An improved model of lead-induced brain dysfunction in the suckling rat

Experimental lead encephalopathy is produced in suckling rats when lead is added to the mother's diet. Lead passes into developing sucklings via maternal milk. Lead-poisoned newborns have been reported to exhibit pronounced retardation of growth and during week 4 of life develop paraplegia and extensive histologic lesions of the cerebellum. Under similar dietary conditions experimental lactating rats eat 30% less food than controls, resulting in: (a) sustained loss in body weight of nursing mothers and (b) offspring who develop paraplegia and cerebellar damage after gaining access to the maternal lead-containing diet.We have found that a lactating mother rat consuming 5% lead acetate (PbAc) in the diet (2.73% Pb) produced milk containing 25 ppm lead. When the diet of the mother is changed on day 16 from 5% PbAc to one containing 25 ppm Pb, and neonates are allowed free access to the same solid diet, the sucklings still have retarded body growth but do not develop paraplegia or grossly apparent vascular damage of the cerebellum. However, during week 4 these animals exhibit hyperactivity, tremors, and stereotype behavior. Pair-fed controls coetaneous to experimental groups do not display such activities. The severe paraplegia and histopathologic lesions reported by others in the older model obscures minimal brain dysfunction. We propose the present procedure as a model for studies of the subtle effects of lead on the central nervous system.     

Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid

Objective: The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. Methods: The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead – Ascorbic Acid (Lead-AA), (4) Lead – Garlic (100?mg/kg, daily, gavage) (Lead-Gar). Results: In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. Conclusion: It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.     

Ameliorative effect of sesame lignans on nicotine toxicity in rats

Nicotine causes oxidative and genotoxic damages in the tissues leading to several diseases. Any strategy through natural diet that prevents or slows the progression and severity of nicotine toxicity has a significant health impact. This work is designed to investigate natural antioxidants that play effective protective role against nicotine-induced toxicity. Experiments were conducted on male albino rats by injecting nicotine tartrate (3.5 mg/kg body wt./day for 15 days) subcutaneously and thereby supplementing sesame lignans (0.1 g/100 g diet and 0.2 g/100 g diet) orally to them. Significant (P < 0.01) increase of total cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol, decrease of HDL-cholesterol, decrease in antioxidant enzymes and increase in concentration of lipid peroxidative product has been observed in plasma due to nicotine toxicity. Significant (P < 0.01) decrease of total DNA contents and highly significant (P < 0.001) DNA damage of liver tissue is also observed on nicotine treatment. Sesame lignans minimizes the above mentioned effects. The nicotine-induced oxidative and genotoxic damages on the tissues can be effectively attenuated by sesame lignans supplemented diet.     

Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment

We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5 mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.     

Ebselen and diphenyl diselenide do not change the inhibitory effect of lead acetate on delta-aminolevulinate dehidratase

It is known that lead is toxic to several species of animals, and growing data support the participation of oxidative in lead toxicity. Selenium compounds, like diphenyl diselenide and Ebselen have a thiol-peroxidase like and other antioxidant properties. In this work, we determine whether these non-thiol-containing compounds with antioxidant properties could reverse the toxicity produced by Pb(2+). Lead acetate injection followed by injection with Ebselen or diphenyl diselenide did not change the levels of non-protein thiol groups (NPSH), whereas simultaneous treatment with lead plus Ebselen reduced NPSH levels in liver. Lead and Ebselen caused a marked reduction in TBARS level in kidney, whereas lead or selenium compounds did not change TBARS levels in brain or liver. Lead acetate inhibited, δ-aminolevulinate dehydratase (ALA-D) activity in blood, liver, kidney and brain. Selenium compounds did not change enzyme activity nor the inhibitory effect of lead acetate in kidney and liver. Ebselen reversed brain ALA-D inhibition caused by Pb(2+). Reactivation index for ALA-D by DTT was higher in lead-treated groups than control groups in all tissues. Lead acetate or selenium compounds did not demonstrate alteration on [(3)H]-glutamate uptake by synaptosomes, whereas lead acetate plus Ebselen showed an increase on [(3)H]-glutamate uptake. The results of the present study indicate that ALA-D inhibition antecedes the overproduction of reactive oxygen species, which is becoming well documented in the literature.     

Drug and food-deprivation modulation of activity in rats given chronic dietary lead: Significance of type of activity measure

In Experiment 1, rats were given a 1% lead acetate diet from Day 100 of life to the termination of the experiment. After 82 days of lead feeding behavioral tests were started. Lead exposure increased wheel-turning hyperactivity produced by food deprivation and phenylethylamine injection. Lead produced no activity change in the unchallenged condition. In the open field, lead-exposed rats were less responsive to the stimulating action of PEA and amphetamine and to the sedating action of pentobarbital. In Experiment 2, the interaction of lead with food deprivation or PEA on wheel-turning was replicated in naive animals given only a 32-day exposure. Chemical analysis was made of tissues. Ingested lead entered the brain. Regional steady-state levels of brain norepinephrine, dopamine and serotonin were not altered by lead treatment when measured following four days of starvation at a time when lead-induced behavioral change was distinct. It was concluded that pharmacological challenges on activity may be sensitive indicators of lead exposure, but the type of activity measure is critical.     

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.     

Effect of lead toxicity on coenzyme Q levels in rat tissues

Lead is a persistent and common environmental contaminant, which chiefly plays a significant role in modern industry. Coenzyme Q acts as electron and proton carrier in mitochondria and functions as an antioxidant in its reduced form (ubiquinol). To investigate the hazardous effects of lead on the coenzyme Q level, rats were injected i.p. with lead acetate (5 mg/kg b.wt. daily for 6 weeks). Our results showed that the levels of both oxidized (ubiquinone) and reduced (ubiquinol) forms of coenzyme Q₉ and Q₁₀ in serum, brain, liver and kidney of lead-treated rats are quite different depending on the organ tissue type.     

Lead-induced alteration of apoptotic proteins in different regions of adult rat brain

In our earlier investigations, we have demonstrated the alteration of antioxidant enzymes in adult rat brain exposed to lead. This study was carried out to investigate the effect of lead on inducing apoptosis by choosing poly (ADP-ribose) polymerase (PARP), bcl-2 and caspase-3 expression as marker proteins in the cerebellum, the hippocampus, the brain stem and the frontal cortex. Adult male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks and parallel controls were maintained on sodium acetate. Both control and exposed rats were sacrificed at intervals of 4 and 8 weeks, brains were isolated and different regions namely the cerebellum, the hippocampus, the frontal cortex and the brain stem were separated and processed to investigate PARP, bcl-2 and caspase-3 expression using western blotting. The results suggest that lead induces region-specific response of expression in apoptotic proteins of rat brain showing more effect in hippocampus and cerebellum and less effect in frontal cortex and brain stem and it is tissue specific. However, results appear to conclude that PARP induced expression in hippocampus and cerebellum was more followed by mitochondrial and cytosolic damage.     

Antioxidant effects of alpha tocopherol, ascorbic acid and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats

Lead exposure related oxidative stress has been incriminated, at least in part, to its toxic effects in different organs. The present investigation was carried out to study the ameliorative effects of antioxidant (ascorbic acid, alpha tocopherol or L-methionine) alone and antioxidant (alpha tocopherol) plus a conventional chelator (CaNa2 EDTA) on some of the parameters indicative of oxidative stress in the liver, kidney and brain in lead-exposed rats. Rats were given 0 (n=6, healthy controls) or 1 mg of Pb(2+)/kg b.w (n=30) as lead acetate solution in sterile normal saline ip for a period of 4 weeks. The ip injections were then withdrawn and lead exposed rats were randomly divided into five equal groups. Six lead-exposed rats were given no treatment during the 5th week (Pb group) to serve as positive controls. The rest four groups received either ascorbic acid, alpha tocopherol or L-methionine in the 5th week at the daily dose of 100 mg/kg b.w orally or alpha tocopherol as above plus CaNa2 EDTA at the rate of 110 mg/kg b.w twice a day ip for a period of 4 days. All the animals were sacrificed 1 day after the end of the experiment, and the liver, kidney and brain were quickly excised for the estimation of lead burden and alteration in the oxidative indices. Lead exposure for a period of 4 weeks followed by a period of 1 week to recover, resulted in significantly (P<0.05) higher accumulation of lead, associated with significant (P<0.05) increases in lipid peroxide level in the liver and brain, and non-protein bound thiol contents in the brain. Changes in the superoxide dismutase and catalase activities in lead-exposed rats did not reach statistical (P<0.05) significance. Treatment with antioxidants alone resulted in reversal of oxidative stress without significant decline in tissue lead burden. Tissue specific changes, following lead exposure and responses to the treatment with different antioxidants were recorded in the parameters of oxidative damage viz. lipid peroxide level, antioxidant enzymes and thiol contents.     

Morphometric and enzymatic effects of neonatal lead exposure in the rat brain

Lead acetate (7.5 mg/kg ip) was administered to rat pups from birth to 10 days of age. This dose did not impair weight gain or produce overt signs of lead toxicity. The animals were sacrificed at 10, 15, 20, or 30 days of age for enzymatic analysis or morphometric assessment. Thickness of the pyramidal cell layer of the hippocampal formation and of the granular cell layer of the dentate gyrus was measured. The activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was determined in homogenates from separate brain regions. Significant (p < 0.05) reductions of AChE activity were produced at 10 days in the hippocampus (40%) and medulla oblongata (17%). Although cerebral AChE was reduced by 17%, the reduction of hippocampal AChE (32%) was not significant nor were decreases in AChE observed in either the cerebellum, midbrain, corpus striatum, or medulla oblongata of 20-day-old lead-treated rats. No inhibition of BuChE activity was observed at 10 days. However, BuChE of the midbrain, hippocampus, and cerebrum of 15-day-old animals was decreased by 32, 37, and 12%, respectively. Similrly, BuChE activity of homogenates from the cerebrum, hippocampus, and midbrain of 20-day-old lead-treated rats was reduced by 35, 35, and 37%, respectively. No significant decreases in AChE or BuChE activity were produced in brain homogenates from 30-day-old animals. Measurements of hippocampal cell layer thickness and distance from the hippocampus to the cerebral cortex indicated that lead administration produced 10–15% reductions in both parameters. The results suggest that lead exposure may produce a reversible impairment of AChE and BuChE in specific brain regions of the developing rat brain. However, morphological effects of lead exposure may persist after the effects on BuChE and AChE activities are no longer discernible.     

Immunomodulatory and antioxidant protective effect of Sarcocornia perennis L. (swampfire) in lead intoxicated rat

Lead (Pb) is a very toxic metal present in the environment, causing disturbances of several functions. Preventive or curative effects of halophytic plants against these disorders may be a promising and safe therapeutic strategy. Thus, this study was designed to evaluate in vivo immunomodulatory and antioxidant effects of Sarcocornia perennis extract (Sp) against lead toxicity in rats. Groups of six animals each were treated with plant extract (via food), 6?g/L lead acetate (via drinking water) or a combination of both. At the end of the three-week period, rat exposure to lead caused reduction of liver weight but an increase of that of kidney. Moreover, lead intoxication-induced oxidative stress manifested by significant increases of inflammatory cytokines (except IL-10) and lipid peroxidation (TBARS), compared with the control group. Meanwhile, interleukin-10 (IL-10) and glutathione levels (GSH), as well as antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were decreased. Considering liver and renal markers, lead treatment induced a significant increase in the activities of aminotransferases (AST, ALT), and in the levels of urea, creatinine and phosphorous, whereas total plasma protein, albumin and calcium levels were significantly decreased. S. perennis extract alone did not induce any significant changes in hepatic or renal markers, whereas the antioxidant markers were significantly increased. S. perennis supplementation significantly reduced the lead-induced elevation of serum IL-1ß, IL-6, TNF-α, IFN-γ and TBARS but increased the IL-10 and antioxidant enzyme activities. Overall, plant components ameliorated hepatorenal damages caused by lead.     

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.     

Protective effect of Etlingera elatior (torch ginger) extract on lead acetate--induced hepatotoxicity in rats

Lead is known to disrupt the biological systems by altering the molecular interactions, cell signaling, and cellular function. Exposure to even low levels of lead may have potential hazardous effects on brain, liver, kidneys and testes. The efficacy of Etlingera elatior (torch ginger) to protect hepatotoxicity induced by lead acetate was evaluated experimentally in male Sprague - Dawley rats. Rats were exposed to lead acetate in drinking water (500 ppm) for 21 days and the effects of concurrent treatment with extract of E. elatior on hepatic lipid hydroperoxides (LPO), protein carbonyl content (PCC), total antioxidants (TA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione S- Transferase (GST) levels and histopathological changes in liver were evaluated. There was a significant decrease in TA and other antioxidant enzymes (p < 0.05) and increase in LPO and PCC (p < 0.05) with lead acetate ingestion. Concurrent treatment with E. elatior extract significantly reduced the LPO and PCC (p < 0.05) in serum and increased the antioxidant enzyme levels (p < 0.05) in the liver. Significant histopathological changes were seen in hepatic tissue with chronic lead ingestion. Treatment with E. elatior significantly reduced these lead-induced changes in hepatic architecture. E. elatior has also reduced the blood lead levels (BLL). Thus, there has been extensive biochemical and structural alterations indicative of liver toxicity with exposure to lead and E. elatior treatment significantly reduced these oxidative damage. Our results suggest that E. elatior has a powerful antioxidant effect against lead-induced hepatotoxicity.     

慢性铅暴露对大鼠脑组织 XRCC1 mRNA 表达的影响及其与氧化应激的关系

目的 观察饮水铅暴露对大鼠大脑皮质、 小脑、 海马组织中 X 线交错互补修复基因 1（XRCC1）mRNA 表达的影响及其与氧化应激的关系。方法 40 只 SD 大鼠根据体质量按随机区组法分对照组和 4 个铅暴露组： 最低剂量组、 低剂量组、 中剂量组、 高剂量组, 对照组自由饮用去离子水, 4 个铅暴露组分别饮用 100、 200、 400、 800 mg/L 的醋酸铅溶液, 连续染毒 60 d 后取大脑皮质、 小脑和海马。RT-PCR 技术检测脑组织 XRCC1 mRNA 的表达量, 并测定脑组织铅、 过氧化氢酶 （CAT）、 谷胱甘肽 （GSH） 和过氧化氢 （H2O2） 的含量。结果 与对照组比较, 铅暴露组大鼠大脑皮质、 小脑和海马中 XRCC1 mRNA 表达量、 脑铅的含量和 H2O2水平均升高(P＜0.05); 而 CAT、 GSH 含量基本低于对照组 （P < 0.05）; 相关性分析显示铅暴露组大鼠大脑皮质、 小脑和海马中 XRCC1 mRNA 表达量与脑组织铅含量呈正相关(r 分别为 0.608、 0.438、 0.470, P＜0.01), 与 CAT、 GSH 呈负相关 （r 分别为-0.343、 -0.465、 -0.423, -0.383、 -0.489、 -0.366, P＜0.05）, 与 H2O2 呈正相关(r 分别为 0.455、 0.517、 0.342, P＜0.05)。结论 铅可通过诱导细胞氧化应激而影响 XRCC1 mRNA 的表达。     

Developmental changes of the activity of monoamine oxidase in pre- and postnatally lead exposed rats

The effects of prenatal and postnatal lead exposure on monoamine oxidase (MAO) activity were investigated in rat brain. MAO activity was examined in 2, 4, 6, and 8 weeks old rat to investigate the effects of lead in the different stages of rat brain development. Prenatal lead exposure was achieved by providing mother rats with drinking water containing either low (0.05%) or high (0.2%) concentration of lead acetate from gestation to birth. Postnatal lead treatment was performed through drinking water to mothers and pups from birth to the day of experiment. MAO activity was gradually increased with the development in all the brain regions examined, i.e. telencephalon, diencephalons, midbrain, pons/medulla, and cerebellum. Lead exposure increased MAO activity in most of the brain regions especially at early developmental stages (2 weeks of age) and the toxicity was gradually decreased with the development of rats. High concentration of lead showed greater effects on MAO activity compared to low concentration. Postnatal lead exposure showed stronger effects on MAO activity compared to prenatal lead exposure demonstrating the importance of preventing lead exposure to lactating mother. The increased MAO activity by lead intoxication may contribute to the neurobehavioral changes such as cognitive and attention deficit as well as hyperactivity, which is commonly observed both in lead intoxication and perturbed monoaminergic neurotransmission.     

The influence of dietary phosphate on the toxicity of orally ingested lead in rats

The influence of elevated dietary phosphate on the toxicity of orally ingested lead was investigated in male weanling Wistar rats. Two groups of 20 rats were fed diets containing either adequate (0.5%) or high (1.2%) levels of phosphorus (as phosphates). Half of the rats on each level of phosphorus were given 20 μg lead (as lead acetate)/g dry diet. After 8 wk, biochemical tests for lead toxicity were carried out and tissue-lead levels were measured. All of the given lead-supplemented diets had higher concentrations of lead in bone, brain, kidney and liver than those given diets without added lead but the increase was significantly greater in all tissues in the group given the 1.2% phosphorus diet. Lead supplementation increased the levels of free erythrocyte protoporphyrin and decreased the activity of δ-aminolaevulinic acid dehydratase. The lead-induced increase in the level of free erythrocyte protoporphyrin was no greater in the high-phosphate group than in the low-phosphate group but the decrease in δ-aminolaevulinic acid dehydratase activity was significantly larger in the high-phosphate group. This work demonstrates that excess dietary phosphate significantly increases lead toxicity and indicates the need for continued research on the interaction between dietary factors and lead toxicity.     

The protective effect of rutin against renal toxicity induced by lead acetate

Flavonoids are known to have powerful antioxidant activity that could play a protective role in oxidative stress-mediated diseases. Rutin (RT) is a flavonol glycoside composed of the flavonol quercetin and disaccharide rutinose. The protective effect of RT against nephrotoxicity induced by lead acetate was evaluated. Male albino rats of Wistar strain were used in this study. Animals were given lead acetate after a week of pretreatment with RT (50?mg/animal/day). Lead acetate exposure resulted in an increase in the uric acid, creatinine (CRN) and blood urea nitrogen (BUN) levels and a decrease in glutathione, superoxide dismutase, catalase and glutathione peroxidase (GPx) activities. Lead acetate treatment decreased GSH levels by 2-fold and the activities of GSH metabolizing enzymes decreased to a range of 2–2.5-fold in renal tissue (p?<?0.05). These changes were reversed significantly in animals receiving pretreatment of RT. Treatment of rats with RT prior to the treatment with lead resulted in the recovery of reduced levels of GSH, GSH-metabolizing enzymes to almost 85–90%. RT has a beneficial impact on lead-induced toxicity due to its scavenging and antioxidant effect in rats.     

Continuous exercise training and curcumin attenuate changes in brain-derived neurotrophic factor and oxidative stress induced by lead acetate in the hippocampus of male rats

Context: For many years it has been known that lead is life-threatening, not only as an air pollutant but also because of it has been associated with several conditions including neurodegenerative disease. Curcumin (the principal curcuminoid found in turmeric) has demonstrated potent antioxidant properties.

Objective: We investigated neuroprotective effects of endurance exercise and/or curcumin on lead acetate-induced neurotoxicity in the rat hippocampus.

Materials and methods: Forty male Wistar rats were randomly divided into five groups: 1) lead acetate, 2) curcumin, 3) training, 4) training + curcumin, and 5) control. The rats in the training groups performed treadmill running five times a week for 8 weeks (15–22 m/min, 25–64?min). All groups except control received lead acetate (20?mg/kg), whereas the control group received curcumin solution (ethyl oleate). In addition, the curcumin and training + curcumin groups received curcumin solution (30?mg/kg) intraperioneally.

Results: Lead acetate resulted in a significantly increase in the malondialdehyde (MDA) in plasma (72%), but not significant in hippocampus (59%). In addition, it led to significantly decreased brain-derived neurotrophic factor in hippocampus (17%) and total antioxidant capacity (27%), as compared to control group. Treadmill running, curcumin supplementation or both resulted in a significant decrease in hippocampus MDA (17, 20, 31%, respectively) and plasma MDA (60, 22, 71%) and also, significantly increased brain-derived neurotrophic factor (76, 45, 94%) and total antioxidant capacity (47.13, 47.11, 61%) levels, as compared to lead acetate group.

Discussion and Conclusion: These results provide a rationale for an inhibitory role of curcumin and regular exercise in the attenuation of lead-induced neurotoxicity.     

饮水铅暴露对大鼠脑组织 APE1 表达的影响及与氧化应激的关系研究

目的 探讨饮水铅暴露对大鼠大脑皮质、 小脑、 海马组织中脱嘌呤脱嘧啶核酸内切酶 1（APE1）表达的影响及其与氧化应激的关系。方法 40 只刚断乳雄性 SD 大鼠按体质量随机区组法均分为 5 组, 对照组自由饮用去离子水, 4 个铅暴露组分别饮用 100、 200、 400 和 800 mg/L 醋酸铅溶液, 连续染毒 60 d 后, 取大脑皮质、 小脑和海马组织, 测定各组的超氧化物歧化酶 （SOD） 活力、 过氧化氢 （H2O2） 水平和丙二醛 （MDA） 含量, 蛋白印迹法检测 APE1 蛋白在各组织中的表达。结果 铅暴露后, 大脑皮质、 小脑、 海马中 APE1 蛋白表达水平均低于对照组, 且随染铅剂量的升高呈逐渐下降趋势（P＜0.05）; 随着染铅剂量的升高, 大脑皮质、 小脑和海马中的 SOD 活力基本呈下降趋势; 而 H2O2及 MDA 含量随染铅剂量的升高基本呈逐渐升高趋势, 大脑皮质、 小脑和海马组织的 APE1 蛋白表达水平与其 SOD 活力呈正相关（r 分别为 0.619、 0.380、 0.375, P < 0.05） ,而与 H2O2水平和 MDA 含量呈负相关（r 分别为-0.472、 -0.535、 -0.436, -0.514、 -0.486、 -0.316, P < 0.05）。结论 饮水铅暴露可导致大鼠脑组织 APE1 蛋白表达水平改变,且此种改变与铅所致的氧化应激有关。