Lead-induced cardiac and hematological alterations in aging Wistar male rats: alleviating effects of nutrient metal mixture.

Age related mitochondrial impairments are considered to be contributors of cardiovascular disease. This study was designed to examine whether early life exposure to lead (Pb) would lead to the Pb induced age related hematological and cardiac mitochondrial changes in rats, and to further examine the protective effect of nutrient metal mixture containing zinc, iron and calcium. Male albino rats were lactationally exposed to 0.2 % Pb-acetate or 0.2 % Pb-acetate together nutrient metal mixture (0.02 %) in drinking water of the mother from postnatal day 1 (PND1) to PND 21. The hemoglobin level, the activities of serum ceruloplasmin oxidase, cardiac mitochondrial enzymes catalase, manganese superoxide dismutase, copper zinc superoxide dismutase, glutathione peroxidase, succinate dehydrogenase, lipid peroxidation and Pb levels were analyzed at PND 45, 12 and 24 months age. The hematological parameters, and the cardiac TCA cycle and antioxidant enzyme markers and lipid peroxidation levels were significantly altered following Pb exposure in young rats (PND 45). These Pb induced changes persisted, though at much lower level in the aged rats. The Pb levels in blood and heart were also significantly higher in PND 45 and remained at detectable levels in older rats. The nutrient metal mixture containing iron, calcium and zinc significantly reversed these changes in all the chosen markers except lipid peroxidation in which the reversal effect was not significant. These data are supportive of age-related cardiac mitochondrial impairments and further provide evidence for the protective efficacy of nutrient metal mixture against Pb-toxicity.

Perinatal lead exposure alters postnatal cholinergic and aminergic system in rat brain: reversal effect of calcium co-administration.

Our earlier studies indicated the role of neurotransmitter systems in lead (Pb) induced behavioral perturbations. In this study, we examined the alterations in synaptosomal acetylcholine (ACh), epinephrine, dopamine, acetylcholinesterase (AChE), and mitochondrial monoamine oxidase (MAO) in the cerebellum and hippocampus of perinatally Pb-exposed rats. Rats (Wistar) were exposed to 0.2% Pb (Pb acetate in drinking water of mother) from gestational day 6 and the pups were exposed lactationally (through mother's milk) to Pb till weaning (postnatal day 21). Studies conducted on different postnatal days (PND 21, 28, 35 and 60) showed significant decreases in synaptosomal AChE and mitochondrial MAO activities, and increases in the levels of ACh, dopamine and epinephrine in the cerebellum and hippocampus of Pb-exposed rats. These alterations were greater at PND 35 and more pronounced in the cholinergic system (ACh and AChE) of hippocampus and the aminergic system (epinephrine, dopamine and MAO) of cerebellum. The total locomotor activity and exploratory behavior were also decreased significantly in Pb-exposed animals corresponding to the alterations observed in cholinergic and aminergic systems. Calcium administration together with Pb, however significantly reversed the Pb-induced alterations in transmitters and enzymes, as well as exploratory and motor behavior suggesting protective effect of calcium in Pb-exposed animals.

Developmental exposure to lead and late life abnormalities of nervous system.

Role of developmental exposure to environmental agents in altering the disease process is well known. Exposure to chemical agents at critical periods of development may cause some permanent changes in the functioning of various vital systems including the nervous system in the organisms. It is not surprising to see an extensive response due to exposure to chemical agents early in life as the organ systems are more vulnerable to chemical insults during developmental stages. In some cases the response to low level environmental insults may not be obvious until adult or old age. Results from several studies have shown such latency in response to the nervous system leading to neurodegeneration in old age. Studies conducted in murine and primate models provided ample evidence for the association of developmental exposure to low levels of heavy metal lead (Pb) and Alzheimer's disease-like pathology during senescence. It is not clear about the reasons behind such response; however, the contribution of epigenetic mechanisms could explain the role of early events in life in inducing the late life abnormalities of nervous system. It is possible that environmental agents epigenetically modulate the gene regulation to persist the response silent for a long period of time and to result pathological outcomes significantly later in life. This article will summarize the association of early life exposure to environmental agents and late-life abnormalities with an emphasis on developmental exposure to Pb and neurodegeneration in old age.

Calcium and zinc supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and lipid peroxidation in developing mouse brain.

Several studies have implicated oxidative stress as one of the important mechanisms of toxic effects of lead (Pb). In the present study we tested the beneficial effects of calcium (Ca2+) and zinc (Zn2+) in protecting the Pb-induced oxidative stress in the brains of developing and adult mice. Mice were lactationally exposed to 0.2% Pb and supplemented with either calcium (Ca2+) or zinc (Zn2+) and the mitochondrial antioxidant enzymes [superoxide dismutase (SOD), xanthine oxidase (XO) and catalase (CAT)] and lipid peroxidation (LP) were analyzed in cortex, hippocampus, cerebellum and medulla of brains excised on postnatal day (PND) 14, 21, 28 and 3 months. The levels of free radicals were measured using direct Electron Paramagnetic Resonance (EPR) spectroscopy. Exposure to Pb resulted a significant decrease in the activities of SOD, XO and CAT while the LP levels were significantly increased in different brain regions. Evaluation of EPR signals and g-values showed abundant accumulation of free radicals in different regions of the brain following Pb exposure. Interestingly the supplementation with Ca2+ or Zn2+ reversed the Pb-induced effects on antioxidant enzymes, LP and free radical formation; however Zn2+ supplementation appeared to be more protective. These findings strongly support that zinc and calcium supplementation significantly protect the Pb-induced oxidative stress, a major contributing factor to neurotoxicity.

Alterations in acetylcholinesterase and electrical activity in the nervous system of cockroach exposed to the neem derivative, azadirachtin.

Botanical insecticides are relatively safe and biodegradable, and are readily available sources of bioinsecticides. In recent years, the neem derivative, azadirachtin, has been examined as an alternative to synthetic insecticides because of its broad-spectrum insecticidal action. Because many of the natural products and synthetic compounds used in the control of insect pests are known to exhibit electrophysiological effects, in this paper we focused our studies on the alterations in the activity of the enzyme acetylcholinesterase (AChE) and electrical activity in the nervous system of the cockroach, Periplaneta americana, exposed to azadirachtin. Exposure to azadirachtin produced an excitatory effect on spontaneous electrical activity as well as cercal sensory-mediated giant-fiber responses in the cockroach. Topical exposure to sublethal doses of azadirachtin did not result in any significant alterations in the AChE activity in different regions of the nervous system. We suggest that azadirachtin exerts excitatory action on the electrical activity in the nervous system of cockroach by interfering with the ion channels in the nerve membrane, the probable target of several insecticides.