Effect of Ginkgo biloba Extract on Lead-Induced Oxidative Stress in Different Regions of Rat Brain.

Ginkgo biloba extract (GbE) is a well known natural antioxidant. In the present investigation, its ameliorative effects were tested against lead-induced oxidative stress in rat brain. Four groups of male Wistar rats (100 to 120 g) were used, consisting of eight rats per group. Rats in the control group received 500 ppm of sodium acetate through drinking water, and rats in the other three groups received 500 ppm of lead acetate through drinking water for 4 weeks. Rats in the third and fourth groups were administered (oral) 50 and 100 mg/kg of GbE, respectively, along with lead acetate. The rats were sacrificed after treatment and brains were isolated. Each brain was dissected on ice, and different regions, namely the cerebellum, hippocampus, frontal cortex, and brainstem, were separated. The results revealed a significant (P < .001) increase in reactive oxygen species, catalase, superoxide dismutase, lipid peroxidation products, and total protein carbonyl content, relative to their controls, in all four regions of the brain exposed to lead. These results indicate oxidative stress. Partial restoration was observed for all the parameters just mentioned in different brain regions on treatment with 50 mg/kg GbE. This amelioration was higher with 100 mg/kg GbE, showing dose-dependency. Overall the data suggest that GbE protects against lead-induced oxidative stress in specific regions of rat brain.

Carotenoid as a sensitive indicator of sub lethal cadmium toxicity in Penaeus monodon post larvae.

The objective of the present study is to evaluate a sensitive indicator of cadmium by measuring oxygen consumption and carotenoid concentration in post larvae of Penaeus monodon. The post larvae of P. monodon were exposed to 0.12 and 0.24 mg/L of cadmium in the laboratory for a period of 30 days. These concentrations represent 1/10th and 1/5th of 96 h LC50 value for the post larvae. Oxygen consumption and carotenoid concentration were measured at 24, 48, 96 h, 10 and 30 days of cadmium exposure. The results indicated an inhibition of routine oxygen consumption in post larvae at different intervals of exposure from 24 h to 30 days but the effect was statistically significant (P < 05) at 30 days of exposure at both sub lethal concentrations, where the inhibition was 38.5 % at 0.24 mg/L and 21.6 % at 0.12 mg/L. On the other hand, carotenoid concentrations increased gradually with increasing period of exposure as well as concentration, and this increase was statistically significant (P < 0.05) from 96 h onwards on exposure to 0.12 mg/L and from 48 h onwards on exposure to 0.24 mg/L of cadmium, with an overall highest increase of 135 %. As carotenoid content is an indicator of tissue oxygen, inhibition of routine oxygen consumption might have resulted in enhancing the levels of carotenoid. From the present data, it is evident that carotenoid concentration can be considered as a sensitive indicator of cadmium toxicity than routine oxygen consumption in the post larvae of P. monodon. The present investigation is also relevant for environmental monitoring of cadmium in coastal waters before it is used for aquaculture.

Attenuation of lead-induced oxidative stress in rat brain, liver, kidney and blood of male Wistar rats by Moringa oleifera seed powder.

Moringa oleifera is a tree belonging to Moringaceae family and its leaves and seeds are reported to have ameliorative effects against metal toxicity. In the present investigation, M. oleifera seed powder was tested against lead-induced oxidative stress and compared against meso-2, 3-dimercaptosuccinic acid (DMSA) treatment. Male Wistar rats (100-120 g) were divided into four groups: control (2000 ppm of sodium acetate for 2 weeks), exposed (2000 ppm of lead acetate for 2 weeks), Moringa treated (500 mg/kg for 7 days after lead exposure), and DMSA treated (90 mg/kg for 7 days after lead exposure). After exposure and treatment periods, rats were sacrificed and the brain was separated into cerebellum, hippocampus, frontal cortex, and brain stem; liver, kidney, and blood were also collected. The data indicated a significant (p<0.05) increase in reactive oxygen species (ROS), lipid perioxidation products (LPP), total protein carbonyl content (TPCC), and metal content of brain regions, liver, and kidney in the exposed group compared with their respective controls. In the blood, delta-amino levulinic acid dehydratase (ALAD) activity, RBC, WBC, hemoglobin, and hematocrit showed significant (p<0.05) decrease on lead exposure. However, administration of M. oleifera restored all the parameters back to control, tissue-specifically, and also showed improvement in restoration better than DMSA treatment, indicating reduction of the negative effects of lead-induced oxidative stress.

Hydroalcoholic seed extract of Coriandrum sativum (Coriander) alleviates lead-induced oxidative stress in different regions of rat brain.

Lead exposure is known to cause apoptotic neurodegeneration and neurobehavioral abnormalities in developing and adult brain by impairing cognition and memory. Coriandrum sativum is an herb belonging to Umbelliferae and is reported to have a protective effect against lead toxicity. In the present investigation, an attempt has been made to evaluate the protective activity of the hydroalcoholic extract of C. sativum seed against lead-induced oxidative stress. Male Wistar strain rats (100-120 g) were divided into four groups: control group: 1,000 mg/L of sodium acetate; exposed group: 1,000 mg/L lead acetate for 4 weeks; C. sativum treated 1 (CST1) group: 250 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure; C. sativum treated 2 (CST2) group: 500 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure. After the exposure and treatment periods, rats were sacrificed by cervical dislocation, and the whole brain was immediately isolated and separated into four regions: cerebellum, hippocampus, frontal cortex, and brain stem along with the control group. After sacrifice, blood was immediately collected into heparinized vials and stored at 4 °C. In all the tissues, reactive oxygen species (ROS), lipid peroxidation products (LPP), and total protein carbonyl content (TPCC) were estimated following standard protocols. An indicator enzyme for lead toxicity namely delta-amino levulinic acid dehydratase (δ-ALAD) activity was determined in the blood. A significant (p<0.05) increase in ROS, LPP, and TPCC levels was observed in exposed rat brain regions, while δ-ALAD showed a decrease indicating lead-induced oxidative stress. Treatment with the hydroalcoholic seed extract of C. sativum resulted in a tissue-specific amelioration of oxidative stress produced by lead.

Ameliorative effects of Bacopa monniera on lead-induced oxidative stress in different regions of rat brain.

Bacopa monniera is a rejuvenating herb for brain cells enhancing learning and cognitive ability. In the present investigation, the ameliorative effects of Bacopa monniera were examined against lead-induced oxidative stress in different regions of rat brain. Male rats were divided into five groups: control (1000 ppm sodium acetate) and exposed (1000 ppm lead acetate) for 4 weeks; DMSA (Meso-2,3-Dimercaptosuccinic acid)-treated (90 mg/kg body weight/day); Bacopa monniera-treated (BM) (10 mg/kg body weight/day) and a combination of BM + DMSA for seven consecutive days after 4 weeks of lead exposure. After treatment, the whole brain was isolated by sacrificing rats and four regions were separated namely cerebellum, hippocampus, frontal cortex and brain stem. Results indicated a significant (p < 0.05) increase in reactive oxygen species (ROS), lipid peroxidation products (LPP) and total protein carbonyl content (TPCC) in association with tissue metal content in all the four regions of brain for exposed group compared with their respective controls. However, the lead-induced ROS, LPP, TPCC and tissue metal content were lowered on treatment with Bacopa monniera, almost reaching the control group values in all the above brain regions compared to DMSA and a combination therapy. Results suggest that Bacopa monniera can mitigate the lead induced-oxidative stress tissue specifically by pharmacologic interventions which encompass both chelation as well as antioxidant functions.

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.

Lead-induced increase in antioxidant enzymes and lipid peroxidation products in developing rat brain.

Pregnant rats were treated with 0.4% lead acetate through drinking water from 6th day of gestation and this treatment was continued till 21 post natal days (PND). Four regions of the brain namely hippocampus, cerebellum, frontal cortex and brain stem were dissected at 10, 20, 30 and 40 PND for estimation of lipid peroxidation products (LPP), catalase (CAT) and superoxide dismutase (SOD). The results indicate that there was a significant (P < 0.05) increase of LPP in exposed rats than their corresponding control at 10, 20 and 30 PND both in hippocampus and cerebellum. At PND 40, the LPP of control and exposed were found to be almost same in both the tissues indicating recovery from lead toxicity. CAT activity was significantly (P < 0.05) high in hippocampus of exposed rats up to PND 30 but up to PND 20 in cerebellum and frontal cortex. However, in brain stem, a significant (P < 0.05) increase in CAT activity was observed only at PND 10. A significant (P < 0.05) increase in SOD activity was observed up to PND 30 both in hippocampus and cerebellum on lead exposure. Frontal cortex exhibited a similar significant (P < 0.05) increase of SOD activity up to PND 20 and for brain stem up to PND 10. There was no significant change in the activity of antioxidant enzymes (CAT and SOD) and LPP in all the four brain tissues of control and exposed rats at PND 40 indicating recovery from lead-induced oxidative stress.

Region specific increase in the antioxidant enzymes and lipid peroxidation products in the brain of rats exposed to lead.

The objective of this study is to determine the effect of lead (pb) on antioxidant enzymes and lipid peroxidation products in different regions of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks. Control animals were maintained on sodium acetate. Treated and control rats were sacrificed at intervals of 1st, 4th and 8th week and the whole brains were dissected on ice into four regions namely the cerebellum, the hippocampus, the frontal cortex and the brain stem. Antioxidant enzymes namely catalase and superoxide dismutase in all the four regions of brain were determined. In addition, lipid peroxidation products were also estimated. The results indicated a gradual increase in the activity of antioxidant enzymes in different regions of the brain and this response was time-dependent. However, the increase was more in the cerebellum and the hippocampus compared to other regions of the brain. The lipid peroxidation products also showed a similar trend suggesting increased effect of lead in these two regions of the brain. The data indicated a region-specific oxidative stress in the brain exposed to lead.

In vitro effect of lead on Na+, K+-ATPase activity in different regions of adult rat brain.

Lead interferes with cellular energy metabolism by inhibiting ATP (Adenosine triphosphate) synthesis and hydrolysis. This study was conducted to determine in vitro effects of lead on Na+, K+-ATPase activity in four regions of adult rat brain: the cerebellum, the hippocampus, the frontal cortex and the brain stem. Male rats (Wistar strain) weighing 125-150 g were sacrificed, whole brain excised and the four regions were isolated. Each tissue was homogenized separately in sucrose (0.25 M) and imidazole (10 mM) buffer (pH 7.5) and P2 fraction was prepared by following established methods. The activity of ATPase was determined by measuring inorganic phosphate (Pi) liberated from ATP hydrolysis. The delineation of Na+, K+-activated component of ATPase was obtained by the difference between total ATPase and Mg2+-ATPase using 1 mM ouabain. The P2 fraction was incubated with 0, 5, 10, 25, 50 and 100 microM of lead at 37 degrees C for 10 min. The enzyme activity was expressed as micromoles of Pi liberated/mg protein/hr. The results indicated a concentration-dependent and region-specific response to lead. In vitro lead at 50 and 100 microM significantly inhibited ATPase activity in all regions of the brain. It was also observed that in the control rats, the enzyme activity was high in cerebellum and hippocampus regions of the brain. In vitro dithiothreitol (DTT) protected the enzyme activity from IC50 lead in four regions of brain. In cerebellum and hippocampus, a 5 microM DTT provided 100% protection against IC50 lead. These results suggest that lead interferes with the ion transport mechanism and cellular energy metabolism of the brain and this effect is region specific.

Acute toxicity of lead on tolerance, oxygen consumption, ammonia-N excretion, and metal accumulation in Penaeus indicus postlarvae.

The estuaries and backwaters that are the potential breeding grounds of penaeid shrimps are subject to heavy metal pollution through industrial effluents and domestic sewage. In the present investigation, laboratory experiments were conducted to study the acute toxicity of lead on tolerance, oxygen consumption, ammonia-N excretion, and metal accumulation in Penaeus indicus postlarvae. Static bioassay tests were employed to determine tolerance limits. Oxygen consumption, ammonia-N excretion, and metal accumulation were determined in postlarvae by exposing them to different concentrations of lead for a period of 48 h. Oxygen consumption measurements were made by using a respiratory chamber equipped with an oxygen electrode and ammonia-N was determined with trione (dichloro-S-triamine 2,4,6(1H,3H,5H-trione)). Accumulation of metal was estimated by wet-ash method. The LC50 value for 96 h was 7.223 ppm and the regression equation Y=4.1638+0.9738X with correlation coefficient of 0.9613 was obtained by probit method. A decrease in oxygen consumption and ammonia-N excretion was observed in postlarvae with increasing concentration of lead. A concentration-dependent accumulation of metal was noticed in these postlarvae. Modifications in O:N ratios of postlarvae suggest that lead accumulation might have altered utilization patterns.