Lead-treated Rats Research Articles

Alhagi maurorum Ethanolic Extract Rescues Hepato-Neurotoxicity and Neurobehavioral Alterations Induced by Lead in Rats via Abrogating Oxidative Stress and the Caspase-3-Dependent Apoptotic Pathway.

This work investigated the probable protective effect of an Alhagi maurorum ethanolic extract on the hepatotoxicity and neurotoxicity accompanied by neurobehavioral deficits caused by lead in rats. Rats in four groups were orally administered distilled water, ethanolic extract of A. maurorum (300 mg/kg BW daily), lead (100 mg/kg BW daily for 3 months), and lead + A. maurorum extract. The results demonstrated that lead exposure resulted in elevated locomotor activities and sensorimotor deficits associated with a decrease in brain dopamine levels. Moreover, lead exposure significantly increased liver function markers. In addition, the lead-treated rats exhibited extensive liver and brain histological changes and apoptosis. The lead treatment also triggered oxidative stress, as demonstrated by the increase in malondialdehyde (MDA) concentrations with a remarkable reduction in the activities of antioxidant enzymes, reduced glutathione (GSH) levels, and transcriptional mRNA levels of antioxidant genes in the liver and brain. Nevertheless, co-treatment with the A. maurorum extract significantly ameliorated the lead-induced toxic effects. These findings indicate that the A. maurorum extract has the ability to protect hepatic and brain tissues against lead exposure in rats through the attenuation of apoptosis and oxidative stress.

Neurobehavioural and Histological Alterations in Lead Acetate-Exposed Rats Pretreated with Aqueous Leaf Extract of Vernonia amygdalina

Lead is a systemic toxicant that affects virtually every organ system, primarily the central nervous system, through an increase in the production of reactive oxygen species (ROS). This increase in ROS overwhelms the natural antioxidant system of the body leading to oxidative stress. Some plants such as Vernonia amygdalina have been reported to possess antioxidant activity which counteracts the damage induced by free radicals. Accordingly, this study was designed to investigate the possible protective activity of aqueous Vernonia amygdalina leaf extract against lead-induced neurotoxicity in adult Wistar rats. Thirty Wistar rats were randomised into six groups (A-F) consisting of five rats each for a study period of 28 days. Group A served as the control group, Group B was administered with 100mg/kg body weight of lead only, Groups C and D were pretreated with 200mg/kg and 400mg/kg bodyweight of aqueous Vernonia amygdalina leaf extract and 100mg/kg body weight of lead respectively. Groups E and F were administered with 200mg/kg and 400mg/kg body weight of aqueous Vernonia amygdalina leaf extract only. The Open field and Novel Object Recognition tests were assessed and thereafter, the cerebellum, cerebrum and hippocampus were harvested for histological examination. Results showed a significant decrease in the body and brain weights, ambulation, rearing and discrimination index as well as a conversely significant increase in grooming and immobility in lead-treated rats. Histological examination of lead-alone treated groups showed loss of some Purkinje cells in the cerebellum, degenerating pyramidal cells in the cerebrum and altered morphology with pyknotic nuclei in the hippocampus. Pretreatment of rats with Vernonia amygdalinaattenuated lead-induced alterations to body and brain weights, neurobehavioural activities and tissue histomorphology, thus indicating a potent protective activity. These findings provide the first research evidence that Vernonia amygdalina protects against lead-induced neurotoxicity in Wistar rats.

Subchronic Oral Administration of Lead Exacerbate Liver and Kidney Toxicity in Male Wistar Rats

Lead is an environmental and occupational toxicant. Compelling experimental data from previous studies have shown that following lead exposure, highest concentration of the absorbed lead is stored in the liver and the kidney, and this is expected to have severe consequences on the two organs. In this study, we investigated the effects of lead on the hepatic and renal structure and functions. Rats (n=24) were grouped into four of six animals each. Group 1(control) received drinking water only. Groups 2, 3 and 4 were orally exposed to 50, 100 and 150 mg/kg body weight of lead respectively for 12 weeks, after which, blood, liver, and kidney were collected from the animals for biochemical and histological studies. One-way analysis of variance followed by Tukey’s test was used to analyze the results with (p <0.05) considered significant. Lead exposure caused a general decline in the percentage body weight gain and percentage relative liver weight. Physical trauma was also observed in the lead-treated rats. The lead exposure also significantly (p <0.05) enhanced the plasma activities of aspartate and alanine aminotransferases, gamma-glutamyl transferase, lactate dehydrogenase, and alkaline phosphatase. Furthermore, a significant increase (p <0.05) was observed in the concentration of creatinine and urea in the plasma of the lead-exposed animals. The histological study also revealed several histological alterations in the liver and kidney of lead-exposed animals relative to the control animals. These findings indicated that exposure to lead may have adverse effects on the structure and function of both the liver and the kidney.

The Effect of The Sorrel Extract on Hepatic Enzymes of Lead-Treated Rats

The Effect of The Sorrel Extract on Hepatic Enzymes of Lead-Treated Rats

Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

Lead (Pb) exposure causes hazardous effects as hypertension and other cardiovascular diseases. We evaluated whether chronic Pb exposure alters the peripheral vascular resistance measuring the vascular reactivity of mesenteric resistance arteries in rats to identify the underlying mechanisms that are associated to the development of Pb-induced hypertension. Mesenteric resistance arteries from lead-treated and untreated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) were used. Contractile responses to phenylephrine increased, while acetylcholine and sodium nitroprusside-induced relaxation was not affected by lead treatment. Endothelium removal and inhibition of NO synthase by L-NAME similarly enhanced the response to phenylephrine in untreated and lead-treated rats. The antioxidants apocynin and superoxide dismutase (SOD) did not affect vasoconstriction in either group. The vascular expression of cyclooxygenase-2 (COX-2) protein increased after lead exposure. The respective non-specific or specific COX-2 inhibitors indomethacin and NS398 reduced more strongly the response to phenylephrine in treated rats. Antagonists of EP1 (SC19220), TP (SQ29548), IP (CAY10441) and angiotensin II type 1 (losartan) receptors reduced vasoconstriction only in treated rats. These conclusions present further evidence that lead, even in small concentration, produces cardiovascular hazards being an environmental contaminant that account for lead-induced hypertension.

Exposure to Aqueous-Alcoholic Extract of Parsley Leaves (Petroselinum crispum) in Lead-Treated Rats Alleviate Liver Damage

Exposure to Aqueous-Alcoholic Extract of Parsley Leaves (Petroselinum crispum) in Lead-Treated Rats Alleviate Liver Damage

Effect of intra-hippocampal lead injection on affective and cognitive disorders in male WISTAR rats: Possible involvement of oxidative stress

This paper is focused on affective and cognitive disorders induced by direct exposure to lead chloride (Pb) and the possible implication of oxidative stress in male WISTAR rats. Using stereotaxic surgery, a group of male wistar rats received an intracerebral injection of 3 μL of lead chloride (1 mg / L) into the right hippocampus or 3 μL of 0.9% Nacl for shame operated controls groups. After 4 days of rest, a series of benchmark neurobehavioral tests were made to evaluate affective and cognitive behaviors, such as open field test (OFT) and Elevated plus maze (EPM) for anxiety like behavior; Forced swim test (FST) for depressive like behavior; finally Y maze (Y-Maze) and Morris maze (MWM) tests for working memory, spatial learning and spatial memory. The data showed that Pb induces anxiogenic and depressogenic effects but does not induce a significant effect in memory. Then by measuring oxidative stress markers using the hippocampal assay of lead-treated rats, it’s appears that Pb can increase nitrogen monoxide, lipid peroxidation and reduces significantly the activity of superoxide dismutase. Therefore, our results showed that Pb is able to induce affective disorders and increase highly oxidative stress but has an insignificant effect on cognitive impairment.

Cichorium intybus L. extract ameliorates testicular oxidative stress induced by lead acetate in male rats.

ObjectiveOxidative stress has been suggested as a possible mechanism for the adverse effects of heavy metal toxicity on male reproduction. Cichorium intybus L. is used in Iranian folk medicine as a hepatoprotective agent as well as for its supposed fertility-enhancing properties. The present study was performed to investigate whether the ethanolic extract of C. intybus leaves could protect male rats against lead-induced testicular oxidative stress.MethodsIn this experimental study, adult Wistar rats were treated with 0.1% lead acetate in drinking water alone or with 50, 100, or 200 mg/ kg body weight of C. intybus extract via gavage once daily for 70 days. The weight of their reproductive organs, levels of serum hormones, histometric parameters of the seminiferous tubules, epidydimal sperm quality, and oxidative stress status were evaluated.ResultsThe testis weight, seminiferous tubule diameter, epididymal sperm count, serum testosterone level, and testicular levels of superoxide dismutase and glutathione peroxidase were significantly reduced (p<0.05) in the lead-treated rats. Moreover, significantly (p<0.05) higher levels of malondialdehyde were observed in the lead-exposed group compared to the control. However, the co-administration of C. intybus ethanolic extract in lead-treated rats was associated with a significant improvement in reproductive parameters.ConclusionWe conclude that C. intybus leaf extract has the potential to prevent lead-induced testicular toxicity and to suppress the adverse effects of lead on male reproductive health.

Increased endothelial nitric oxide production after low level lead exposure in rats involves activation of angiotensin II receptors and PI3K/Akt pathway

BackgroundLead induces endothelial dysfunction and hypertension in humans and animals. Seven-day exposure to a low dose in rats reduces vasocontractile responses and increases nitric oxide (NO) bioavailability. We hypothesized that this occurs by angiotensin II receptors (AT1/AT2) activation. Materials and ResultsWistar rats were exposed to lead acetate (1 st dose 4 μg/100 g, subsequent dose 0.05 μg/100 g/day i.m., 7 days) or saline (control group). Lead acetate exposure reduced the phenylephrine vascular response. Pre-incubations with NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) increased the contractile response in aortas from lead-treated rats. Pre-incubation with AT2 antagonist (PD123319) restored normal vascular contraction, and both PD123319 or AT1 antagonist (losartan) impeded the potentiated effects of L-NAME and wortmannin. Reinforcing those findings, increased NO bioavailability was blunted by AT1 and AT2 antagonists without summative effect when co-incubated. Finally, to test whether activation of AT1 could upregulate AT2 to increase NO bioavailability rats were simultaneously exposed to lead acetate and treated with losartan (15 mg/kg/day, orally given). Losartan prevented changes on vascular reactivity and endothelial modulation in lead-exposed group. Moreover, incubation with PD123319 had no more effects in aortic from losartan-treated rats. ConclusionOur results suggest that low-dose lead acetate exposure induces an increase of NO involving mainly AT2 receptor activation and the PI3K/Protein Kinase B (PI3K/Akt) pathway. Additionally, we suggest that AT1 activation plays a role in AT2 upregulation, probably as a protective mechanism. Altogether, these effects might contribute to preserving endothelial function against the harmful effects by lead in the vascular system.

Alleviation of Lead-Induced Immunotoxicity by Moringa oleifera in Albino Rats

The existing study was designed to evaluate the ameliorative influences of Moringa oleifera on several immune parameters in male rats subsequent to lead administration. Twenty eight adult male rats were randomly assigned equally into 4 groups; control group was given distilled water. Lead treated rats were administrated a dose of 44 mg of lead acetate/kg BW. Moringa group was treated with 50 mg/ kg BW of Moringa oleifera leaf extract. Lead and moringa treated group was given a dose of 44 mg/kg of lead acetate and 50 mg/ kg of moringa extract. Treatments were given orally by gavage tube for one month. By the termination of the experimental period, rats were immolated; spleen and thymus weights were recorded in addition to the collection of blood and tissue samples. Tumor necrosis factor alpha (TNF-α), interferon gamma (IF-γ), interlukin-2 (IL-2) and total antioxidant capacity (TAC) were assayed in serum. Complete blood picture was evaluated for rats. Body weight gain was reduced significantly (P<0.05) in lead and moringa treated rats in comparison to control. A significant (P<0.05) increase in spleen weights was observed in lead and moringa co-administered group compared to moringa treated group. Lead administration produced higher (P<0.001) levels of TNF-α, IL-2 and IF-γ compared to that in other groups. In contrary, the level of TAC was significantly (P<0.001) reduced in lead treated rats. A significant (P<0.01) reduction in RBCs and low level of hemoglobin (P=0.07) were observed in lead-treated rats. Spleen of rats receiving lead showed widespread hyperplasia of lymphoid follicles in white pulp and hemosiderin pigment in red pulp. Thymus of rats receiving lead showed marked proliferation in the cortical region. Spleen and thymus of rats receiving lead showed a higher (P<0.01) immune reactivity for NF-κB and CD8+ parallel to that in other groups. In conclusion, the administration of Moringa oleifera extract ameliorates the immunotoxicity induced by lead exposure in rats.

Sodium Nitrite Prevents both Reductions in Circulating Nitric Oxide and Hypertension in 7-Day Lead-Treated Rats.

Hypotensive effects of oral sodium nitrite have been reported as alternative sources of nitric oxide (NO) formation in animals and human beings. Reductions in NO bioavailability were observed in lead-induced hypertension. However, no previous study has examined whether a single daily dose of sodium nitrite prevents the reductions in the NO bioavailability in lead-induced hypertension. Then, we expanded previous reports and evaluated the effects of sodium nitrite in 7-day lead-treated rats. Wistar rats were divided into four experimental groups: Pb+sodium nitrite group received intraperitoneally (i.p.) 1st dose 8 µg/100 g of lead acetate and a subsequent dose of 0.1 µg/100 g, and daily treatment with sodium nitrite (45 mg/kg/day) or water (Pb group) by gavage for 7 days; Sodium nitrite group received i.p. 1st dose 8 µg/100 g of sodium acetate and a subsequent dose of 0.1 µg/100 g, and daily treatment with sodium nitrite (45 mg/kg/day) or water (saline group) by gavage for 7 days. Similar and higher whole-blood lead levels (11.5 ± 1.2 and 13.2 ± 0.7 µg/dL) were found in lead-exposed rats treated with either water or sodium nitrite (Pb or Pb+sodium nitrite, respectively; both p < 0.05 versus control groups). We found lower NO markers such as plasma nitrite and nitrite + nitrate (NOx) levels (both p < 0.05 versus controls) in lead-exposed rats compared with normotensive (sodium acetate)-treated controls (Pb group versus saline group; p < 0.05). Lead induced increases in systolic blood pressure (from 130 ± 2 to 164 ± 6 mmHg in Pb group; p < 0.05); however, both lead-induced decreases in NO markers and hypertension (Pb+sodium nitrite group versus Pb group; both p < 0.05) were prevented by a single daily dose of sodium nitrite. In conclusion, these findings are consistent with the idea that impaired NO bioavailability contributes to the maintenance of elevated blood pressure in lead-induced hypertension. Additionally, our results show that sodium nitrite exerts antihypertensive effects in lead-induced hypertension and provide evidence that sodium nitrite prevents the impairment of NO, thus, reaffirming the relevance of nitrite as alternative source of recycling back to NO.

Chronic lead exposure decreases the vascular reactivity of rat aortas: the role of hydrogen peroxide.

We investigated whether exposure to small concentrations of lead alters blood pressure and vascular reactivity. Male Wistar rats were sorted randomly into the following two groups: control (Ct) and treatment with 100 ppm of lead (Pb), which was added to drinking water, for 30 days. Systolic blood pressure (BP) was measured weekly. Following treatment, aortic ring vascular reactivity was assessed. Tissue samples were properly stored for further biochemical investigation. The lead concentration in the blood reached approximately 8 μg/dL. Treatment increased blood pressure and decreased the contractile responses of the aortic rings to phenylephrine (1 nM–100 mM). Following N-nitro-L arginine methyl ester (L-NAME) administration, contractile responses increased in both groups but did not differ significantly between them. Lead effects on Rmax were decreased compared to control subjects following superoxide dismutase (SOD) administration. Catalase, diethyldithiocarbamic acid (DETCA), and apocynin increased the vasoconstrictor response induced by phenylephrine in the aortas of lead-treated rats but did not increase the vasoconstrictor response in the aortas of untreated rats. Tetraethylammonium (TEA) potentiated the vasoconstrictor response induced by phenylephrine in aortic segments in both groups, but these effects were greater in lead-treated rats. The co-incubation of TEA and catalase abolished the vasodilatory effect noted in the lead group. The present study is the first to demonstrate that blood lead concentrations well below the values established by international legislation increased blood pressure and decreased phenylephrine-induced vascular reactivity. The latter effect was associated with oxidative stress, specifically oxidative stress induced via increases in hydrogen peroxide levels and the subsequent effects of hydrogen peroxide on potassium channels.

MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100g; subsequent doses: 0.125μg/100g, intramuscular, 30days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20μg/dL) were used. Lead blood levels of treated rats attained 21.7±2.38μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension.

Proanthocyanidins improves lead-induced cognitive impairments by blocking endoplasmic reticulum stress and nuclear factor-κB-mediated inflammatory pathways in rats

Proanthocyanidins (PCs), a class of naturally occurring flavonoids, had been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor and anti-inflammatory. In this study, we examined the protective effect of PCs against lead-induced inflammatory response in the rat brain and explored the potential mechanism of its action. The results showed that PCs administration significantly improved behavioral performance of lead-exposed rats. One of the potential mechanisms was that PCs decreased reactive oxygen species production and increased the total antioxidant capacity in the brains of lead-exposed rats. Furthermore, the results also showed that PCs significantly decreased the levels of tumor necrosis factor-α, interleukin 1β and cyclooxygenase-2 in the brains of lead-exposed rats. Moreover, PCs significantly decreased the levels of beta amyloid and phosphorylated tau in the brains of lead-treated rats, which in turn inhibited endoplasmic reticulum (ER) stress. PCs also decreased the phosphorylation of protein kinase RNA-like ER kinase, eukaryotic translation initiation factor-2, inositol-requiring protein-1, c-Jun N-terminal kinase, p38 and inhibited nuclear factor-κB nuclear translocation in the brains of lead-exposed rats. In conclusion, these results suggested that PCs could improve cognitive impairments by inhibiting brain oxidative stress and inflammatory response.

Protective effects ofFumaria parvifloraL. on lead-induced testicular toxicity in male rats

In recent years, the clinical importance of herbal drugs has received considerable attention in reducing free radical-induced tissue injury. Oxidative stress has been proposed as a possible mechanism involved in lead toxicity that causes reproductive system failure in both human and animals. Fumaria parviflora L., a traditional herb, has been used to cure various ailments in Persian folk medicine. This study was carried out to investigate whether ethanolic extract of F.parviflora leaves could protect the male rats against lead-induced testicular oxidative stress. Adult Wistar rats were treated with 0.1% lead acetate in drinking water with or without 200mgkgday(-1) F.parviflora extract via gavage for 70days. Lead acetate treatment resulted in significant reduction in testis weight, seminiferous tubules diameter, epididymal sperm count, serum testosterone level, testicular content of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Moreover, significant elevation was observed in content of malondialdehyde (MDA) in lead-treated rats. However, co-administration of F.parviflora extract showed a significant increase in selected reproductive parameters in lead-treated rats. The results indicated that ethanolic extract of F.parviflora leaves has a potential to restore the suppressed reproduction associated with lead exposure and prevented lead-induced testicular toxicity in male Wistar rats.

Ameliorative effect of vitamin C on the haematological changes induced by exposure of chlorpyriphos and lead acetate in Wistar rats

The present study was designed to evaluate the effects of chlorpyriphos, lead acetate and vitamin C alone and in combinations, on various haematological parameters in Wistar rats. Rats of 150–200 g body weight were divided into eight groups of six animals each and were subjected to various daily oral treatment regimes for 98 days. Group C served as control receiving only corn oil, group CP received chlorpyriphos at 5.5 mg/kg in corn oil and group L received lead acetate at100 ppm in water, whereas animals in group CP + L received a combination of chlorpyriphos at 5.5 mg/kg in corn oil and lead acetate at 100 ppm in water. Group VC received vitamin C at 100 mg/kg in water; group CP + VC received a combination of chlorpyriphos at 5.5 mg/kg and vitamin C at 100 mg/kg; group L + VC received lead acetate at 100 ppm in water and vitamin C at 100 mg/kg and group CP + L + VC received chlorpyriphos at 5.5 mg/kg, lead acetate at 100 ppm in water and vitamin C at 100 mg/kg. Blood samples were collected on days 0, 30, 60 and 98 post exposure and analysed for packed cell volume (PCV), total erythrocyte count (TEC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total leucocyte count (TLC) and differential leucocyte count. A significant decrease in TEC, PCV and Hb and a significant increase in ESR values were observed. However, lead acetate caused an increase in TLC while chlorpyriphos resulted in a decrease in TLC. Both of these toxicants potentiated toxicity of each other. The study demonstrated that treatment of chlorpyriphos- and lead-treated rats with vitamin C significantly altered some of the important haematological parameters revealing the protective effect of this vitamin against haematological alterations induced by chlorpyriphos and lead.

The Effect of Vitamin C on the Erythrocyte Antioxidant Enzymes in Intoxicated-Lead Rat Offsprings

Lead exposure or lead poisoning is known to cause a large spectrum of physiological, biochemical, and behavioural disorders in animals. This study was aimed at assessing the effect of vitamin C on the erythrocyte superoxide dismutase, glutathione peroxidase and the glutathione reductase activities in intoxicated- lead rat offsprings. This study was performed on the pups from female Wistar albino rats. The rats were divided into 4 groups and the treatments were administered through drinking water. Group1 (control group) consumed distilled water. Group 2 (lead group) consumed a solution of lead acetate (300mg/L). Group3 (lead + vitamin C) consumed a solution of lead (300mg/L) which was supplemented with vitamin C (2g/L). Group4 (vitamin group) consumed a solution of vitamin C (2g/L). The enzyme activities were determined in all the 4 groups. The administration of lead showed a decrease in the enzyme activities. The superoxide dismutase activity was increased after the administration of lead in combination with vitamin C. The lead treated rats showed significantly lower body weights at birth and at weaning. The vitamin C treatment showed a significant increase in the body weight. The haemoglobin levels were significantly decreased in the lead-treated rats. The addition of vitamin C to the lead treatment and vitamin C alone could elevate the haemoglobin levels significantly. The results of this study showed that lead alterates the erythrocyte antioxidant enzyme activities. There was an increase in the superoxide dismutase activity following the treatment with vitamin C. This study suggests that the treatment with vitamin C during lactation has a therapeutic effect in the treatment of lead intoxication. The administration of vitamin C prevents haemoglobin reduction in the erythrocytes.

Activation of K+ channels and Na+/K+ ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats

Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K+ channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K+ channels and Na+/K+-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4μg/100g, subsequent doses 0.05μg/100g, im, 7days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O2− production, and apocynin (0.3μM), superoxide dismutase (150U/mL) and catalase (1000U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K+-induced relaxation curves. Ouabain (100μM) plus L-NAME (100μM), aminoguanidine (50μM) or tetraethylammonium (TEA, 2mM) reduced the K+-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60mM/L) or preincubated with TEA (2mM), 4-aminopyridine (4-AP, 5mM), iberiotoxin (IbTX, 30nM), apamin (0.5μM) or charybdotoxin (0.1μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K+ channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress.

Effects of chronic lead intoxication on rat serotoninergic system and anxiety behavior

Chronic lead exposure has been shown to produce behavioral disturbances in human and animal models. These disturbances are associated with alterations in monoaminergic neurotransmission in the central nervous system (CNS), some of which have been attributed to serotonin (5-HT). This study was undertaken to investigate the chronic effects of lead exposure on the serotoninergic system in the dorsal raphe nucleus (DRN) and the consequences of its toxicity on rat behavior. Adult male Wistar rats were chronically exposed for 3 months to 0.5% lead acetate in drinking water. The serotoninergic system was evaluated using immunohistochemistry and the anxiety behavior was assessed by the light/dark box test. The results show that chronic lead exposure induces a significant increase of blood and brain lead levels in treated rats compared with controls. The density of the immunoreactive serotoninergic cell bodies was significantly higher in treated rats in all parts of the DRN. Assessment of animal behavior using the light/dark box test showed that lead-treated rats spent significantly more time in the light chamber compared with controls ( P = 0.001). These findings suggest that lead exposure may possibly induce increased anxiety as a consequence of changes in neuronal 5-HT content in the DRN.

The effect of L-ascorbic acid and/or tocopherol supplementation on electrophysiological parameters of the colon of rats chronically exposed to lead

SummaryBackgroundThe aim of this study was to assess the effect of diet supplementation with L-ascorbic acid (500 mg/L), tocopherol (3 mg/kg b.w.), and/or a water soluble analog of tocopherol (Trolox) (48 mg/L) on ion transport in the colon of rats subjected to a chronic exposure (9 months) to 0.1% lead acetate in drinking water.Material/MethodsThe electrophysiological parameters of the colon wall were measured with Ussing methods. Lead content in the whole blood was analyzed by graphite furnace atomic absorption spectrometry (GFAAS) using Zeeman correction. L-ascorbic acid and tocopherol in plasma was measured by high performance liquid chromatography. Immunohistochemical reaction was carried out for visualization of occludin, the intracellular tight junction protein.ResultsWe showed a strong inhibitory effect of lead on the electrophysiological parameters, changes in intestinal permeability, disappearance of junctional occludin, decreased amount of mucus covering the colon surface, and the accumulation of PAS-positive substance in the apical region of the cytoplasm in the absorptive cells.ConclusionsSupplementation with tocopherol or Trolox did not exert a beneficial influence on the studied parameters. L-ascorbic acid positively influenced the examined electrophysiological parameters, as it cancelled the inhibitory influence of lead on ion transport in the rat colon. L-ascorbic acid also protected against tight junction disruption of epithelial cells in the colon of the lead-treated rats. A similar effect was observed in the group of rats receiving lead and supplemented with L-ascorbic acid plus Trolox.