changes in 8-hydroxy-2-deoxyguanosine (8-OHdG) and nuclear factor kappa B (NFkB) activity, histopathological changes, antioxidant responses and acetylcholinesterase (AChE) activity in rainbow trout brain after exposure to linuron. Fish were exposed to 30 μg/L, 120 μg/L and 240 μg/L concentrations of linuron for twenty-one days. Brain tissues were taken from fish for 8-OHdG and NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity, lipid peroxidation (LPO), and reduced glutathione (GSH) levels. Our data indicated that high linuron concentrations caused a decrease in GSH levels, SOD and CAT activities in brain tissues (p < 0.05). LPO levels were significantly increased by 240 μg/L linuron. All concentrations caused a significant inhibition in brain AChE enzyme activity (p < 0.05). Immunopositivity was detected for 8-OHdG and NFkB, and linuron exposure caused histopathological damage to the brain tissues. The results of this study can provide useful information for understanding of linuron-induced toxicity.     

Benchmark dose for estimation of cadmium reference level for osteoporosis in a Chinese female population

In this study, the reference level of cadmium in urine and blood related with bone damage was assessed using benchmark dose in a Chinese female population. Total of 338 women was recruited, and urine and blood samples were collected from each individual for determination of cadmium in urine (UCd) and blood (BCd). Bone mineral density was measured by dual energy X-ray absorptiometry. BMD and BMDL were calculated corresponding to additional risk of 5% and 10%. With benchmark response (BMR) of 5%/10%, the BMD of BCd, UCd related with osteoporosis was 1.88 μg/L/3.23 μg/L and 5.30 μg/g crea/9.06 μg/g crea, and the BMDL-05 was 1.39 μg/L/2.38 μg/L and 3.78 μg/g crea/6.36 μg/g crea; the BMD of BCd, UCd related with low bone mass was 0.95 μg/L/3.12 μg/L and 3.12 μg/g crea/5.87 μg/g crea, and the BMDL-05 was 0.72 μg/L/1.35 μg/L and 2.14 μg/g crea/3.99 μg/g crea. The BMD of UCd in people over 60 years old was much lower than that of people less than 60 years old. BMD value was related with ages and effects biomarkers. Our data showed that BMD of UCd associated with osteoporosis was lower than that previously estimated.     

Safety evaluation of metal exposure from commonly used moisturizing and skin-lightening creams in Nigeria

The concentrations of ten metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn and Al) were measured in some commonly used moisturizing and skin-lightening creams in Nigeria with a view to providing information on the risk of exposure to metals from the use of these products. The metal concentrations in these products were measured by atomic absorption spectrometry after acid digestion of the samples. The measured concentrations of metals in the skin moisturizing creams ranged from <0.15 to 6.3 μg/g Cd, <0.02 to 17.5 μg/g Cu, 2.25 to 6.25 μg/g Cr, <0.25 to 124.3 μg/g Al, 0.2 to 7.3 μg/g Pb, <0.03 to 10.7 μg/g Ni, 17.3 to 372.0 μg/g Zn, <0.02 to 1.0 μg/g Co, 17.75 to 28.8 μg/g Mn, <0.1 to 89.8 μg/g Fe while the concentrations of metals in the skin-lightening products ranged from <0.15 to 16.5 μg/g Cd, <0.02 to 10.0 μg/g Cu, 4.25 to 8.0 μg/g Cr, <0.25 to 128.0 μg/g Al, 0.5 to 4.5 μg/g Pb, <0.03 to 1.65 μg/g Ni, 24.7 to 267.5 μg/g Zn, <0.02 to 2.5 μg/g for Co, 19.3 to 31.8 μg/g Mn, 9.5 to 211.63 μg/g Fe. In a significant number (>93%) of the samples investigated the concentrations of Pb, Cd, Ni and Co were below the specified limit, or the maximal limit for impurities in colour additives in cosmetics for external use. However, Cr was found at concentrations above the allergenic limit of 1 μg/g. The results also showed that skin-lightening creams contained higher concentrations of the studied metals than the moisturizing creams, except for Ni, which indicates that persons who uses skin-lightening creams in preference to moisturizing ones, are exposed to higher concentrations of metals.     

Trophic transfer of Cd from larval chironomids (Chironomus riparius) exposed via sediment or waterborne routes,to zebrafish (Danio rerio): Tissue-specific and subcellular comparisons

Zebrafish were fed chironomid larvae (8% wet weight daily ration) for 7 days, followed by 3 days of gut clearance in a static-renewal system. Regardless of whether the chironomids had been loaded with Cd via a waterborne exposure or sediment exposure, they had similar subcellular distributions of Cd, with the largest areas of storage being metal rich granules (MRG) > organelles (ORG) > enzymes (ENZ) except that sediment-exposed chironomids had significantly more Cd in the metallothionein-like protein (MTLP) fraction, and significantly less Cd in the cellular debris (CD) fraction. When zebrafish fed sediment-exposed chironomids (153 ± 11 μg Cd/g dry weight) were compared directly to zebrafish fed waterborne exposed chironomids (288 ± 12 μg Cd/g dry weight), identical whole-body Cd levels were observed, despite the difference in the concentration in the food source. Thus trophic transfer efficiency (TTE) of Cd was significantly greater from sediment-exposed chironomids (2.0 ± 0.5%) than from waterborne-exposed chironomids (0.7 ± 0.2%). Subsequent tests with waterborne exposed chironomids loaded to comparable Cd concentrations, as well as with Cd-spiked manufactured pellets, demonstrated that TTEs were concentration-independent. In all treatments, zebrafish exhibited similar subcellular storage of Cd, with the greatest uptake occurring in the ORG fraction followed by the ENZ fraction. However, neither trophically available metal (TAM) nor metabolically available fractions (MAF) were good predictors for the TTEs found in this study. Tissue Cd concentrations were highest in the kidney and gut tissue, then liver, but lower in the gill, and carcass. Overall, the gut and carcass contributed ≥71% to total body burdens on a mass-weighted basis. This study presents evidence that Cd may be acquired by fish from natural diets at levels of environmental relevance for contaminated sites, and that the exposure route of the prey influences the TTE.     

Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: Role of oxidative stress and caspase-3

Cadmium (Cd) is an environmental and industrial pollutant that can induce a broad spectrum of toxicological effects that affect various organs in humans and experimental animals. This study aims to investigate the effect of betaine supplementation on cadmium-induced oxidative impairment in rat kidney. The animals were divided into four groups (n = 10 per group): control, cadmium, betaine and betaine + cadmium (1) saline control group; (2) cadmium group in which cadmium chloride (CdCl₂) was given orally at a daily dose of 5 mg/kg body weight for four weeks; (3) betaine group, in which betaine was given to rats at a dose of 250 mg/kg/day, orally via gavage for six weeks; (4) cadmium + betaine group in which betaine was given at a dose of 250 mg/kg/day, orally via gavage for two weeks prior to cadmium administration and concurrently during cadmium administration for four weeks. Cadmium nephrotoxicity was indicated by elevated blood urea nitrogen (BUN) and serum creatinine levels. Kidneys from cadmium-treated rats showed an increase in lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) concentration and reductions in total antioxidant status (TAS), reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase concentration (SOD) and catalase activity. Caspase-3 activity, a marker of DNA damage was also elevated in renal tissues of cadmium-treated rats. Pre-treatment of rats with betaine substantially attenuated the increase in BUN and serum creatinine levels. Betaine also inhibited the increase in TBARS concentration and reversed the cadmium-induced depletion in total antioxidant status, GSH, GSH-Px, SOD and catalase concentrations in renal tissues. Renal caspase-3 activity was also reduced with betaine supplementation. These data emphasize the importance of oxidative stress and caspase signaling cascade in cadmium nephrotoxicity and suggest that betaine pretreatment reduces severity of cadmium nephrotoxicity probably via antioxidant action and suppression of apoptosis.     

Capsaicin prevents ethanol-induced teratogenicity in cultured mouse whole embryos

Prenatal exposure to alcohol promotes the level of reactive oxygen species within embryos and results in developmental disorders. In this study, we investigated the effect of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the major pungent ingredient in red peppers, on ethanol-induced teratogenicity in mouse embryos (embryonic days 8.5–10.5). In response to ethanol administration (1.0 μl/ml), developmental parameters such as yolk sac circulation, allantois, heart, hindbrain, midbrain, forebrain, otic and optic systems, branchial bar, olfactory system, forelimb, hindlimb, and somites decreased significantly in comparison with those of control group (p < 0.05). However, the concurrent administration of capsaicin (1 × 10⁻⁸ μg/ml or 1 × 10⁻⁷ μg/ml) and ethanol significantly ameliorated most of the morphological scores excepting yolk sac circulation and hindlimb scores (p < 0.05). Furthermore, the levels of superoxide dismutase activity and cytoplasmic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase mRNAs in the ethanol-treated embryos recovered to the levels observed in control embryos by capsaicin co-administration. These results indicate that capsaicin has a protective effect against ethanol-induced teratogenicity via an antioxidative activity.     

Cassiae semen,a seed of Cassia obtusifolia,has neuroprotective effects in Parkinson’s disease models

Cassiae semen, a commonly consumed tea and medicinal food, has been shown to have multiple therapeutic actions related to the prevention of dementia and ischemia. In this study, we investigated the effects of extract of Cassiae semen (COE) against neurotoxicities in in vitro and in vivo Parkinson’s disease (PD) models. In PC12 cells, COE attenuated the cell damage induced by 100 μM 6-hydroxydopamine (6-OHDA) stress in MTT assay, and it inhibited the overproduction of reactive oxygen species, glutathione depletion, mitochondrial membrane depolarization and caspase-3 activation at 0.1–10 μg/ml. In addition, COE showed radical scavenging activity in the DPPH and ABTS assays. In mesencephalic dopaminergic (DA) culture, COE protected DA cells against 10 μM 6-OHDA- and 10 μM 1-methyl-4-phenylpyridine-induced toxicities at 0.1–1 μg/ml. We also evaluated the effect of COE in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, COE (50 mg/kg, 15 days) + MPTP (30 mg/kg, 5 days)-treated group had decreased T-turn and T-LA which were longer in MPTP group. Moreover, COE significantly protected DA neuronal degeneration induced by MPTP in the substantia nigra and striatum of these mice. These results demonstrate that COE can prevent DA neurons against the toxicities involved in PD.     

Oxidative stress,endocrine disruption,and malformation of Bufo gargarizans embryo exposed to sub-lethal cadmium concentrations

Thyroid hormone (TH) is critical for vertebrate postembryonic development as well as embryonic development. Chinese toad (Bufo gargarizans) embryos were exposed to different concentrations of cadmium (5, 50, 100, 200 and 500 μg Cd L⁻¹) for 7 days. Malformations were monitored daily, and growth and development of embryos were measured at day 4 and 7, and type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. In addition, superoxide dismutase (SOD), glutathione peroxidase (GPx) and heat shock proteins (HSPs) mRNA expression were examined to evaluate the ability of scavenging ROS. Our results demonstrated a bimodal inhibitory effect of Cd on the embryo growth and development of Bufo gargarizans. Reduced mean stage, total length and weight were observed at 5, 50, 200 and 500, but not at 100 μg Cd L⁻¹. Embryos malformation occurred in all cadmium treatments. Morphological abnormalities of embryos are characterized by axial flexures, abdominal edema, stunted growth and fin flexure. Real-time PCR results show that exposure to cadmium down-regulated TRα and Dio3 mRNA expression and up-regulated Dio2 mRNA level. SOD and GPx mRNA expression was significantly up-regulated after cadmium exposure. We concluded that cadmium could change mRNA expression of TRα, Dio2 and Dio3 leading the inhibition of growth and development of B. gargarizans embryo, which suggests that cadmium might have the endocrine-disrupting effect in embryos. Moreover, the reduced ability of scavenging ROS induced by cadmium might be responsible for the teratogenic effects of cadmium.     

In vitro study of the effect of metabolism enzymes on benzo(a)pyrene-induced DNA damage in the scallop Chlamys farreri

Acute toxicity effect of benzo(a)pyrene (BaP) on isolated scallop (Chlamys farreri) digestive gland cells was studied and a dose-dependent increase in toxicity was observed. The 8 μg/L of BaP had a significant toxic effect on isolated cells (p < 0.05). In order to study the mechanism of CYP450, GST, SOD and MXR transporters involved in the production of DNA strand breakage such as DNA adduct formation and oxidative DNA damage by BaP were investigated in isolated digestive gland cells. Isolated cells were exposed in vitro to 0.8 μg/L of BaP for 24 h in the dark at 25 °C in the absence or presence of cytochrome P450 inhibitor, GST inhibitor, Pgp inhibitor and antioxidant enzyme inhibitor. DNA adduct and 8-OHdG content were measured using the Enzyme-linked Immunosorbent Assay. The result indicated that DNA strand breakage was increased to 2 times compared with the control in the 0.8 μg/L of BaP treatment groups. The BaP-induced DNA adduct and 8-OHdG content increased significantly by inhibiting GST, while only 8-OHdG increased significantly when SOD was inhibited. The content of DNA adduct and 8-OHdG had no significant change when CYP450 was inhibited, while it decreased significantly when MXR transporters were inhibited. The result proved that GST play a key role in eliminating the BaP-induced DNA adduct and 8-OHdG, and SOD also had an important function in reducing the production of BaP-induced 8-OHdG.     

Effect of 4-methylpyrazole on antioxidant enzyme status and lipid peroxidation in the liver of rats after exposure to ethylene glycol and ethyl alcohol

BackgroundThe aim of the conducted studies was to evaluate the effect of 4-methylpyrazole, increasingly used in detoxifying treatments after ethylene glycol poisoning, on the activity of some antioxidant enzymes and lipid peroxidation formation in the liver of rats after experimental co-exposure to ethylene glycol and ethyl alcohol.MethodsThe trials were conducted on adult male Wistar rats. Ethylene glycol (EG) at the dose of 3.83 g/kg bw and ethyl alcohol (EA) at the dose of 1 g/kg bw were administered po, and 4-methylpyrazole (4-MP) at the dose of 0.01 g/kg bw was administered ip. Parameters of antioxidant balance were evaluated in hepatic cytosol, including the activity of the following enzymes: glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation level (TBARS).ResultsThe results suggest that evaluation of the effects of administrated 4-MP after co-exposure to EG and EA in the liver revealed statistically significant changes on antioxidant enzyme system and malondialdehyde formation.ConclusionThe changes in biomarkers activity indicate a greater production of free radicals which exceeds the capability of antioxidant system, appearing with oxidative stress in the group of animals treated by 4-MP combined with EG and EA.     

Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: Protective role of coenzyme Q10 and Vitamin E

The aim of this study was to investigate the protective role of coenzyme Q₁₀ (CoQ₁₀, 20 mg/kg) and Vitamin E (Vit E, 20 IU/kg) alone or in combination against cadmium (Cd, 0.4 mg/kg) induced lipid peroxidation and changes in antioxidant defense system in the rat testes. The obtained results showed that Cd increased lipid peroxidation in the testes, suggesting that Cd-induced oxidative stress, while CoQ₁₀ and Vit E treatment reversed this change to control values. Acute intoxication with Cd was followed by significantly decreased activity of antioxidant enzymes (SOD, CAT, GSH-Px, GR and GST). Vitamins C and E concentrations also significantly declined in Cd-exposed rat testes. Treatment with CoQ₁₀ and Vit E reversed Cd-induced alterations of antioxidant defense system and significantly prevented Cd-induced testes damage. These results suggest that both CoQ₁₀ and Vit E function as a potent antioxidant in protection of rats testes against the oxidative stress induced by Cd.     

Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals

Nonsynonymous single nucleotide polymorphisms in glutathione s-transferase pi 1 (GSTP1; Ile/Val 105, Ala/Val 114) have been associated with altered toxicant metabolism in epidemiological cohorts. We explored the impact of GSTP1 genotype on enzyme kinetics and heavy metal inhibition in vitro. Four GSTP1 allozymes (105/114: Ile/Ala, Val/Ala, Ile/Val, Val/Val) were expressed in and purified from Escherichia coli. Enzyme activity assays quantifying the rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) revealed significant differences in kinetic parameters depending on genotype (p < 0.01). Allozymes with Ile105 had better catalytic efficiency and greater affinity for CDNB (mean ± SEM: Ile105 Ala114 K_m = 0.33 ± 0.07 mM vs. Val105 Ala114 K_m = 1.15 ± 0.07 mM). Inhibition of GSTP1 activity by heavy metals was assessed following treatment with mercury (inorganic-HgCl₂, methylmercury-MeHg), selenium, cadmium, lead, arsenic, and manganese. All allozymes were inhibited by HgCl₂ (IC₅₀ range: 24.1–172 μM), MeHg (93.9–480 μM), and selenium (43.7–62.8 μM). Genotype significantly influenced the potency of mercury with GSTP1 Ile105 Val114 the least sensitive and Val105 Ala114 the most sensitive to inhibition by HgCl₂ and MeHg. Overall, genotype of two nonsynonymous polymorphisms in GSTP1 influenced enzyme kinetics pertaining to an electrophilic substrate and inhibition by two mercury species.     

Comparative study of the quercetin,ascorbic acid,glutathione and superoxide dismutase for nitric oxide protecting effects in mouse gastric fundus

The aim of this work was to compare the preventing capacity of quercetin with Cu/Zn superoxide dismutase (Cu/Zn SOD), ascorbic acid and glutathione on nitric oxide (NO)-induced relaxation in mouse gastric fundus. Furthermore, the effects of the quercetin on the tissue level of total oxidant and antioxidant was investigated. Nitrergic stimulation (4 Hz, 25 V, 0.1 ms, 10 s-train) and exogenous NO (10 μM) induced relaxation. Pyrogallol (10 μM), hydroquinone (100 μM) and LY83583 (6-Anilino-quinolin-5,8-quinone, 5 μM) inhibited nitrergic relaxations. The inhibition observed with pyrogallol, hydroquinone and LY83583 was prevented by quercetin (0.1 μM). Also, ascorbic acid (500 μM), glutathione (100 μM) and Cu/Zn SOD (100 U/ml) prevented the inhibitory effect of superoxide anion generators on the relaxation to nitrergic stimulation and NO. Diethyldithiocarbamic acid (DETCA; 8 mM) inhibited nitrergic relaxations. DETCA-induced inhibition on nitrergic stimulation and NO-induced relaxation was prevented by quercetin, ascorbic acid, glutathione or Cu/Zn SOD. DETCA plus pyrogallol, hydroquinone or LY83583 strengthened the inhibition on the relaxations. Also, pre-treatment with quercetin, ascorbic acid and glutathione prevented the inhibitory effect of DETCA plus LY-83583 on the relaxation to nitrergic stimulation and NO but Cu/Zn SOD did not prevent this inhibition. Also, quercetin increased tissue total antioxidant capacity and decreased tissue oxidant level and oxidative stress index in DETCA-treatment group. These results indicate that quercetin has antioxidant effect and protects NO from endogenous superoxide anion-driven inactivation and enhances its biological activity, suggesting that quercetin may scavenge superoxide anion in a Cu/Zn SOD, glutathione or ascorbic acid-inhibitable manner.     

The influence of vitamin E and methionine on the activity of enzymes and the morphological picture of liver of rats intoxicated with sodium fluoride

The aim of this study was to investigate the effects of vitamin E and methionine on the activity of enzymes regulating carbohydrate metabolism and enzymes associated with glutathione as well as to examine the morphology of the liver in rats exposed to sodium fluoride.The study was conducted in 18 male rats of Wistar strain. The rats were divided into three groups: a control group, which received distilled water and two experimental groups, which received sodium fluoride (10 mg/kg of body mass/24 h) in water solution. Animals in the second experimental group received 3 mg of vitamin E/rat/24 h and 2 mg methionine/rat/24 h. The experiment lasted 35 days. In supernatants obtained after homogenization of rat liver slices, the activity of the following enzymes was assayed: fructose-1,6-biphosphate aldolase (ALD) malate dehydrogenase (MDH), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH) the activity of glutathione peroxidase (GPx), glutathione transferase (GST) and glutathione reductase (GR). Pathomorphological evaluation was conducted on preparations made by standard paraffin method, followed by staining with hematoxylin and eosin. The administration of antioxidants counteracted changes in the activity of the enzymes and the morphological abnormalities of the liver induced by NaF. Antioxidants may be important in preventing toxicity of fluoride compounds.     

Hesperidin,a citrus bioflavonoid,alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster

Trichloroethylene (TCE) is a chlorinated organic pollutant of groundwater with diverse toxic effects in animals and humans. Here, we investigated the ameliorative role of hesperidin, a citrus bioflavonoid on TCE-induced toxicity in Drosophila melanogaster. Four groups of D. melanogaster (50 flies/vial, with 5 vials/group) were exposed to ethanol (2.5%, control), HSP (400 mg/10 g diet), TCE (10 μM/10 g diet) and TCE (10 μM/10 g diet) + HSP (400 mg/10 g diet) respectively in the diet for 5 days. Then, selected oxidative stress and antioxidant markers were evaluated. The results showed that TCE significantly increased the level of reactive oxygen species (ROS) and inhibited catalase, glutathione S-transferase and acetylcholinesterase (AChE) activities with concurrent depletion of total thiol level. However, co-administration of TCE and hesperidin mitigated TCE-induced depletion of antioxidants, and restored ROS level and AChE activity in the flies (p < 0.05). Overall, hesperidin offered protective potency on TCE-induced oxidative stress in the flies via anti-oxidative mechanism.     

Curcumin and β-caryophellene attenuate cadmium quantum dots induced oxidative stress and lethality in Caenorhabditis elegans model system

Curcumin (CUR) and β-caryophellene (BCP) are well known bioactive phytomolecules which are known to reduce oxidative stress in living organisms. Therefore, the present study was envisaged to explore the possible effects of CUR and BCP in suppression of cadmium quantum dots (CdTe QDs) induced toxicity in Caenorhabditis elegans. CdTe QD are luminescent nanoparticles extensively exploited for in vivo imaging, but long term bioaccumulation confer deleterious effects on living organisms. The 24-h LC₅₀ and LC₁₀₀ of CdTe QD were found to be 18.40 μg/ml and 100 μg/ml respectively. The CdTe QD exposure elevated HSP-16.2 expression mediating induction of the stress response. The CdTe QD lethality was due to increment in ROS and decline in SOD and GST expression. The present study demonstrates improved survival in BCP (50 μM) and CUR (20 μM) treated worms by over 60% (P < 0.01) and 50% (P < 0.029) in CdTe QD (100 μg/ml) exposed worms. Furthermore, BCP and CUR attenuate oxidative stress triggered by QD. The present study for the first time demonstrates CdTe QD toxicity remediation via BCP and CUR. The future investigations can unravel underlying protective effects of phytomolceules for remediating cyotoxicolgical effects of QDs.     

Effects of rifampin on CYP2E1-dependent hepatotoxicity of isoniazid in rats

Isoniazid and rifampin are first line drugs used to prevent and treat tuberculosis. The effects of rifampin co-administration on isoniazid-induced oxidative stress were investigated by the determination of the changes in hepatic metabolizing enzymes and DNA damage. Rats were treated with isoniazid alone (100 mg/kg, i.p.) or co-treated with rifampin (100 mg/kg, i.g.) for 10 or 21 days. Activities of CYP2E1, CYP1A1, CYP3A and glutathione S-transferases (GSTs) were analyzed by specific substrates. DNA oxidative damage by drug treatments was analyzed in precision-cut liver slices by HPLC–MS/MS. Isoniazid significantly increased CYP2E1 activities above control levels after 10 or 21 days treatment (2.25–4.59-fold), indicated by both chlorzoxazone hydroxylase and aniline hydroxylase (p < 0.01). Isoniazid treatment decreased activities of cytosolic total GST, alpha GST and mu GST after 21 days (p < 0.01). No change in activities of CYP1A1, CYP3A, and CYP3A1 mRNA expression was observed after isoniazid treatment. Rifampin co-administration significantly attenuated isoniazid-induced CYP2E1 levels (p < 0.01) and inhibition of mu GST (p < 0.01). Rifampin did not increase the formation of DNA adducts induced by isoniazid. These results suggest that rifampin co-administration does not increase isoniazid-induced oxidative stress through hepatic CYP2E1 during short-term treatment in experimental rats.