Lack of reversal of oxidative damage in renal tissues of lead acetate‐treated rats

Removal of lead from the environment of man or otherwise, the movement of man from lead‐contaminated areas has been employed as a means of abatement of the toxic effects of lead. Whether toxic effects in already‐exposed individuals subside after lead withdrawal remains unanswered. To understand the reversibility of nephrotoxicity induced by lead acetate, male Wistar rats were orally exposed to 0.25, 0.5, and 1.0 mg/mL of lead acetate for 6 weeks. Activities of glutathione‐s‐transferase, catalase (CAT), superoxide dismutase (SOD) and the concentrations of hydrogen peroxide (H₂O₂), and malondialdehyde increased significantly (p < 0.05) in a dose‐dependent manner, whereas reduced glutathione (GSH) level and glutathione peroxidase activity were significantly reduced. The pattern of alterations in most of the oxidative stress and antioxidant parameters remained similar in rats from the withdrawal period, although CAT and SOD activities reduced, in contrast to their elevation during the exposure period. Serum creatinine levels were significantly elevated in both exposure and withdrawal experiments whereas serum blood urea nitrogen levels were not significantly different from the control in both exposure and withdrawal periods. The histological damage observed include multifocal areas of inflammation, disseminated tubular necrosis, and fatty infiltration of the kidney tubules both at exposure and withdrawal periods. The results suggest that lead acetate‐induced nephrotoxicity by induction of oxidative stress and disruption of antioxidant. The aforementioned alterations were not reversed in the rats left to recover within the time course of study. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1235–1243, 2015.     

Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods

This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity.     

The effect of lovastatin on oxidative stress and antioxidant enzymes in hydrogen peroxide intoxicated rat

Oxidative stress has been linked to the development of many diseases and hastens the progression of cardiovascular diseases. Since lovastatin is used worldwide as a cholesterol lowering drug, the present study was undertaken to evaluate the antioxidant property of lovastatin against H₂O₂ induced oxidative stress in rats. Four study groups of rats of four animals each were treated with DMSO (control), H₂O₂ (OS), lovastatin (L) and H₂O₂ + lovastatin (OSL). On the 15th day the animals were sacrificed, and the liver and heart tissues were analyzed for oxidative stress biomarkers and anti-oxidant enzymes. Results of the OSL-group showed a reduction in thiobarbituric acid reactive substances in liver (42.7%) and heart tissue (8%) compared with the control group. An increase was observed in the activity of the antioxidant enzymes, catalase (34.6% in liver and 33.3% in heart) and glutathione peroxidase (50.5% in liver and 34.7% in heart). A commensurate increase in the activity of G6PDH was observed indicating an enhanced requirement of NADPH. The ratio GSH:GSSG in liver (1.05) and heart (0.84) was satisfactorily regulated compared to the control group (1.01 in liver and 0.93 in heart). These results suggest that lovastatin possesses antioxidant activity and reduces oxidative stress.     

2型糖尿病大鼠主动脉内皮细胞氧化损伤及缬沙坦的保护作用

目的探讨2型糖尿病大鼠氧化应激与主动脉内皮细胞损伤的关系,观察缬沙坦对两者的影响。方法SD大鼠,用长期高能量饮食加小剂量注射链脲佐菌素(STZ)的方法复制模型。注射STZ12wk末,将大鼠分为3组:正常组、糖尿病组、缬沙坦治疗组(24mg·kg-1·d-1,灌胃给药8wk)。在注射STZ12和20wk末,检测大鼠的内皮依赖性血管舒张反应及主动脉内皮形态,血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)和一氧化氮(NO)含量,以及主动脉一氧化氮合酶(NOS)基因表达情况。结果①12wk末,糖尿病大鼠主动脉对低浓度乙酰胆碱(ACh)舒张反应减弱,局部内皮隆起,血清SOD、GSH-Px活性增强,MDA和NO含量增加,主动脉iNOS mRNA表达明显上调,eNOS mRNA表达无明显改变。②20wk末,糖尿病大鼠主动脉对各浓度ACh的反应性均减弱,主动脉内皮变性、坏死,血清SOD、GSH-Px活性减弱,MDA含量进一步增加,NO含量下降,主动脉iNOS mRNA表达仍升高,eNOS mRNA表达降低,缬沙坦治疗后能减轻主动脉病变,改善血清SOD、GSH-Px、MDA、NO及主动脉NOS mRNA表达的异常。结论糖尿病大鼠的氧化应激和NO系统的紊乱参与了主动脉病变过程,增强机体抗氧化能力及调节NO生成可能是缬沙坦发挥主动脉保护作用的机制之一。     

Protective effect of artichoke (Cynara scolymus) leaf extract against lead toxicity in rat

Abstract

Context: Artichoke, Cynara scolymus L. (Asteraceae), has many natural antioxidants and multiple pharmacological actions. Recent studies have shown that it has antitoxic activity.

Objective: Lead (Pb) is a dangerous environmental toxicant that induces a broad range of dysfunctions in human. This study evaluated the protective effect of the hydroethanolic extract of artichoke against altered biochemical parameters in rats fed with lead-containing diet.

Materials and methods: Thirty-two rats were randomly divided into four groups. The first (control) group received standard diet. The second, third and fourth groups received 500?mg lead/kg diet, 500?mg lead/kg diet plus 300?mg/kg b.w. artichoke extract daily, and 500?mg lead/kg diet plus 1?mg vitamin C/100?g b.w. daily for 6 weeks, respectively. Serum lead, lipoprotein profile, ALT (alanine transaminase), AST (aspartate transaminase), ALP (alkaline phosphatase), malondialdehyde (MDA) and liver histopathology assessments were conducted.

Results: Serum lead, triglyceride (TG), VLDL, ALT, AST, ALP and MDA levels decreased significantly (p?<?0.05) in the artichoke-treated group (35.85, 38.26, 38.38, 21.90, 12.81, 26.86 and 46.91%, respectively) compared to lead-intoxicated rats without treatment. No significant change was observed in serum lead, ALP and ALT between artichoke and vitamin C-treated groups (p?>?0.05). Furthermore, the liver histopathology in rats treated with artichoke showed a mild degree of lymphocyte infiltration that was relatively comparable to the control and vitamin C-treated groups.

Discussion and conclusion: These results clearly show that the artichoke extract in lead-poisoned rats has suitable chelating properties for the reduction of blood lead levels.     

Phytochemical,antioxidant and protective effect of cactus cladodes extract against lithium-induced liver injury in rats

Context: Opuntia ficus-indica (L.) Mill. (Castaceae) (cactus) is used in Tunisian medicine for the treatment of various diseases.

Objective: This study determines phytochemical composition of cactus cladode extract (CCE). It also investigates antioxidant activity and hepatoprotective potential of CCE against lithium carbonate (Li₂CO₃)-induced liver injury in rats.

Materials and methods: Twenty-four Wistar male rats were divided into four groups of six each: a control group given distilled water (0.5?mL/100?g b.w.; i.p.), a group injected with Li₂CO₃ (25?mg/kg b.w.; i.p.; corresponding to 30% of the LD₅₀) twice daily for 30 days, a group receiving only CCE at 100?mg/kg of b.w. for 60 days and then injected with distilled water during the last 30 days of CCE treatment, and a group receiving CCE and then injected with Li₂CO₃ during the last 30 days of CCE treatment. The bioactive components containing the CCE were identified using chemical assays.

Results: Treatment with Li₂CO₃ caused a significant change of some haematological parameters including red blood cells (RBC), white blood cells (WBC), haemoglobin content (Hb), haematocrit (Ht) and mean corpuscular volume (VCM) compared to the control group. Moreover, significant increases in the levels of glucose, cholesterol, triglycerides and of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities were observed in the blood of Li₂CO₃-treated rats. Furthermore, exposure to Li₂CO₃ significantly increased the LPO level and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the hepatic tissues.

Conclusion: CCE possesses a significant hepatoprotective effect.     

Nephrotoxic effects of lead nitrate exposure in diabetic and nondiabetic rats: Involvement of oxidative stress and the protective role of sodium selenite

Heavy metals are known to be toxic to organisms. The present study was undertaken to evaluate the protective effect of sodium selenite against lead nitrate (LN)‐induced nephrotoxicity in diabetic and nondiabetic rats. Animals were divided into eight groups where the first was served as a control, whereas the remaining groups were treated with sodium selenite (1 mg/kg b.w.), LN (22.5 mg/kg b.w.) and a combination of LN and sodium selenite and diabetic forms of these groups. Changes in antioxidant enzyme activities, malondialdehide levels, serum urea, uric acid, creatinine levels, body, and kidney weights and histopathological changes were determined after 28 days. LN caused severe histopathological changes, increment in urea, uric acid, creatinine, and MDA levels, also decreasing in antioxidant enzyme activities, body, and kidney weights. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Also diabetes caused alterations on these parameters compared with nondiabetic animals. We found that sodium selenite did not show protective effect on diabetes caused damages. As a result, LN caused nephrotoxicity and sodium selenite alleviated this toxicity but sodium selenite did not protect kidneys against diabetes mediated toxicity. Also, LN caused more harmfull effects in diabetic groups compared with nondiabetic groups. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1229–1240, 2016.     

Protective effect of Aquilegia vulgaris (L.) against lead acetate-induced oxidative stress in rats

Oxidative stress has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activity of the ethanol extract of Aquilegia vulgaris (L.) against lead acetate (LA)-induced oxidative stress in male rats. Tested animals were treated orally with A. vulgaris extract (100 ppm) in combination with, before, or after LA treatment (20 ppm). The results indicated that the extract alone did not induce any significant changes in body weight gain, food intake, serum biochemical chemistry or the histological picture of the liver and kidney. However, it increased significantly the level of Glutathione (GSH). On the other hand, LA decreased food intake, body weight gain and induced oxidative stress as indicated by the significant changes in serum biochemical parameters and histological picture of liver and kidney and increased lipid peroxide and reduces GSH levels in liver tissues. The extract succeeded to improve the histological pictures of liver and kidney and the biochemical parameters towards the normal values of the control. Moreover, this improvement was pronounced in the animals treated with the extract after LA intoxication.     

Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain

This study is intended to determine the effect of lead acetate on glutathione and its associated enzymes of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks and parallel controls were maintained. They were sacrificed at the first, fourth and eighth week to isolate whole brains, which were separated into cerebellum, hippocampus, frontal cortex and brain stem. The data indicate enhanced (P < 0.05) glutathione peroxidase (G‐Px) activity at most of the intervals for cerebellum, frontal cortex and brain stem, suggesting conversion of GSH to GSSG, while the hippocampus showed decreased levels. In contrast, glutathione reductase (GR) decreased significantly (P < 0.05) in cerebellum, frontal cortex and brain stem at all intervals except the fourth week in frontal cortex and brain stem. Hippocampus exhibited a gradual and significant (P < 0.05) increase in GR activity. Glutathione‐S‐transferase (GSTase) activity increased with exposure time in all four brain tissues, showing protection against lead acetate toxicity. The GSH and GSSG levels correlated well with the activities of GPx, GR and GSTase in all four regions of the brain. Overall the results indicate that lead acetate affects glutathione‐related enzymes differentially and these changes can be attributed to differences in tissue susceptibility. Copyright © 2009 John Wiley & Sons, Ltd.     

Comparison of the developmental milestones and preweaning neurobehavioral parameters in rat pups exposed to lead (Pb) during gestation,lactation and pregestation period

Studies in urban children exposed to low lead (Pb) have shown neurobehavioral deficits in the domains of intelligence, reaction time and attention. The structures – hippocampus (vital for learning and memory) and cerebellum (play a role in motor behavior and cognition) – which develop postnatally, are affected by developmental Pb exposure. The effect of low level of Pb exposure during specific periods of early brain development on early neurobehavioral outcomes in rat pups has not been studied. So in this study, pregnant albino Wistar strain rats were exposed to low levels of Pb in drinking water during gestation period (G group), lactation period (L group), both gestation and lactation period (GL group) and prior to pregnancy (a period of 1 month) (PG group). The rat pups born in each of these groups were assessed in preweaning neurobehavioral parameters including surface righting reflex, swimming development, negative geotaxis and ascending wire mesh test. The swimming development scores were low in the GL group of rats. The negative geotaxis score in GL and G groups were altered. The day of achievement of ascending wire mesh test was significantly delayed in GL, G and L groups of rats. To conclude, results show that (a) low level of Pb exposure during gestation and lactation period of brain development causes significant alterations in the early neurobehavioral and sensorimotor reflex development in the absence of concomitant weight loss and (b) gestation period only and lactation period only, Pb exposure causes alteration in some of the neurobehavioral outcomes.     

The effect of adrenomedullin on rats exposed to lead

Adrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The antioxidative properties of AdM have been reported recently. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by stressors. Lead, commonly detected in air, soil, water and food, is a major source of oxidative stress. The effect of AdM in the liver of rats exposed to lead was investigated. Twenty-four female Wistar rats were divided into four groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead + adrenomedullin (Pb + AdM) group. In the Pb-treated groups, the animals were exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1) body weight) in the third week of lead treatment for 1 week. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were determined in the liver of rats. Histological changes in the liver were examined by light and electron microscopy as well. The MDA levels were increased significantly in the Pb-treated groups, but in the Pb + AdM group the MDA levels were decreased significantly when compared with the Pb group. AdM reduced hepatic damage in the Pb + AdM group, but the difference in the total histopathological scores between the Pb and Pb + AdM groups was not significant. When the results are taken together, it can be concluded that AdM may have protective or compensating effects in lead toxicity.     

Effects of low-level lead exposure on blood pressure and function of the rat isolated heart

Objective:

Exposure to low levels of lead acetate can induce hypertension in both humans and experimental animals. The exact mechanisms of lead-induced hypertension are not well understood, but its pathogenesis could be explained by the changes in heart rate and contractility.

Materials and Methods:

In the present study, the effects of exposure to 100 ppm of lead in drinking water (for periods of 4, 8, and 12 weeks) on blood pressure and some physiologic parameters (eg, electrocardiography [ECG], heart rate [HR], cardiac contractility, and coronary flow) of isolated beating rat heart was investigated using the Langendorff isolated heart apparatus. The isolated hearts were perfused with Krebs-Henseleit solution (37°C; pH 7.4; gassed with 95% O₂ + 5% CO₂). All data were digitized by a software program for further analysis.

Results:

The blood pressure in the 8- and 12-week lead-exposed groups was significantly increased as compared to the control group. The ECG showed arrhythmias and conduction abnormalities only in the late phases of exposure (12 weeks). The HR and contractility were significantly higher in the 8- and 12-week lead-treated rats but not in the 4-week group. No significant changes were observed in coronary flow.

Conclusion:

These results indicate that: 1) low levels of lead exposure do not significantly affect the ECG in the early phase, 2) low levels of lead exposure causes ECG changes in the late phases of exposure, and 3) this level of lead exposure can increase HR and cardiac contractility but has no effect on coronary flow.     

Evaluation of protective effect of rutin on lead acetate-induced testicular toxicity in Wistar rats

In this study, the effect of rutin (RT) was investigated on lead-induced testis tissue damage in rats. Oral administration of rutin (50?mg/kg) effectively inhibited the levels of marker enzymes and antioxidant enzymes as compared with lead acetate-treated group. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and histopathological changes of testes were investigated. Lead acetate decreased the levels of SOD, CAT, GPx, and GST compared with the control group. Light microscopic analyses revealed that lead acetate induced several histopathological changes in testis tissue. In the RT-treated group, there were statistically significantly decreases in antioxidant enzyme activities and pathological changes in the tissue. The results suggest that RT possesses significant potential in reduced lead acetate-induced testicular toxicity.     

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

The effect of combined treatment with meso-2,3-dimercaptosuccinic acid (DMSA) and calcium supplementation in reducing lead absorption and enhancing lead elimination was evaluated in suckling rats under two experimental conditions: during ongoing oral lead exposure (lead acetate, 2 mg Pb kg(-1) day(-1), total dose 16 mg Pb kg(-1)) or after lead exposure (72 h after a 2-day lead exposure, total dose 12 mg Pb kg(-1) s.c.). The artificial feeding method was used for calcium supplementation, with 6% Ca (as CaHPO(4)) suspension in cow's milk to increase the daily calcium intake about three times above control values. Artificial feeding lasted for 7 h a day over eight consecutive days. During this period DMSA was administered on 6 days twice a day (0.5 mmol kg(-1) day(-1) p.o.). At the end of the experiments, Pb, Ca and Zn in the carcass and Pb, Fe and Cu in the liver, kidneys and brain were analysed by atomic absorption spectrometry. Calcium supplementation during lead exposure reduced tissue lead but had no effect when applied after lead exposure, and DMSA administered either during or after lead exposure lowered the tissue lead. Combined treatment during ongoing lead exposure caused a greater reduction in tissue lead than either DMSA or calcium treatment alone. When administered after lead exposure, it had no advantage over DMSA treatment alone but did not impair its efficacy. Combined treatment had no influence on growth and did not seriously disturb essential element status. It is concluded that calcium supplementation could be applied during DMSA therapy, when indicated.     

Influence of iron on modulation of the antioxidant system in rat brains exposed to lead

The objective of this study was to evaluate markers of oxidative stress in the brains of rats exposed to lead acetate (Pb(C₂H₃O₂)₂), either associated or not associated with ferrous sulfate (FeSO₄). A total of 36 weaning rats (Rattus norvegicus) were divided into 6 groups of six animals and exposed to lead acetate for six weeks. In the control group (control), the animals received deionized water. The Pb260 and Pb260 + Fe received 260 µM lead acetate, and the Pb1050 and Pb1050 + Fe received 1050 µM lead acetate. The Pb260 + Fe and Pb1050 + Fe were supplemented with 20 mg of ferrous sulfate/Kg body weight every 2 days. Group Fe received deionized water and ferrous sulfate. The rat brains were collected to analyze the enzymatic activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the concentration of reduced glutathione (GSH), lipid peroxidation (TBARS), and total antioxidant substance (TAS) (DPPH^? technique). The activity of SOD and GPx in the experimental groups decreased compared to the control, together with the concentration of GSH (p < 0.05). For CAT analysis, SOD tended to increase in concentration in the experimental groups without a concomitant exposure to FeSO₄, whereas GPx showed a slight tendency to increase in activity compared to the control. For TAS‐DPPH^?, there was a decrease in the experimental groups (p < 0.05). According to the results, SOD, GPx, and GSH were affected by lead acetate and exposure to ferrous sulfate changed this dynamic. However, further studies are needed to verify whether ferrous sulfate acts as a protectant against the toxic effects of lead. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 813–822, 2017.     

Response of antioxidant enzymes in coontail (Ceratophyllum demersum L.) plants under cadmium stress

Cadmium (Cd) contamination of aquatic systems is of major concern since it is a nonessential element and hampers plant growth upon accumulation. The aim of this study was to investigate the Cd accumulation behavior of coontail plant, Ceratophyllum demersum L., toxicity induced and response of the antioxidant system. Plants were exposed to various concentrations of Cd (0-10 microM) for a period of 1-7 days. Accumulation of Cd was found to be a concentration duration dependent phenomenon. The maximum accumulation of Cd, 1293 microg g(-1) dw, was observed after 7 days at 10 microM. Plants showed significant stimulation of the activities of various antioxidant enzymes viz., superoxide dismutase (EC 1.15.1.1), ascorbate peroxidase (EC 1.11.1.11), guaiacol peroxidase (EC 1.11.1.7), catalase (EC 1.11.1.6), and glutathione reductase (EC 1.6.4.2) and tolerated toxicity of Cd up to moderate concentration of 5 microM. At 10 microM exposure, enzyme activities declined and plants experienced toxicity, which was evident by the significant decrease in the photosynthetic pigments and by increase in the levels of H(2)O(2), lipid peroxidation and ion leakage. In conclusion, modulation of antioxidant system in a coordinated manner in response to Cd accumulation appears to help plants tolerate toxicity of Cd up to 5 microM.     

丹酚酸A对大鼠脑突触体和线粒体氧应激损伤的体外保护作用

利用蔗糖梯度法分离大鼠脑突触体和线粒体，以Fe^2＋-半胱氨酸（Cys）为氧自由基生成系统造成大鼠脑突触体和线粒体氧应激损伤模型. 在体外Fe^2＋-Cys与脑突触体和线粒体共同温孵可使丙二醛(MDA)生成量显著增加，线粒体ATP酶活性下降. 预先加入丹酚酸 A(Sal A)可显著抑制MDA生成，恢复线粒体 ATP酶活性，防止线粒体肿胀和膜流动性的降低. 通过电镜照片可看到Fe^2＋-Cys引起的线粒体和突触体结构病理性改变，预先加入Sal A可减轻Fe^2＋-Cys造成的这一损伤. 此外，Sal A可阻抑H₂O₂引起的脑突触体GSH含量的降低. 由此可见，Sal A体外对氧应激引起的大鼠脑突触体和线粒体脂质过氧化损伤有明显的保护作用.     

Blood thioredoxin reductase activity,oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead‐exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ‐aminolevulinate dehydratase (δ‐ALA‐D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ‐ALA‐D activity was inhibited only in battery workers, whereas the δ‐ALA‐D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = ?0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione‐S‐transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead‐ and cadmium‐exposed populations. However, lead‐associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re‐evaluating the recommended health‐based limits in occupational exposure to this metal. Copyright © 2011 John Wiley & Sons, Ltd.     

Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats

Lead acetate (PbA) is one of the major environmental contaminants with grave toxicological consequences both in the developing and developed countries. The liver and erythrocyte antioxidant status and markers of oxidative were assessed. Exposure of rats to PbA led to significant decline (p < 0.05) in hepatic and erythrocyte glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) content. Similarly, malondialdehyde (MDA) and H₂O₂ concentrations were significantly (p < 0.05) elevated. Histopathology and immunohistology of liver of rats exposed to PbA showed focal areas of necrosis and COX-2 expression after 6 weeks of PbA withdrawal. Taken together, hepatic and erythrocytes antioxidant defence system failed to recover after withdrawal of the exposed PbA for the period of the study. In conclusion, experimental animals exposed to PbA did not recover from hepatotoxicity and disruption of erythrocyte antioxidant defence system via free radical generation and oxidative stress.