Interaction of alcohol and kola nut on brain sodium pump activity in Wistar rats

The effect of interaction of alcohol and kola nut on sodium pump activity was studied in Wistar rats. Thirty Wistar rats were divided into six groups of five rats per group. Control received a placebo (4 mL of distilled water). Groups 2–6 were treated for a period of 21 days with 10% (v/v) alcohol, 50 mg caffeine/kg, 50 mg kola nut/kg, or a combination of 10% (v/v) alcohol + 50 mg kola nut/kg, or 10% (v/v) alcohol + 50 mg caffeine/kg, respectively. One day after the final exposure, brains were harvested and several biochemical parameters examined including activities of total ATPase, ouabain-insensitive ATPase, ouabain sensitive ATPase (Na⁺–K⁺-ATPase) and levels of nonenzymatic breakdown of ATP and inorganic phosphate (P_i) released. Results showed that the essential enzyme of the brain responsible for neuronal function, Na⁺–K⁺-ATPase, was inhibited by alcohol–kola nut co-administration relative to control, resulting in a decreased ATP production, ion transport and action potential, leading to loss of neuronal activities.     

Feasibility of metabolic parameter estimation in pharmacokinetic models of carbon tetrachloride exposure in rats1

Carbon tetrachloride (CCl₄) is a toxic chemical that was once used in degreasers and detergents, and some remnants of the chemical may be present in the water supply. Physiologically-based pharmacokinetic (PBPK) modeling can assist in understanding resulting internal doses of CCl₄ after exposure, but the pharmacokinetic parameters describing the metabolism of CCl₄ are not well characterized. The goal of this study was to provide insights into how to more accurately estimate these values in rats using PBPK modeling and data from previous studies. Three different PBPK models were constructed to describe CCl₄ exposure in rats via inhalation, oral ingestion, and venous injection. Each of these models was compared to data, and sensitivity analysis was performed for each model to determine whether the available data could be used to accurately determine the metabolic parameters of interest. These parameter sensitivities were so low that optimization to the available data yielded physiologically unrealistic results. Model sensitivities were analyzed for different doses and routes of exposure in order to find experimental conditions that would allow for greater identifiability of the metabolic parameters. Data were simulated from these models at optimal conditions with varying levels of noise from a normal distribution. Optimizations were then performed to confirm that the original values could be obtained. The experiments developed are left as suggestions for investigators who wish to further pursue estimating these metabolic parameters.     

Biochemical evaluation of hepatotoxicity in mice due to administration of artemether

Effects of artemether administration on liver and selected biochemical parameters were evaluated. Eighty albino mice were divided into four equal groups. Group 1 was given water which served as control, while groups 2, 3, and 4 were given 1.2, 2.4, or 4.8 mg kg^?1 body weight artemether intramuscularly for five consecutive days. On day 6 all mice were sacrificed by cervical dislocation and blood was collected for analysis of alanine and aspartate transaminases, alkaline phosphatase, copper, and total proteins. Liver tissues were prepared for histological studies. It was found that the serum alanine and aspartate transaminase and alkaline phosphatase activities were higher in groups treated with artemether compared to control. The serum concentrations of copper and total proteins were lower than control. The histological features of liver tissues after administration of artemether showed histopathological alterations. These findings showed that artemether administration may have reversible adverse effects on mouse hepatocytes.     

Toxicological effects of mouse diet contaminated with tributyltin on the immune and neurological systems of C57BL/6 mice

Organotin compounds, widely used as antifouling agents, are known to bioaccumulate in the food chain. Among organotin compounds, tributyltin (TBT), a toxic and widespread contaminant, has become a serious factor in environmental pollution and is suspected of being immunotoxic in animals. The purpose of this study was to assess the effects of 80 µg of TBT per kilogram of body weight (kg bw), provided in food, on the immune and neurological systems of C57Bl/6 mice. Data showed that TBT increased the proliferation of T and B lymphocytes in both adult and juvenile female and juvenile male mice, but that it decreased the proliferation of both T and B lymphocytes in adult male mice. The macrophages activity in female and male juvenile mice was higher than in adults of both sexes. The natural killer cytotoxic activity was also increased in juvenile and adult males and females compared to the control groups. In the brain, we observed the presence of TBT in the hippocampus, the striatum, the cortex, and the cerebellum in both the male and female groups. The highest levels were observed in the cortex of females and males, while the lowest levels were found in the cerebellum. TBT also induced an increase in the levels of the antioxidant glutathione (GSH) in the striatum, the hippocampus and in cortical structures but not in the cerebellum where the levels of TBT are lower. Our findings indicate that TBT modulated the immune and nervous systems causing endocrine and nervous perturbations.     

Interspecific variation of heavy metal concentrations in the different tissues of tropical intertidal gastropods from Malaysia

The present study aims to determine the concentrations of Cd, Cu, Fe, Ni, Pb, and Zn in the different tissues of five species of tropical intertidal gastropods from Malaysia. Each of the species have organs/tissues that highly accumulated certain metals. For Cu, the mantles of Cerithidea obtusa, Pugilina cochlidium, and Murex trapa; and the digestive caeca of Thais sp. and Chicoreus capucinus highly accumulated Cu. The shells of Chi. capucinus and M. trapa, the digestive caeca of P. cochlidium, and the digestive glands of Thais sp. and Chi. capucinus highly accumulated Cd. The tentacles and the digestive caeca of Cer. obtusa and P. cochlidium, respectively, highly accumulated Zn, the digestive glands of Thais sp., Chi. capucinus, and M. trapa also highly accumulated Zn. The shells of most of the gastropods accumulated high levels of Pb and Ni. The opercula of most of the gastropods, besides the digestive glands for Thais sp., accumulated high levels of Fe. The present study on interspecific variations of heavy metals in gastropods provided information on differences of metal distributions in the different tissues, which could be useful in proposing potential tissues as better biomonitoring tools of heavy metal bioavailabilities in the coastal waters of Peninsular Malaysia.     

Biochemical assessment of lead,phenol, and benzene-contaminated water on the heart and blood of Albino rats

A study was performed to evaluate the effect of contaminated water on the tissues of Rattus novergicus (albino rats). Test rats were given water contaminated with lead (0.015 µg L^?1 tap water), phenol (0.05 mL L^?1 tap water), and benzene (0.05 mL L^?1 tap water), while control rats were given tap water over a period of 65 days after which the activity of selected enzymes of the heart and serum was assayed, and hematological parameters and serum lipid profiles were also determined. Generally, a significant (p < 0.05) drop in the activity of the enzymes was observed in the heart of test rats relative to the control rats. However, the serum activities increased significantly in the test group compared to the control group (p < 0.05). The concentrations of serum cholesterol, low-density lipoprotein (LDL), and triglycerides of the test rats were found to be significantly higher than those of the control rats (p < 0.05). Concentrations of hemoglobin, red blood cell count, and packed cell volume of test rats were observed to be significantly lower than those of the control rats (p < 0.05). The experimental results indicated that consumption of water contaminated with lead, phenol, and benzene may damage the heart, increase the risk of atherosclerosis as reflected by the serum lipid profile, and anemia as suggested by abnormal hematological properties.     

Gulf War agents trigger discrete transcriptional changes in human neuronal cells

Reports on Gulf War illness (GWI) implicated the use of the pesticide permethrin (PER), and the insect repellent N,N-diethyl-m-toluamide (DEET), in its etiology, as well as pyridostigmine bromide (PB), which was given as a prophylactic treatment against nerve agent exposure. Using Affymetrix microarrays the genomic response of human neuronal SHSY-5Y cells to 10 days of exposure to these agents was characterized and profiles of gene modulation unique to each treatment were demonstrated. In particular, a significantly greater impact of PER was observed compared to the other treatments. The Ingenuity Pathway Analysis knowledgebase was used to analyze the genomic datasets and attribute functional consequences to the effects of related genes, which were significantly up- or down-regulated in response to different treatments. Canonical pathways shown to be significantly modulated at the genomic level in response to exposure included cellular mechanisms, which might contribute to the clinical presentation in GWI patients and thus be targeted for further investigation as potential targets for therapeutic intervention.     

The status of heavy metal levels in a Ramsar site,Kuala Gula bird sanctuary: the impact of the anthropogenic inputs

Distributions of Cd, Cu, Pb, and Zn in the surface sediments from two sites of the Kuala Gula Bird Sanctuary, Malaysia were monitored for a period of 6 months from October 2006 to March 2007. In December 2006, the concentration of Zn in one location was significantly (p??1) than the other metals at both sites, but in the oxidizable organic fraction it was highest at both sites during October; with mean concentrations of 18?mg?kg^?1 at both locations. In the acid-reducible fraction, high concentrations of Pb (2.3?mg?kg^?1) were detected at station 2 in February 2007, being highest among all four metals at both stations. The acid-reducible fraction found in Pb ranged from 0.10% to 3.1% in both stations. Percentages ranging from 51% to 96% were observed for all four metals in the resistant fraction throughout the sampling period. These results indicate low contributions from anthropogenic sources. The findings constitute a baseline data archive for future reference.     

Immunoprotective effect of curcumin on cypermethrin-induced toxicity in rats

Immunotoxicological effects of cypermethrin and their reversal by curcumin following oral administration were evaluated in rats. Mature male Wistar rats were orally administered cypermethrin (25?mg?kg^?1 body wt), curcumin (100?mg?kg^?1 body wt) or both daily for 4 weeks. At the end of fourth week, hematological, serum biochemical, and immunological parameters were studied. Subchronic exposure to cypermethrin significantly reduced body weight, total leukocyte count, lymphocyte count, serum total protein, serum albumin, serum globulin, antibody titer against sheep red blood cells, and cell-mediated immunity. Concomitant curcumin administration restored the changes in the body weight, hematological parameters, and serum biochemical indices and significantly increased the antibody titer, and cell mediated immunity. These results suggest that concurrent curcumin treatment has a beneficial role in mitigating immunotoxicological and other adverse effects of cypermethrin.