Impact of Moringa oleifera leaf extract in reducing the effect of lead acetate toxicity in mice

This study aimed to assess the impact of Moringa oleifera (M. oleifera) leaf extract against the poisoning of lead acetate; therefore, sixty mice were allocated into 4 groups with 15 in each, as G1) blank control, G2) supplied with 300 mg/kg body weight (BWT). M. oleifera extract, G3) supplied with 60 mg/kg BWT of lead acetate [Pb(C₂H₃O₂)₂], and G4) supplied with extract of M. oleifera + lead acetate. The liver enzymes were elevated post-treatment with Pb(C₂H₃O₂)₂, which then lowered to almost the normal level when M. oleifera was supplied to mice previously treated with Pb(C₂H₃O₂)₂. The values in (G3) decreased when compared with G1 (92.33 ± 12.99, 21.67 ± 2.91 and 98.00 ± 13.20 U/L, respectively. Also, the cholesterol and low-density lipoprotein levels were elevated post-supplementation with M. oleifera and Pb(C₂H₃O₂)₂. Pb(C₂H₃O₂)₂ improves the lipid profile, whereas M. oleifera pretreatment reduced cholesterol (CHOL), high density low cholesterol (HDL-c), and low-density low cholesterol (LDL-c) levels in animals fed Pb(C₂H₃O₂)₂. Pb(C₂H₃O₂)₂ elevates the total protein but lowers the total bilirubin and triglycerides post M. oleifera treatment and Pb(C₂H₃O₂)₂ when contrasted with G1. The protective effect of M. oleifera was caused by the fact that it lowered triglycerides (TG) and total bilirubin (TBIL) and raised total protein (TP). After administration of Pb(C₂H₃O₂)₂, the histological examination revealed alterations in the hepatocytes and kidneys of G3. Also, the liver and kidney cells in mice supplied with M. oleifera after Pb(C₂H₃O₂)₂ poisoning recovered. In conclusion, Pb is toxic, and the usage of M. oleifera partially enhances the negative impacts induced by Pb(C₂H₃O₂)₂.     

Effects of lead administered during pregnancy to C57B1 mice]

Treatment of female mice with high doses of lead from different times of the gestation, induces abortion or retardation of growth of the embryos. When it is given from birth, it provokes important mortality in the youngs and a retardation of the postnatal growth. In most cases, lead administered from the first day of gestation delays slightly the development of the embryo and inhibits its implantation. It seems that a deficiency in the plasmatic progesterone levels is directly implied in this inhibition.     

Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice

Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in the liver and spleen manifested by hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen is represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system.     

alpha-Tocopherol modifies lead induced functional changes at murine neuromuscular junction

Lead impacts neuromuscular junction and might induce skeletal muscle weakness. Antioxidants may prevent toxic actions of lead on muscle. In this study, resting membrane potentials, endplate potentials, miniature endplate potentials (MEPPs) and isometric twitch tensions were recorded to investigate effects of alpha-tocopherol (Vitamin E) on lead induced changes at murine dorsiflexor muscle. Moreover, levels of endplate nicotinic receptors were measured by receptor autoradiography. Forty rats were divided into four groups (lead alone, alpha-tocopherol, lead plus alpha-tocopherol and saline). Lead (1 mg/kg, i.p.), was administered daily for 2 weeks and alpha-tocopherol (100 mg/kg, i.p.) was given daily for 3 weeks. Lead treatment significantly reduced twitch tension (from 4.4+/-0.4 to 2.2+/-0.3 g) and delayed half time of decay. MEPP frequencies and quantal content were also significantly reduced after lead treatment. Pretreatment with alpha-tocopherol reversed twitch tension reduction (4.1+/-0.3 g) and modified lead induced delay in half time of decay. Similarly, alpha-tocopherol modified the negative actions of lead exposure on MEPP frequencies and quantal content. Receptor autoradiographic studies revealed significant increase of nicotinic receptor levels at the endplate region of flexor muscle in lead treated mice. However, animals treated with lead plus alpha-tocopherol showed significantly decreased levels of nicotinic receptors. alpha-Tocopherol appears to protect against lead induced neuromuscular dysfunction. These effects of alpha-tocopherol are possibly mediated via a free radical mechanism or modification of calcium homeostasis.     

Daf-2 signaling modifies mutant SOD1 toxicity in C. elegans

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS.     

Reproductive and embryological toxicity of lead acetate in male mice and their offspring and mitigation effects of quercetin

Exposure to heavy metals not only impacts on fertility in males, it may also affect the offspring. The aim of the present study was to examine the toxic effects of lead acetate on fertility in male mice and their offspring, and the potential effect of quercetin on mitigating the likely effects. Experimental mice were randomly divided into three groups and administered with (i) distilled water (control); (ii) lead acetate (150 mg/kg BW/day); (iii) lead acetate (150 mg/kg BW/day) with quercetin (75 mg/kg BW/day). Lead acetate administration in male mice adversely affected their fertility through changes in sperm motility, viability, morphology, maturity, membrane integrity, and intracellular reactive oxygen species (P < 0.05). Similar findings were observed in the offspring of the lead-treated male mice. Early embryonic development and implantation rate were also adversely influenced in both the sires and offspring when male mice were treated with lead acetate (P < 0.05). The data demonstrated that down-regulation of Cks2 (CDC28 protein kinase regulatory subunit-2) in sperm had an association with early embryonic development in lead acetate treated group. In conclusion, lead acetate administration adversely impacted on the fertility of the male mice and their male offspring fertility; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on male mice and their offspring.     

Charcoal suspension for tumor labelling modifies macrophage activity in mice

We have previously developed a charcoal suspension for injection into human breast cancers in order to facilitate their location during surgery. We observed that charcoal particles were ingested by intra and peritumoral macrophages, some of which carried the particles at some distance from the injection site. We studied the influence of the formulation parameters of the charcoal suspension for intratumoral injection on in vitro and in vivo activation and in vivo mobilization of mouse peritoneal macrophages after intra-peritoneal injection of 2 mL of each preparation. The influence of the charcoal origin (peat vs wood), granulometry, suspension vehicle (water for parenteral injection, vs saline), concentration and excipients were studied. Micronized peat charcoal in water for injection at the highest studied concentration reduced macrophage activation in vitro and in vivo. However, macrophage mobilization was weaker than after thioglycolate injection and did not seem to be charcoal dose-dependent. The additives incorporated in the charcoal suspension led in vivo to increased peritoneal macrophage activation and mobilization (mannitol, and glucose), only increased activation (polysorbate 80 and pluronic F68) or mobilization (dextran 40, egg lecithin, and cabosil), or inhibited both activation and mobilization (cremophor EL).     

Antioxidant role of alpha-lipoic acid in lead toxicity.

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentration-dependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.     

Role of selenium against lead toxicity in male rats

Male albino rats were intramuscularly administered a single dose of lead acetate (100 μmol/kg b.wt). Another group of rats were injected with sodium selenite (10 μmol/kg b.wt) before lead intoxication. After 3 and 24 hours, lead treatment resulted in significant increases in acid and alkaline phosphatases, GOT and GPT, total proteins, and cholesterol in serum. The total triglycerides in serum was decreased after 24 hours of intoxication. Lead treatment also produced significant elevation of lipid peroxidation in liver and kidney. The antioxidant capacity of hepatic and renal cells in terms of the activities of superoxide dismutase, glutathione reductase, and glutathione content was diminished. It appears from these results that lead may exert its toxic effect via peroxidative damage to renal and hepatic cell membranes after 24 hours. Selenium administration prior to lead injection produced pronounced prophylactic action against lead effects, and it is observed that selenium enhances the endogenous antioxidant capacity of the cells by increasing the activities of the superoxide dismutase and glutathione reductase and the glutathione content. As a result, the lipid peroxidation was decreased in both liver and kidney. © 1998 John Wiley & Sons, Inc. J Biochem Mol Toxicol 12: 345–349, 1998     

Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice

We previously reported that ubiquitin-specific protease (USP) 2 in macrophages down-regulates genes associated with metabolic diseases, suggesting a putative anti-diabetic role for USP2 in macrophages. In this study, we evaluate this role at both cellular and individual levels. Isolated macrophages forcibly expressing Usp2a, a longer splicing variant of USP2, failed to modulate the insulin sensitivity of 3T3-L1 adipocytes. Similarly, macrophage-selective overexpression of Usp2a in mice (Usp2a transgenic mice) had a negligible effect on insulin sensitivity relative to wild type littermates following a three-month high-fat diet. However, Usp2a transgenic mice exhibited fewer M1 macrophages in their mesenteric adipose tissue. Following a six-month high-fat diet, Usp2a transgenic mice exhibited a retarded progression of insulin resistance in their skeletal muscle and liver, and an improvement in insulin sensitivity at an individual level. Although conditioned media from Usp2a-overexpressing macrophages did not directly affect the insulin sensitivity of C2C12 myotubes compared to media from control macrophages, they did increase the insulin sensitivity of C2C12 cells after subsequent conditioning with 3T3-L1 cells. These results indicate that macrophage USP2A hampers obesity-elicited insulin resistance via an adipocyte-dependent mechanism.     

Teratogen update: lead and pregnancy

This review focuses on the impacts of lead exposure on reproductive health and outcomes. High levels of paternal lead exposure (>40 microg/dl or >25 microg/dl for a period of years) appear to reduce fertility and to increase the risks of spontaneous abortion and reduced fetal growth (preterm delivery, low birth weight). Maternal blood lead levels of approximately 10 microg/dl have been linked to increased risks of pregnancy hypertension, spontaneous abortion, and reduced offspring neurobehavioral development. Somewhat higher maternal lead levels have been linked to reduced fetal growth. Some studies suggest a link between increased parental lead exposure and congenital malformations, although considerable uncertainty remains regarding the specific malformations and the dose-response relationships. Common methodological weaknesses of studies include potential exposure misclassifications due to the frequent unavailability of exposure biomarker measurements at biologically appropriate times and uncertainty regarding the best exposure biomarker(s) for the various outcomes. A special concern with regard to the pregnant woman is the possibility that a fetus might be exposed to lead mobilized from bone stores as a result of pregnancy-related metabolic changes, making fetal lead exposure the result of exposure to exogenous lead during pregnancy and exposure to endogenous lead accumulated by the woman prior to pregnancy. By reducing bone resorption, increased calcium intake during the second half of pregnancy might reduce the mobilization of lead from bone compartments, even at low blood lead levels. Subgroups of women who incurred substantial exposures to lead prior to pregnancy should be considered to be at increased risk.     

Effects of excess dietary selenite on lead toxicity in sheep

The hypothesis that excess dietary selenite ameliorates lead (Pb) toxicosis in domestic sheep was tested. Twenty 6–8-yr-old ewes fed alfalfa pellets were assigned to the following treatments: (1) control; (2) 9.8 mg Pb/kg body weight (b.w.)/d as PbCO₃; (3) 3 mg Se/animal/d as Na₂SeO₃·5H₂O; or (4) a combination of treatments 2 and 3. The gelatin-encapsulated salts were given orally. The study was terminated on d 104, by which time three animals in the Pb group and all five animals in the Pb+Se group had died. All remaining animals were slaughtered on d 104. Lead and Se concentrations were determined in six biweekly-collected blood samples and in soft tissues and bone. Sheep on the control and Se treatments had similar feed intakes, body weights, and tissue Pb levels. Those in the Pb+Se group had lower feed intake, but higher blood Pb values compared with the Pb group. Feeding either element increased (P<0.05) the concentration of that element in blood, kidney, liver, spleen, and bone. Muscle-Pb concentrations were not affected (P<0.05) by treatment. Selenium concentrations in kidney, liver, and muscle were greater (P<0.05), whereas those in heart were less (P<0.05) for the Pb+Se group than for the Se Group. Clinical signs associated with Pb toxicosis noted in other animals were not observed in the poisoned sheep in this study. Selenite did not protect sheep against Pb toxicity and likely served as a synergistic factor.     

Lead toxicity in mice embryos]

Administration to female mice before co?tus and to pregnant female mice of an alimentation containing 0.1 p. 100 lead acetate imparied the fertility. Studies on the changes of the ultrastructure of the embryos during the first stages of development do not allow to detect lesions unless on day 7 where lead inclusions are detected in the mitochondria.