Determination of nephrotoxicity and genotoxic potential of silver nanoparticles in Swiss albino mice

Silver nanoparticles (AgNPs) possess properties that are important for industrial and medical applications. This study is aimed to investigate intra-peritoneal toxicity of AgNPs at 26, 52 or 78 mg/kg/day for 5 days in mice Swiss albino mice. The effects on oxidative stress markers activities of serum superoxide dismutase (SOD) and catalase (CAT), levels of serum glutathione (GSH), apoptosis (TUNEL assay), DNA strand breaks (comet assay) in lymphocytes, as well as histopathological of kidney tissue were determined. AgNPs significantly increased SOD and CAT activities reduced GSH levels. In kidney apoptosis (TUNEL assay) while DNA strand breaks (comet assay) in lymphocytes revealed that AgNPs at concentration 78 mg/kg produced significant apoptosis and DNA damage. AgNPs also produced associated histological renal tissue damage. Evidence suggests that AgNPs-mediated alterations may be attributed to oxidative stress.     

Oleuropein alleviates malathion-induced oxidative stress and DNA damage in rats

The effects of acute exposure to 250 mg/kg malathion and the protective effects of 20 mg/kg oleuropein, both administered intraperitoneally, were evaluated in Wistar male rats. Malathion administration increased malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, total oxidant status, and DNA damage, yet decreased total antioxidant activity, superoxide dismutase, and catalase activities in blood, liver, and kidney. Administration of oleuropein reversed malathion-induced oxidative stress, lipid peroxidation, DNA damage, and antioxidant enzyme activity.     

The effects of evening primrose oil on arsenic-induced oxidative stress in rats

Forty-eight male Wistar albino rats were allocated to the four groups such that each comprised 12 animals. The first group was maintained as the control. In group 2, evening primrose oil was administered at a dose of 0.1 mL rat^?1 day^?1 (～500 mg kg^?1 bw) into the stomach via gavage, whilst in group 3 sodium arsenide was administered at a concentration of 100 mg L^?1 in ad-libitum drinking water for 30 days. The fourth group was given 0.1 mL rat^?1 day^?1 evening primrose oil into the stomach via gavage plus 100 mg L^?1 of sodium arsenide in ad-libitum drinking water for 30 days. At the end of the 30th day, tissue (liver, lung, kidney, brain, heart, spleen, and testis) and blood samples were collected from each group. Malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in the samples. Exposure to arsenic in rats causes oxidative stress by increasing lipid peroxidation (increase of MDA and NO levels) and altering the activity of antioxidant enzymes. Evening primrose oil did not have any adverse effects. Furthermore, it was ascertained that the administration of arsenic with evening primrose oil reduced the severity of oxidative stress.     

Microwave-assisted synthesized zinc nanoparticles attenuate cisplatin-induced testicular toxicity in mice

Abstract

The purpose of this study was to investigate the protective effects of zinc nanoparticles against cisplatin-induced testicular toxicity in mice. Zinc nanoparticles were produced by microwave-assisted synthesis using Lavandula vera extract as reducing agent. Single doses of cisplatin (7?mg/kg, intraperitoneally) and ZnSO₄ (10?mg/kg, orally), and various doses of zinc nanoparticles (10???50?mg/kg, orally) and vitamin E (100?mg/kg, interaperitoneally) were administered. The protective role of zinc nanoparticles was determined biochemically and histologically. Gradual reduction in malondialdehyde levels and elevation in glutathione levels and in the activities of superoxide dismutase and catalase upon administration of zinc nanoparticles were observed. The pathology of mice treated with cisplatin/vitamin E and cisplatin/zinc nanoparticles were apparently equal, but vitamin E treatment was more effective in lowering oxidative stress markers than zinc nanoparticles. These findings suggest that co-administration of zinc nanoparticles with cisplatin could prevent adverse effects on the male reproductive system via their potential antioxidant properties.     

双酚A对小鼠肝脏和肾脏细胞的氧化损伤

为探究双酚A(BPA)的氧化毒性,分别以剂量为20、40和80mg·kg~(-1)·d~(-1)的BPA对雄性昆明小鼠灌胃处理1周,并测定了小鼠体内活性氧自由基(ROS)水平、还原型谷胱甘肽(GSH)含量、丙二醛(MDA)含量和DNA-蛋白质交联系数(DPC)。与对照组相比,各BPA暴露组小鼠肝脏和肾脏细胞中的ROS生成量、MDA含量和DPC系数均升高,而GSH含量下降(P<0.05或P<0.01)。ROS生成量、GSH含量和DPC系数均显示出剂量-效应关系。研究表明,BPA可扰乱小鼠肝脏和肾脏细胞的氧化应激平衡,诱导细胞氧化损伤。     

Lack of genotoxic potential of permethrin in mice evaluated by the comet assay and micronucleus test

Permethrin is a common insecticide that does not show genotoxic potential in standard in vitro and in vivo assays. To investigate the genotoxic potential of permethrin in more detail, two in vivo studies were conducted on female mice to assess DNA damage in tumor target organs by the comet assay and micronucleus test. For this, mice were administered permethrin at doses of 150, 300, or 600 mg/kg/day by gavage for 2 days, and their lung, liver, glandular stomach, peripheral blood, and bone marrow cells were examined for DNA damage. There were no significant increases in % tail DNA in the organs examined and no increase in micronuclei in peripheral blood by flow cytometry. Taken together, the present findings provide evidence that permethrin has no genotoxic, aneugenic, or clastogenic potential.     

In vitro assessment of genotoxic and oxidative effects of zinc borate

Zinc borate is used as flame retardant for plastics and cellulose fibers, paper, rubber, and textiles. Despite its wide industrial use, there is limited information concerning its toxicity. The aim of the present study was to investigate the concentration dependence (0–280 mg L^?1) of its genotoxic activity on cultured human lymphocytes by using sister chromatid exchange and chromosomal aberration assays. Total antioxidant capacity and the extent of oxidative stress were also determined. Zinc borate was found to be non-genotoxic at all tested concentrations. It exhibited antioxidant activity at concentrations lower than 40 mg L^?1, and total oxidative stress levels were not changed at any applied concentration of zinc borate.     

Toxicity of depleted uranium on isolated liver mitochondria: a revised mechanistic vision for justification of clinical complication of depleted uranium (DU) on liver

Depleted uranium (DU) is widely used in military anti-armor weapons. Recent evidence suggested that oxidative stress and mitochondrial dysfunction may contribute to DU-induced toxicity. However, the underlying mechanisms of DU toxicity in mitochondria are not well understood. In this study, liver mitochondria were obtained from Wistar rats treated with DU in the form of uranyl acetate (UA) (0.5, 1 or 2 mg/kg i.p.) using differential centrifugation. For in vitro experiments, control rat liver mitochondria were incubated with different concentrations of UA (50, 100 or 200 μM) for 1 hr. Mitochondrial reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential, and mitochondrial swelling were examined by flow cytometry. Mitochondrial sources of ROS formation were determined using specific substrates and inhibitors. Extent of lipid peroxidation (LPO) and glutathione (GSH) oxidation, and also complex II and IV activities were detected via spectroscopy. Further, the concentration of ATP and ATP/ADP ratio was measured using luciferase enzyme and release of cytochrome c from mitochondria which was detected by ELISA kit. UA induced succinate-supported mitochondrial ROS production, elevated LPO levels, GSH oxidation, and mitochondrial complex II inhibition. UA also induced mitochondrial permeability transition and increase in cytochrome c release which subsequently disturbed oxidative phosphorylation and reduced the mitochondrial ATP concentration. Data suggest that mitochondrial oxidative stress and uncoupling of oxidative phosphorylation may play key roles in DU-induced hepatic toxicity.     

Subacute chlorpyrifos-induced alterations in serum lipids and some oxidative stress biomarkers in male Wistar rats: beneficial effect of acetyl-L-carnitine

The present study evaluated the beneficial effect of acetyl-L-carnitine (ALC) on subacute chlorpyrifos (CPF)-induced alterations in serum lipid profiles and some biomarkers of oxidative stress in Wistar rats. Twenty-eight adult male rats divided into four groups of seven animals each (group I–IV) were used: I (S/oil) received soya oil (2 ml kg^?1), II (ALC) received ALC (300 mg kg^?1); III (CPF) received CPF (8.5 mg kg^?1 ～ 1/10th LD₅₀); IV (ALC+CPF) was pretreated with ALC (300 mg kg^?1) and then exposed to CPF (8.5 mg kg^?1), 30 min later. The treatment was orally for 28 days duration. Sera obtained from blood samples were evaluated for the levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and catalase (CAT). The levels of low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c), and atherogenic index (AI) were calculated. The result showed that elevated levels of TG, TC, LDL-c, VLDL-c, AI, and MDA, and the decreased levels of HDL-c, CAT, and SOD induced by CPF were modulated by ALC. It was concluded that ALC ameliorated the alterations in serum lipid and oxidative stress induced by CPF exposure in the rats, partly through its antioxidant properties.     

Cardioprotective effects of Commiphora mukul against isoprenaline-induced cardiotoxicity: a biochemical and histopathological evaluation

Commiphora mukul commonly known as Guggul is one of the oldest and commonly consumed herb for promoting heart and vascular health. Present study was undertaken to evaluate cardioprotective potential of Commiphora mukul against isoprenaline-induced myocardial necrosis in rats. Wistar albino rats were divided into three main groups: sham (saline only), isoprenaline control (saline and isoprenaline) and Commiphora mukul treated (Commiphora mukul and isoprenaline) groups. Commiphora mukul was administered in three doses 100, 200 and 400 mg kg(-1) p.o. for 30 days. On 29th and 30th day, the animals of isoprenaline control and Commiphora mukulpretreatment groups were administered isoprenaline (85 mg kg(-1); s.c.), consecutively at an interval of 24 hr. Isoprenaline administration produced a significant (p < 0.05) decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), reduced glutathione (GSH), and myocyte injury marker enzymes creatine-phosphokinase-MB (CK-MB) and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; malondialdehyde (MDA) in heart. Commiphora mukul pretreatment reversed the isoprenaline-induced oxidative changes in rat myocardium by significant (p < 0.05) increase in SOD, CAT, GSHPx, GSH and reduction of MDA. In addition to improving myocardial antioxidant status, Commiphora mukul also prevented the leakage of LDH and CK-MB from heart. Further, histopathological examination showed the reduction of necrosis, edema and inflammation following Commiphora mukul pretreatment. Based on present findings, it is concluded that Commiphora mukul may be a potential preventive and therapeutic agent against the oxidative stress associated ischemic heart disease owing to antioxidant and antiperoxidative activity.     

Oxidative stress and genotoxicity of 1-methyl-3-octylimidazolium chloride on loach (Misgurnus anguillicaudatus)

This study was a preliminary step to evaluate the acute toxicity of 1-methyl-3-octylimidazolium chloride ([C₈mim]Cl) on loach (Misgurnus anguillicaudatus) by determining the effects on hepatic antioxidant enzyme activities and by the comet assay. The results showed that [C₈mim]Cl had acute toxicity at concentrations above 20 mg L^?1, inducing oxidative stress and genotoxicity on fish liver cells. In respect to enzyme activities, [C₈mim]Cl induced changes in the activities of superoxide dismutase, catalase, and glutathione content the livers of fish exposed at 20–80 mg L^?1. [C₈mim]Cl at the same exposure level caused a remarkable increase in malondialdehyde level. The comet assay indicated that [C₈mim]Cl at 20–80 mg L^?1 induced genotoxicity in liver cells. With increased exposure concentration and time, the two comet parameters trailing rate and tail moment were significantly increased, with significant differences (P < 0.05) observed between control group and each treatment group. The present study shows that ionic liquids can be a threat to the health of aquatic organism when accidentally released to aquatic ecosystems.     

Effect of latex material on antioxidant enzymes,lipid peroxidation,DNA damage,and chromosomal aberration

Cell integrity is affected by oxidative stress when the production of active oxidants overwhelms antioxidant defense mechanisms. Latex, a natural polymer obtained from Hevea brasiliensis, is used in medical industry for manufacturing surgical gloves, urinary catheters, and dental dams. The aim of this study was to evaluate the effects of latex material on oxidative stress by in vivo and in vitro methods. In addition, the material was screened for its ability to induce any chromosomal aberrations (CAs) by in vitro method. In vivo studies were carried out with implanted latex material onto subcutaneous tissue of various batches of experimental Wistar rats. At the end of experimental period, animals were anesthetized, blood was collected for serum analysis, and sacrificed. Liver was excised for the determination of antioxidant enzymes and lipid peroxidation (LPO). Subcutaneous tissues were obtained for the extraction of genomic DNA from implanted animals and checked for the presence of 8-hydroxy-2-deoxyguanosine (8-OHdG), considered an indicator of DNA damage. Simultaneously, in vitro studies were carried out using fresh liver and subcutaneous tissue obtained from Swiss albino mice treated with physiological saline extract of latex material. For the estimation of both in vitro and in vivo oxidative stress, 10% liver homogenate was assessed for stress indicators like reduced glutathione, glutathione reductase, glutathione peroxidase, LPO and protein content. The results of both in vivo and in vitro studies indicated that the chemical leachents from the latex material did not significantly affect LPO and the levels of antioxidant enzymes. There was also no significant increase in 8-OHdG content due to the presence of implanted latex material. Finally, the results of in vitro CA test and G banding indicated that extracts of test material did not induce any chromosomal abnormalities.     

Effects of subchronic exposure to carbofuran on antioxidant defence system and malondialdehyde levels in common carp (Cyprinus carpio L.)

The present study focused on the assessment of oxidative stress induction by pesticides such as carbamates which are widely used as insecticides and nematicides and contaminate aquatic ecosystems on certain biomarkers in liver of common carp (Cyprinus carpio L.). Biomarkers selected for stress monitoring were malondialdehyde (MDA), an index of lipid peroxidation, and antioxidant defence system enzymes, mainly catalase (CAT), glutathione reductase (GR), and glutathione-S-transferase (GST) activities in liver of fish exposed to 0, 10, 50, or 100?µg?L^?1 of carbofuran for 4, 15, or 30 days. Oxidative stress was found in liver of common carp exposed to carbofuran which was manifested by a decrease in CAT and GR activities after 4 and 30 days of exposure. An adaptive response was probably produced since at day 15 no modifications in the CAT activity and increased GR activity were observed. In addition, a decrease in MDA content with the highest concentration of carbofuran used was found after 30 days of exposure. However, no significant changes were found in GST activity showing a varied response. The results concerning oxidative and antioxidant profiles indicate that subchronic exposure to the insecticide carbofuran is capable of inducing oxidative stress in fish.     

Inhibition of cyclooxygenase-2 protects against cocaine hepatotoxicity in CF-1 mice

Gender differences in oral cocaine hepatotoxicity have been observed and lipopolysaccharide (LPS) was shown to potentiate cocaine hepatotoxicity in male CF-1 mice. Since cocaine and LPS inflict hepatocellular damage through the production of harmful reactive species, the role of cyclooxygenase-2 (COX-2) in gender-dependent cocaine hepatotoxicity was investigated. COX-2 increases nitric oxide (NO) synthesis and pro-inflammatory mediator production in response to hepatocellular insult. Male and female CF-1 mice were orally administered 20 mg kg^?1 cocaine hydrochloride once daily for 7 days. Four hours after the last cocaine administration, the mice received 12 × 10⁶ EU LPS intraperitoneally (cocaine + LPS). Mice receiving meloxicam (7.5 mg kg^?1, p.o.), a selective COX-2 inhibitor, were pretreated 1 h before each cocaine administration. Meloxicam prevented liver damage in males produced by cocaine and cocaine + LPS as evidenced by microscopic appearance and biochemical indices equivalent to saline treatment. Acetaminophen (APAP) was administered orally as a positive control which shows no gender dependency and elicited a hepatotoxic response in both males and females. Altered biochemical indices suggest that COX-2 is activated, possibly to a greater extent in females versus males in APAP-induced hepatotoxicity. Meloxicam prevented all oxidative stress changes induced in males following APAP. The results suggest that the induction of COX-2 is responsible, in part, for cocaine hepatotoxicity with and without LPS exposure in male mice.     

甲醛暴露时间延长加剧小鼠哮喘模型肺氧化损伤并促进IL-17表达

为了探究不同暴露时间甲醛对小鼠哮喘模型肺氧化应激及IL-17表达的影响,用浓度为3.0 mg·m~(-3)的甲醛气体吸入染毒,同时将48只雄性Balb/c小鼠随机分为6组:(1)对照组(生理盐水组);(2)ovalbumin(OVA)致敏组;(3)0.5 h甲醛+OVA组;(4)1h甲醛+OVA组;(5)1.5 h甲醛+OVA组;(6)2 h甲醛+OVA组,以不同时间长度进行甲醛暴露,连续35 d。OVA致敏组、0.5 h甲醛+OVA组、1 h甲醛+OVA组、1.5 h甲醛+OVA组、2 h甲醛+OVA组均在第11、18及25天腹腔注射OVA致敏液(5 mg OVA+175 mg Al(OH)_3+30 mL生理盐水),第29~35天(共计1周)进行1%OVA雾化(30 min·d~(-1)),每日1次,诱发哮喘。第36天进行以下操作:取肺组织测定肺系数并制作肺匀浆,检测肺组织中活性氧自由基(ROS)、丙二醛(MDA)和还原型谷胱甘肽(GSH)的含量,并采用ELISA法检测肺组织中IL-17的水平。同时,采用HE染色法观察小鼠肺部气道的病理学变化。结果显示,在浓度为3.0 mg·m~(-3)的甲醛气体吸入染毒条件下,与对照组相比,1.5 h甲醛+OVA染毒组、2 h甲醛+OVA染毒组ROS、MDA、IL-17含量上升,具有统计学意义(P0.01)。同时,随着暴露时间长度的增加,小鼠肺部气道出现明显病理学变化。综上所述,每天2 h甲醛+OVA染毒能对小鼠肺造成损伤并恶化OVA对小鼠肺的损伤,产生炎症反应,并通过氧化应激反应介导。     

Hepatoprotective activity of 1-(4-(Dimethylamino)Benzylidene)-5-(2-Oxoindolin-3-ylidene) Thiocarbohydrazone in rats

The aim of the present study was to evaluate the hepatoprotective activity of 1-(4-(dimethylamino)benzylidene)-5-(2-oxoindolin-3-ylidene) thiocarbohydrazone, a novel isatin derivative against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Hepatic damage was induced by administration of CCl₄ (1 ml/kg, b.w., p.o.) in combination with liquid paraffin (1:1) as a single dose. The hepatotoxic rats were treated with test compound at doses of 50 or 100 mg/kg for three days and liver damage biomarkers, including activities of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP), and levels of total serum bilirubin (TB) measured in blood samples. Results demonstrated that treatment with test compound at doses of 50 or 100 mg/kg to hepatotoxic rats produced a significant dose-dependent reduction of elevated SGOT, SGPT, ALP activities and TB levels indicating a hepatoprotective effect that was confirmed by histopathological examination of liver tissues. The study results confirmed the hepatoprotective activity of 1-(4-(dimethylamino)benzylidene)-5-(2-oxoindolin-3-ylidene) thiocarbohydrazone in rats.     

Toxicity of nano-anatase TiO2 to mice: Liver injury,oxidative stress

There are concerns regarding the toxicity of nano-TiO₂, but data are limited on the mechanism underlying oxidative damage to liver of mice. In order to further study these mechanisms of nano-TiO₂ particles, nano-anatase TiO₂ (5 nm) were injected into the abdominal cavity of ICR mice daily for 14 days and biochemical parameters in liver were investigated. The increase of hepatic lipids peroxide produced by nano-anatase TiO₂ suggested an oxidative attack that was activated by a reduction of antioxidative defense mechanisms as measured by analyzing the activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione peroxidase, as well as antioxidant levels such as glutathione and ascorbic acid. The antioxidative responses of liver were reduced in mice by nano-anatase TiO₂. The oxidative stress of nano-anatase TiO₂ on liver was greater than that seen with bulk-TiO₂.     

Effect of repeated oral administration of bifenthrin antioxidant status and acetylcholinesterase activity in brain of rats

The oxidative-stress-inducing potential of the pyrethroid, bifenthrin, in the brain of rats was evaluated following daily oral administration of 5.8 mg/kg body weight. Lipid peroxidation in the brain was increased, while the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase decreased. The activity of acetylcholinesterase (AChE) in erythrocytes and brain also decreased. Bifenthrin induces severe oxidative stress in brain, and inhibits brain and erythrocyte AChE.     

Cadmium accumulation in <Emphasis Type="Italic">Panax notoginseng</Emphasis>: levels,affecting factors and the non-carcinogenic health risk

Cadmium (Cd) contamination has been reported to be a problem for the safe usage of Panax notoginseng (Sanchi); thus, it is necessary to elucidate the Cd accumulation in Sanchi and to assess its associated health risk. Samples were collected from major producing areas in Yunnan, China. The average concentration of Cd in Sanchi was 0.43 mg/kg, which exceeds the standard level for herbal medicine in China (0.3 mg/kg). A stepwise regression analysis showed that zinc and the pH were the related factors that most significantly impacted Cd in Sanchi roots. The hazard quotient values were estimated as 0.0010 (men) and 0.0012 (women) for consumers taking preparations and were 0.011 (men) and 0.013 (women) for consumers taking health products, implying that there is no non-carcinogenic hazard associated with Sanchi consumption. However, a Monte Carlo simulation showed that approximately 0.80 % of male and 1.02 % of female consumers via drug consumption and 36.28 % of male and 41.87 % of female consumers via health product consumption had an exposure exceeding the acceptable daily intake (ADI) of Cd from drugs (1 % of the total oral ADI as suggested by the World Health Organization). These people should control their oral Cd intake from both Sanchi consumption and diet as a whole.