Copper-mediated oxidative stress in rat liver

Copper is an essential trace element with various biological functions. Excess copper, however, is extremely toxic, leading to many pathological conditions that are consistent with oxidative damage to membranes and molecules. Exposure to high levels of copper results in various changes in the tissues. In liver, hypertrophy of hepatocytes, hepatitis, hepatocellular necrosis, and hepatocellular death are the results. Lipid peroxidation causes dysfunction in the cell membrane, decreased fluidity, inactivation of receptors and enzymes, and changes ion permeability. In this study, we aimed to determine the effect of copper on oxidative and antioxidative substances in plasma and liver tissue in a rat model. Sixteen male Sprague—Dawley rats were divided into two groups: Group 1 rats included control rats given tap water. Group 2 rats were given water containing copper in a dose of 100 μg/mL. All rats were sacrificed at 4 wk under ether anesthesia. Plasma and liver superoxide dismutase (SOD) activities, plasma and liver MDA (malondialdehyde) levels, and liver glutathione (GSH) levels were studied. Plasma and liver SOD activities were found to be higher in group 2 than those in group 1. Although plasma MDA levels were higher in group 2, MDA levels in liver tissues were comparable. Liver tissue glutathione levels were lower in group 2. It was concluded that although copper is needed in trace amounts, an excess amount is toxic for the organism. It increases lipid peroxidation and depletes GSH reserves, which makes the organism more vulnerable to other oxidative challenges.     

Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats

BACKGROUND Despite overt insulin resistance,adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids.AIM To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide,since it is produced by monoamine oxidase(MAO)and semicarbazide-sensitive amine oxidase(SSAO)in adipocytes.METHODS 3H-2-deoxyglucose uptake(2-DG)was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine.14C-tyramine oxidation and binding of imidazolinic radioligands[3H-Idazoxan,3H-(2-benzofuranyl)-2-imidazoline]were studied in adipocytes,the liver,and muscle.The influence of in vivo administration of tyramine+vanadium on glucose handling was assessed in lean and obese rats.RESULTS 2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats,when compared to their lean littermates.Tyramine and benzylamine activation of hexose uptake was vanadate-dependent and was also limited,while MAO was increased and SSAO decreased.These changes were adipocyte-specific and accompanied by a greater number of imidazoline I2 binding sites in the obese rat,when compared to the lean.In vitro,tyramine precluded the binding to I2 sites,while in vivo,its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese CONCLUSION The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site number.However,probably as a consequence of SSAO down-regulation,the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant adipocytes.The adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.     

The effect of vaginal candidiasis on the levels of the oxidative biomarkers in plasma and tissue samples of diabetic rats

The aim of this study is to determine the relation between diabetes and vaginal candidiasis in terms of oxidative biomarker levels in a vaginal candidiasis model of the diabetic rats by evaluating malondialdehyde (MDA), sulphydrile groups or glutathione (RSH), and ascorbic acid (C vit) levels. All rats were randomly divided into five groups. All of the groups were observed for 21 days. In the treated diabetes groups, MDA (0.90, 0.68 nmol/ml and 3.78, 3.79 nmol/g tissue, plasma and vaginal tissue, respectively) and RSH (227, 171 nmol/100 ml 0.38, 0.37 μmol/g tissue, plasma and vaginal tissue, respectively) levels were found to be decreased while the levels of C vit were found to be increased (0.49, 0.37 μmol/l 2.39, 2.01 nmol/g tissue plasma, and vaginal tissue, respectively) (P < 0.05). In the groups of untreated diabetes, vaginal candidiasis were found to be more serious and oxidative biomarkers were found to be increased (MDA 1.30, 1.26 nmol/ml and 7.82, 2.37 nmol/g tissue and RSH 258, 145 nmol/100 ml and 0.31, 0.46 μmol/g tissue) while the antioxidant C vit levels were found to be decreased (0.24, 0.17 μmol/l 1.33, 2.66 nmol/g tissue) (P < 0.05). RSH, plasma MDA, blood glucose, and tissue MDA levels of vaginal candidiasis embedeled diabetic rats, were found to be higher than those in untreated diabetic and untreated vaginitis enbedeled rats ‹P < 0.05’. Vaginal candidiasis caused oxidative stress in diabetic rats working together. Systemic oxidative stress biomarkers were found to be affected from vaginal candidiasis although it was a local mucosal infection. This study was presented as a poster in the conference of ‹2nd Trends in Medical Mycology, 23–26 October 2005, Berlin, Germany’.     

Acylceramides and lanosterol-lipid markers of terminal differentiation in cultured human keratinocytes: Modulating effect of retinoic acid

Summary Epidermal differentiation is accompanied by profound changes in the synthesis of a variety of intracellular proteins and intercellular lipids. In conventional, submerged culture keratinocytes have been shown to lose the ability to synthesize the protein markers of differentiation. They re-express them, however, when they are cultured in medium supplemented with delipidized [retinoic acid (RA)-depleted] serum or in air-exposed cultures using de-epidermized dermis (DED) as a substrate. Recent studies have revealed that acylceramides (AC) and lanosterol (LAN), which are present only in trace amounts in cultures of keratinocytes grown under submerged conditions on DED in medium supplemented with normal serum, become expressed in significant amounts when the culture is lifted to the air-liquid interface. Inasmuch as culture conditions may markedly affect the extent of keratinocyte differentiation, the present study aimed to investigate the effect of normal (RA-containing) or delipidized (RA-depleted) serum and of RA administration on lipid composition (especially of the AC and LAN contents) in cells cultured under submerged and air-exposed conditions. To test a possible effect of dermal substrate (used in the air-exposed model), the lipid composition of keratinocytes grown under submerged conditions on a plastic and on a dermal substrate (de-epidermized dermis, DED) has also been compared. The results revealed that under all culture conditions, RA deprivation of fetal bovine serum resulted in a marked increase of total ceramide content. Even under submerged conditions, the presence of both AC and LAN could be detected. In air-exposed culture, the content of these lipids was markedly increased. Addition of RA at 1 μM concentration to cultures grown in RA-depleted medium induced marked changes in lipid composition under all culture conditions tested. In cells grown under submerged conditions (both on plastic and on DED) AC and LAN were no longer present in detectable amounts. Also in air-exposed culture, a marked decrease in the content of these lipids was observed. These results suggest that liposoluble serum components, like RA, control the synthesis of lipids that are present in later stages of epidermal differentiation.     

Cadmium-induced liver, heart, and spleen lipid peroxidation in rats and protection by selenium

The purpose of this study was to evaluate the effects of cadmium-induced peroxidative damage to rat liver, heart, and spleen. Sprague-Dawley rats were injected subcutaneously with a single dose of 25, 125, 500, or 1250 μg Cd/kg and evaluated 6, 12, 24, or 72 h later. Liver, heart, and spleen were analyzed for lipid peroxidation and Fe, Cu, Zn, Se, and Cd concentrations. Data showed that Cd produced enhanced lipid peroxidation in the liver, heart, and spleen. These Cd-induced changes were accompanied by a significant rise in liver, heart, and spleen Fe and Cu, and a fall in spleen Zn and liver, heart, and spleen Se. Concurrent treatment with Se and Cd reduced the Cd-induced alterations in liver, heart, and spleen peroxidation and essential metal levels. Data suggest that lipid peroxidation is associated with cadmium toxicity and that Se was found effective in preventing lipid peroxidation.     

Effect of long-term Se deficiency on the antioxidant capacities of rat vascular tissue

Selenium (Se) is an essential micronutrient in human health and Se deficiency has been incriminated in the etiology of cardiovascular diseases. However, the effect of long-term Se deficiency on the antioxidant capacities of vascular tissue has not been elucidated. This study was to determine whether long-term Se deficiency might affect the antioxidant capacity of rat vascular tissue and whether the diet Se might affect the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR) in rat vascular tissue. Weanling male Wister rats were fed Se-deficient and Se-adequate diets for 12 mo. Se was supplemented in drinking water (1 μg Se/mL) for 1 mo. The arterial walls isolated from various groups were used in the assay. In comparison with the control, Se-deficient rats exhibited significant decreases of GPx activity and total antioxidant capacity in the arterial wall. Similar decreases appeared in the heart, liver, and kidney. The superoxide dismutase activity was also decreased in the Se-deficient rat’s arterial wall. Followed by Se supplementation, they were restored to different extent. TR activity was decreased in the heart, liver, and kidney, but increased in the arterial wall. The content of malondialdehyde was increased markedly in Se-deficient rats. In conclusion, a positive correlation exists between dietary Se and antioxidant capacity of rat vascular tissue except TR. It seems that the activities of GPx and TR in the rat arterial wall were mediated in different pathways by the Se status.     

Adiponectin decreases plasma glucose and improves insulin sensitivity in diabetic Swine

To investigate the effects of recombinant human adiponectin on the metabolism of diabeticswine induced by feeding a high-fat/high-sucrose diet (HFSD),diabetic animal models were constructedby feeding swine with HFSD for 6 months.The effects of recombinant adiponectin were assessed bydetecting the change of plasma glucose levels by commercially available enzymatic method test kits andevaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinantadiponectin was produced using a 15-liter fermenter.A single injection of purified recombinant humanadiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin,which triggered atransient decrease in basal glucose level (P<0.05).This effect on glucose was not associated with anincrease in insulin level.Moreover,after adiponectin injection,swine also showed improved insulin sensitivitycompared with the control (P<0.05).Adiponectin might have the potential to be a glucose-lowering agentfor metabolic disease.Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolismcould be useful to treat insulin resistance.     

Feeding of a low-zinc diet lowers the tissue concentrations of alpha-tocopherol in adult rats

Previous work has shown that a low dietary intake of zinc for a short duration significantly lowers the lymphatic absorption of α-tocopherol (αTP) in adult male rats. The present study investigated whether the nutritional status of zinc is critical in maintaining the tissue levels of the vitamin. One group of rats was fed an AIN-93G diet containing 3 mg zinc/kg (low zinc, LZ) and the other was fed the same diet but containing 30 mg zinc/kg (adequate zinc, AZ). Food intakes between groups were matched by feeding two meals per day. At 6 wk, the body weights (356±8 g) of LZ rats reached 98% those (362±10 g) of AZ rats. Feeding of the LZ diet for 6 wk significantly lowered the concentrations of both αTP and zinc in the liver, kidney, heart, testis, and brain. No consistent relationships between αTP and zinc concentrations were observed in other tissues such as spleen, lung, gastrocnemius muscle, and retroperitoneal fat tissues. The concentrations of αTP in the liver, testis, brain, spleen, heart, and kidney were significantly correlated with the tissue concentrations of zinc. The LZ diet slightly but significantly increased the total lipid contents (mg/g) of liver, kidney, heart, and spleen. However, the tissue levels of phospholipid (μmol/100 mg lipid) in the heart, lung, testis, and spleen were decreased significantly in LZ rats. These findings indicate that low zinc intake results in a pronounced decrease in the animal’s αTP status under the conditions of matched food intakes, body weights, and feeding patterns. The lower tissue levels of αTP may explain in part the compromised antioxidant defense system and increased susceptibility to oxidative damage observed in zinc deficiency.     

Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis

Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin- induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mito- chondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin （HFD/STZ）-induced diabetic mice daily for 4 weeks. Body weight （BW）, fasting blood glucose （FBG） level, and glucose disposal （IPGTT） were measured during or after the treatment. The results showed a dose-dependent re- duction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total chol- esterol and triglyceride levels in the diabetic mice. In add- ition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol （200 mg/kg） rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 （PGC1） α was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol. resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal musde of HFD/STZ-induced diabetic mice.     

Pyrrolidine dithiocarbamate protects pancreatic β-cells from oxidative damage through regulation of FoxO1 activity in type 2 diabetes rats

Pyrrolidine dithiocarbamate （PDTC） can lower the bloot glucose level and improve the insulin sensitivity in diabeti, rats. However, the mechanisms underlying this effect o PDTC treatment in diabetic rats remained uncertain, h this study, we evaluated the mechanisms by which PDT（ conferred protection against oxidative damage to pancreat ic islet β-cells in rats with experimental type 2 diabete mellitus （DM）. DM in the rats was elicited by long-tern high-fat diet accompanied with a single intraperitonea （i.p.） injection of a low dose of streptozotocin. After a 7-da1 administration of PDTC （50 mg/kg/day i.p.）, blood glucos levels were measured and pancreatic tissues were collecte / for the determination of various biochemical and enzyma 1 ic activities using immunohistochemistry, immunofluoresI cence, and western blot techniques. The percentage o 1 apoptotic pancreatic islet β-cells was detected by flow cyto metry. The results showed that diabetic rats had elevate blood glucose levels and insulin resistance, accompanieq with an increase in malondialdehyde content, nitrotyrosin production, and inducible nitric oxide synthase expression A decrease in superoxide dismutase and glutathione pero idase activities was also observed in DM rats, culminatin with elevated β-cell apoptosis. PDTC treatment significantl reduced the oxidative damage and the β-cell apoptosi and also increased the insulin production through down-reg lating FoxO1 acetylation and up-regulating nuclear PDX- level. These data suggested that PDTC can protect islet βcells from oxidative damage and improve insulin productio through regulation of PDX-1 and FoxO1 in a DM rat model.     

Sterol metabolism and oral epithelial cell growth

Summary Previous studies have demonstrated that as the density of cultured oral epithelial cells increases, there is a concomitant increase in phospholipids and cholesterol ester synthesis and a decrease in that of cholesterol and sterol precursors. Other studies have suggested that the effects of exogenous cholesterol sulfate may be similar to growth responses and influence metabolic steps related to cell density. To further examine this possibility, in the present study lipid synthesis was monitored in hamster cheek pouch epithelial cells in cultures established at different cells densities and in the presence of varying amounts of exogenous cholesterol sulfate. Cell [¹⁴C]acetate incorporation into lipids was measured in cultures established at four densities ranging from very subconfluent to very dense (postconfluent) in two media, Dulbecco’s modified Eagle’s medium (DMEM) with 5% fetal bovine serum and KSFM, a non-serum containing keratinocyte medium. Results indicated that the relative proportion of radiolabel incorporated into different lipid classes changed with cell density. In DMEM, the percentage of radiolabel incorporated into total phospholipids and fatty acids increased significantly with increasing cell density whereas percent incorporation into cholesterol, sterol precursors, and cholesterol esters significantly decreased. In KSFM cultures, proportionate phospholipids labeling was significantly increased in more dense cultures whereas cholesterol and cholesterol esters labeling was significantly decreased. In subconfluent and confluent cultures exposed to 10 or 25μM cholesterol sulfate, the relative proportions of phospholipid labeling also increased significantly compared to dimethyl sulfoxide (solvent) controls, whereas sterol precursors, fatty acids, and cholesterol esters labeling was signifcantly decreased. These results indicate that cholesterol sulfate can affect cellular lipid synthesis in a manner similar to that which occurs with increasing cell density, and strengthen the hypothesis that cholesterol sulfate may regulate lipid metabolic pathways related to growth and differentiation.     

Decreased serum brain-derived neurotrophic factor in Chinese patients with Type 2 diabetes mellitus

Brain-derived neurotrophic factor （BDNF） is a member of neurotrophin family associated with the proliferation, differentiation, activity-dependent plasticity, and survival of neurons in the central nervous system [1]. BDNF influences glucose metabolism and insulin sensitivity. For example, BDNF decreases serum glucose, insulin, and HbAlc levels in diabetic rats, suggesting that the BDNF may improve insulin sensitivity. In addition, animal models showed that BDNF levels in the central nervous system are highly related to peripheral serum BDNF levels [2]. It was found that BDNF may ameliorate glucose metabolism and prevent pan- creatic exhaustion in obese diabetic mice [3].     

Glut-4 is translocated to both caveolae and non-caveolar lipid rafts, but is partially internalized through caveolae in insulin-stimulated adipocytes

Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this process, caveolae were ablated by caveolin-1 RNA interference. In Cav-1 RNAi adipocytes, neither insulin-stimulated glucose uptake nor Glut-4 （glucose transporter 4） translocation to membrane lipid microdomains was affected by the ablation of caveolae. With a modified sucrose density gradient, caveolae and non-caveolar lipid rafts could be separated. In the wild-type 3T3- L l adipocytes, Glut-4 was found to be translocated into both caveolae and non-caveolar lipid rafts. However, in Cav1 RNAi adipocytes, Glut-4 was localized predominantly in non-caveolar lipid rafts. After the removal of insulin, caveolaelocalized Glut-4 was internalized faster than non-caveolar lipid raft-associated Glut-4. The internalization of Glut-4 from plasma membrane was significantly decreased in Cav-1 RNAi adipocytes. These results suggest that insulin-stimulated Glut-4 translocation and glucose uptake are caveolae-independent events. Caveolae play a role in the internalization of Glut-4 from plasma membrane after the removal of insulin.     

Serum α-tocopherol and selenium in belgian infants and children

Previous studies showed low selenium (Se) concentrations in Belgian children. Serum α-tocopherol, retinol, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, selenium (Se), and thiobarbituric acid-reactive substances were examined. In order to obtain further information on the Se status in Belgian children, Se, α-tocopherol, retinol, and lipid concentrations were examined and signs of peroxidative lipid damage were evaluated in a subgroup. The study was performed in 524 children (0–14 yr old) during vaccination campaigns. Three age groups were analyzed: 0–1, 1–4, and 4–14 yr. In 87 of them, where sufficient amounts of serum were available, analysis of thiobarbituric acid-reactive substances was done. Infants have high serum α-tocopherol concentrations: (23.2 μmol/L [median and interquartile range: 18.6–30.2]) and low Se concentrations (0.37 mol/L [0.27–0.47]). Se concentrations rise significantly during the first 4 yr (p < 0.0001) (Mann-Whitney U-test, tied p-values): 0.70 μmol/L (0.59–0.82); in the 4–14 yr olds, it was 0.75 μmol/L (0.67–0.86). These values remain low compared to results coming from other parts of the world. α-Tocopherol concentrations decrease significantly after infancy (p < 0.0001). The ratio α-tocopherol/total cholesterol is higher in infants. This is induced by the high vitamin E content of infant formulas. Signs of serum lipid peroxidation could not be detected by analysis of serum malondialdehyde concentrations. High α-tocopherol concentrations, as those observed in infant serum lipids, could be one of the protective mechanisms from the peroxidative lipid damages, sometimes observed in a low-Se status.     

Effect of ozone produced from antibody-catalyzed water oxidation on pathogenesis of atherosclerosis

Recent studies have suggested that antibodies can catalyze the generation of unknown oxidantsincluding hydrogen peroxide (H_2O_2) and ozone (O_3) from singlet oxygen (~1O_2) and water.This study is aimedto detect the effect of antibody-catalyzed water oxidation on atherosclerosis.Our results showed that bothH_2O_2 and O_ were produced in human leukemia THP-1 monocytes incubated with human immunoglobulin Gand phorbol myristate acetate.In the THP-1 monocytes incubated with human immunoglobulin G,phorbolmyristate acetate and low density lipoprotein the intracellular total cholesterol,free cholesterol,cholesterylester and lipid peroxides clearly increased,and a larger number of foam cells were observed by oil red Ostaining.The accumulation of all intracellular lipids was significantly inhibited by vinylbenzoic acid,and onlyslightly affected by catalase.These findings suggested that the production of O_3,rather than H_2O_2,might beinvolved in the pathogenesis of atherosclerosis through the antibody-catalyzed water oxidation pathway.     

Association between serum somatostatin levels and glucose-lipid metabolism in the Jino ethnic minority and Han Chinese population

We aim to investigate the relationship between serum somatostatin(SST) levels and glucose-lipid metabolism at various stages of glucose tolerance in the Jino ethnic minority(n=111) and Han population(n=113) of Yunnan Province, southwest China.Anthropometric parameters and biochemical traits were measured. Serum SST and plasma glucagon levels were tested. Participants were divided into three subgroups: isolated fasting hyperglycemia(IFH), isolated post challenge hyperglycemia(IPH)and normal glucose tolerance(NGT). SST levels were found lower while glucagon levels were significantly higher in the Jino ethnic with IPH(P=0.0026 and P=0.0069, respectively). Fasting glucose and high density lipoprotein-cholesterol(HDL-C)levels were higher(P=0.0055 and P=0.0021, respectively) and fasting insulin levels and homeostasis model assessments β-cell function were lower(P=0.0479 and P=0.0007, respectively) in the Jino population. After adjusting for confounding factors, the serum SST level was associated with glucagon(P0.0001) in both populations. The SST level was correlated with fasting Cpeptide(P=0.0267) in Jino and HDL-C levels in Han(P=0.0079). Our findings suggest that serum SST levels and plasma glucagon levels may vary in subjects with IPH between two ethnics.     

Association of different zinc concentrations combined with a fixed caffeine dose on plasma and tissue caffeine and zinc levels in the rat

Because caffeine and tissue levels of Zn are closely related, the objectives of this study were to determine the changes in plasma caffeine levels over a period of 5 h when different concentrations of Zn combined with a fixed concentration of caffeine were injected into the femoral vein of rats and to determine the relationship between tissue levels of caffeine and Zn at 5 h postinjection. Rats were divided into three groups: group 1, 220 μg caffeine; group 2,220 μg caffeine + 8 μg Zn/g body weight (BW); group 3, 220 μg caffeine +16 μg Zn/g BW. Blood from groups 1 and 3 was collected at 3 min, 30 min, 1h, 3h, and 5h to determine the pharmacokinetics of caffeine. All groups were killed at 5 h. Caffeine and Zn concentrations of the brain, kidney, heart, and liver of all groups were determined. The plasma-caffeine curve in group 3 showed a lower concentration at 3 min and a slower caffeine-elimination rate during the first 3 h. Brain and kidney caffeine levels remained constant in all groups, whereas caffeine levels were increased in the heart in group 2 and in the liver in group 3. Zn concentrations in the brain and kidney were lower in group 2 compared with groups 1 and 3 and higher in group 3 compared to groups 1 and 2. Zn concentration in the heart was the same among the three groups but was increased in the liver in group 3 compared to groups 1 and 2. Therefore, we concluded that caffeine combined with Zn affects caffeine pharmacokinetics. With caffeine intake, levels of Zn (16 μg/g BW) that are slightly higher than the daily requirements (12 μg/g BW) may prevent a reduction of Zn in tissue. In addition, caffeine’s effects on Zn concentration among organs are different.     

Prophylactic effect of vitamin E against hepatotoxicity,nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

Considering that the involvement of reactive oxygen species （ROS） has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E （100 mg/kg body weight） on mice （25 -30 mg） treated with diazinon （32.5 or 16.25 mg/kg body weight） organophosphate insecticide for 14 days. Subehronic DZN exposure and the protective effects of vitamins E （vitE） were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase （ ALT）, aspartate aminotaransferase （ AST）, alkaline phosphatise （ ALP）, and some parameters of kidney function （urea and creatinine） in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon （DZNH） decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significandy. Moreover, there was a statistically significant decrease in haemoglobin （Hb）, red blood cell （RBC） and hematocrit （Hct） in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE ＋ DZNtreated groups. According to the present study, we conclude that vitE ean reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function [ Current Zoology 55 （3） ： 219 - 226, 2009].     

Effect of long-term treatment with vanadate in drinking water on KK mice with genetic non-insulin-dependent diabetes mellitus

The glucose-lowering effect of vanadate, ammonium metavanadate (AMV), on diabetic KK mice was examined. Five-week-old male KK mice were administrated with a solution of AMV via drinking water at concentrations of vanadium (V) with 0.1, 1.0, 10 and 100 μg/mL for a period of 10 wk, respectively. Body weight, consumption of food and water, and blood glucose levels was measured every week for 10 wk. The results showed that food consumption and body weight in the experimental groups were similar to those in the control group. A statistically significant decrease of drinking water consumption and blood glucose levels in the group treated with 100 μg V/mL was observed. The glucose tolerance in the vanadate-treated mice with 10 and 100 μg V/mL was remarkably improved compared with the control group. Biochemical analyses at the end of experiments demonstrated that a distinct tendency for the glucose and hemoglobin A1c (HbA1c) levels to decrease with vanadate treatment in the blood was also observed. The glutamic pyruvic transaminase, glutamic oxaloacetate transaminase, blood urea nitrogen, triglyceride, high-density lipoprotein, and total cholesterol levels in plasma were lower in the higher vanadium groups than those in the control group. These results indicate that vanadium effectively produced the glucose-lowering effect at a higher dose than that at a low dose of vanadium in drinking water, without any overt signs of toxicity.     

Excessive hepatic copper accumulation in jaundiced rats fed a high-copper diet

The response of copper metabolism to dietary copper challenge was investigated in jaundiced rats with elevated plasma concentrations of conjugated bilirubin as a result of impaired canicular transport of bilirubin glucuronides. Control and jaundiced rats were fed purified diets with either normal (64 μmol Cu/kg) or high (640 μmol Cu/kg) concentration of added copper. Copper loading produced a greater increase in hepatic copper concentrations in the jaundiced than in control rats. The greater dietary-copper-induced increase in hepatic copper in the jaundiced rats can be explained by the observed smaller rise in biliary copper excretion and a greater efficiency of dietary copper absorption. In individual rats, there was a positive relationship between hepatic copper concentrations and biliary copper concentrations. It is suggested that not the transport of copper from liver cells to bile but that from plasma to bile is diminished in the jaundiced rats. The elevated plasma copper concentrations in the jaundiced rats may support this suggestion.