• Toxicological Research
• /
• v.27 no.3
• /
• pp.143-147
• /
• 2011

Cadmium is considered one of the most toxic, non biodegradable heavy metal for the human and animals. The purpose of the present study was to investigate the changes in biochemical parameters of blood and accumulation of cadmium in various tissue caused by various levels of dietary cadmium chloride ($CdCl_2$) in broiler chicks. $CdCl_2$ was administered through drinking water to broiler chicks. In spectral analysis, $CdCl_2$ treatment caused a significant increase in Glutamate pyruvate transaminase (GPT), creatinine and uric acid levels in all treated groups. Intriguingly, the GPT, creatinine, and uric acid levels were significantly higher at 75 mg/kg as compared to the groups treated with high doses (100, 125 and 150 mg/kg) of $CdCl_2$. Atomic Absorption Spectrophotometer (AAS) was used for the determination of Cd accumulation in kidney, liver and Breast muscles. AAS analysis revealed that Cd accumulation is increased in breast muscles as compared to liver and kidney at higher doses of Cd than 75 mg/kg.

• Journal of Applied Biological Chemistry
• /
• v.56 no.2
• /
• pp.109-112
• /
• 2013

Azole fungicides are one of the most wide-spread antifungal compounds in agriculture and pharmaceutical applications. Their major mode of action is the inhibition of ergosterol biosynthesis, giving depletion of ergosterol, precursors and abnormal steroids. However, metabolic consequences of such inhibition, other than steroidal metabolitesare not well established. Comprehensive metabolic profiles of Saccharomyces cerevisiae has been presented in this study. Wild type yeast was treated either with glucose as control or azole fungicide (ketoconazole). Both polar metabolites and lipids were analyzed with gas chromatography-mass spectrometry. Approximately over 180 metabolites were characterized, among which 18 of them were accumulated or depleted by fungicide treatment. Steroid profile gives the most prominent differences, including the accumulation of lanosterol and the depletion of zymosterol and ergosterol. However, the polar metabolite profile was also highly different in pesticide treatment. The concentration of proline and its precursors, glutamate and ornithine were markedly reduced by ketoconazole. Lysine and glycine level was also decreased while the concentrations of serine and homoserine were increased. The overall metabolic profile indicates that azole fungicide treatment induces the depletion of many polar metabolites, which are important in stress response.

• Fisheries and Aquatic Sciences
• /
• v.14 no.4
• /
• pp.355-361
• /
• 2011

Effects of aluminum (Al) on plasma vitellogenin (VTG), alkaline-labile phosphorus (ALPP), calcium (Ca), glutamate pyruvate transaminase (GPT), the hepatosomatic index (HSI), and hepatic Al concentration were examined in estradiol-$17{\beta}$ ($E_2$)-administered immature rockfish Sebastes schlegeli. Fish were injected intraperitoneally with $E_2$ (5 mg/kg body weight [BW]) and/or Al (0, 0.1, 1, 5, and 10 mg/kg BW) and plasma and liver samples were extracted 7 days later. After sodium dodecyl sulfate polyacrylamide gel electrophoresis, the relative amount of VTG was determined by integrated optical density. VTG accounted for 23.6% of the total proteins in the control group, but this value decreased with increasing Al administration. Al reduced the concentrations of ALPP and Ca in a concentration-dependent manner and significant reduction occurred at Al concentrations greater than 5 mg/kg. The concentration of GPT increased in a concentration-dependent manner in all Al-administered rockfish. The concentrations of Al in the liver also increased, and HSI was decreased, in a concentration-dependent manner. These results suggest that Al inhibits $E_2$-induced VTG production by being toxic to hepatocytes in marine fish.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.3
• /
• pp.311-319
• /
• 2018

Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (${\Delta}{\psi}_m$). Therefore, pharmacological manipulation of ${\Delta}{\psi}_m$ can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ${\Delta}{\psi}_m$ against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity ($100{\mu}M$, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate ($100{\mu}M$)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of $Ca^{2+}$ ($5{\mu}M$). Nobiletin-induced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ${\Delta}{\psi}_m$ were completely abolished in $K^+-free$ medium on pure isolated mitochondria. Taken together, results demonstrate that $K^+$ influx into mitochondria is critically involved in partial mitochondrial depolarization-related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial $K^+$ influx is probably mediated, at least in part, by activation of mitochondrial $K^+$ channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

• Journal of Applied Biological Chemistry
• /
• v.55 no.2
• /
• pp.123-127
• /
• 2012

In order to develop eco-friendly biopesticide, an entomopathogenic bacterium Photorhabdus temperata M1021 has been lyophilized via freeze-drying along with protective agents such as skim milk, starch, sodium alginate, glucose and sodium glutamate to protect cells from lysis. Freeze-drying powder of P. temperata M1021 containing 7% skim milk (w/v) showed highest survival rate of 63% among all the protective agents used in trials. Furthermore, the freeze-dried microbial powder showed 75% of survival rate after stored at $4^{\circ}C$ for 4 weeks at air contact conditions. Injection toxicity of the freeze-dried sample was tested against larvae of Galleria mellonella. A dose of $2.0{\times}10^1$ cells of P. temperata M1021 killed 100% of the G. mellonella larvae within 4 days after injection. Moreover, $2.0{\times}10^0$ cells caused 50% mortality within the 4 days after injection. Freeze-dried P. temperata M1021 strains exhibited effective insecticidal activity and could be a better candidate for being used as a biopesticide.

• Journal of Life Science
• /
• v.20 no.1
• /
• pp.133-141
• /
• 2010

The protective effect of a mixed powder from solid-cultured and liquid-cultured Lentinus edodes mycelia (2:1, w/w) (designate LED) on the carbon tetrachloride ($CCl_4$)- and ethanol-induced hepatotoxicity of male Sprague-Dawley (SD) rat was investigated. In the $CCl_4$-induced rat hepatotoxicity experiment, rats of 4 groups (6 rats/group) were administere with Normal (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 200 mg/kg BW + 0.2 ml distilled water), and Silymarin (200 mg/kg BW + 0.2 ml distilled water), p.o., daily for 2 weeks. Afterwards, all groups except for the Normal group were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1:1 v/v; 0.5 ml/kg BW). For the ethanol- induced rat hepatotoxicity experiment, rats were divided into 5 groups (5 rats/group): Normal; Pair-fed control (PFC); Control (ethanol); LED (ethanol + LED 200 mg/kg BW); and Silymarin (ethanol + silymarin 200 mg/kg BW). Rats of the Normal and PFC groups were fed a basal liquid diet, and rats of the Control, LED, and Silymarin groups were fed a liquid ethanol diet containing LED or Silymarin. Eight weeks later, blood and liver samples were collected to analyze biomarkers. In $CCl_4$-induced SD rats, LED elevated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH peroxidase) activities and thiobarbituric reactive substances (TBARS) were reduced, resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic dehydrogenase (LDH) activities in plasma. Similar results of these enzymes and biochemical markers in both liver tissues and plasma were seen in ethanol-induced hepatotoxicity of SD rats. In addition, elevated alcohol dehydrogenase (ADH) activity and reduced expression of cytochrome p450 mixed monooxygenase enzyme (CYP2E1) were seen in liver tissues from ethanol-treated rats by LED treatment. These effects of LED were similar to those of Silymarin. In in vitro experiments, LED showed antioxidant activity in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) system and mouse liver mitochondria system induced by NADPH/$Fe^{2+}$ and cumine hydroperoxide (CuOOH). These results indicate that LED protected SD rat hepatotoxicity, induced by $CCl_4$ and ethanol, through its antioxidative activity and might be useful as a material for protection from hepatoxicity in humans.

• Applied Biological Chemistry
• /
• v.18 no.2
• /
• pp.71-97
• /
• 1975

To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

• Development and Reproduction
• /
• v.12 no.1
• /
• pp.1-8
• /
• 2008

Specific protocols to increase the differentiation of neuronal cells from embryonic stem (ES) cells have been well established, such as retinoic acid induction and lineage selection of neuronal cells. For the neuropathological studies, ES-derived neurons (ES neurons) must show normal physiological characteristics related to cell death and survival and should be maintained in vitro for a sufficient time to show insults-specific cell death without spontaneous death. When mouse ES cells were plated onto astrocytes monolayer after retinoic acid induction, most ES cells differentiated into neuronal cells, which were confirmed by the presence of specific neuronal markers, and the cultures were viable for at least four weeks. When these cultures were examined for vulnerability to glutamate excitotoxicity, ES neurons were vulnerable to excitotoxic insults mediated by agonist-specific receptors. The vulnerability to excitotoxic death increased with developmental age of ES neurons in vitro. Specific receptors for Neurotrophin and GDNF family ligands were present in ES neurons. GDNF and NT-3 could modulate the survival and excitotoxic vulnerability of ES neurons. The vulnerability and resistance to toxic insults, which are essential requirements of model culture systems for neuropathological studies, make ES neurons to a useful model culture system. Especially ES cell are highly amenable to genetic modification unlikely to primary neuronal cells, which will give us a chance to answer more complicated neurophysiological questions. Recently there was an outstanding attempt to explore the cellular toxicity using human ES cells (Schrattenholz & Klemm, 2007) and it suggested that ES cells could be a new model system for neurophysiological studies soon and go further a large-scale screening system for pharmacological compounds in the future.

• Journal of Oriental Neuropsychiatry
• /
• v.21 no.2
• /
• pp.125-140
• /
• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.