Intense Exercise Induces Mitochondrial Dysfunction in Mice Brain

There are conflicts between the effects of free radical over-production induced by exercise on neurotrophins and brain oxidative metabolism. The objective of this study was to investigate the effects of intense physical training on brain-derived neurotrophic factor (BDNF) levels, COX activity, and lipoperoxidation levels in mice brain cortex. Twenty-seven adult male CF1 mice were assigned to three groups: control untrained, intermittent treadmill exercise (3 × 15 min/day) and continuous treadmill exercise (45 min/day). Training significantly (P < 0.05) increased citrate synthase activity when compared to untrained control. Blood lactate levels classified the exercise as high intensity. The intermittent training significantly (P < 0.05) reduced in 6.5% the brain cortex COX activity when compared to the control group. BDNF levels significantly (P < 0.05) decreased in both exercise groups. Besides, continuous and intermittent exercise groups significantly (P < 0.05) increased thiobarbituric acid reactive species levels in the brain cortex. In summary, intense exercise promoted brain mitochondrial dysfunction due to decreased BDNF levels in the frontal cortex of mice.     

Effect of long-term swimming exercise on zinc,magnesium, and copper distribution in aged rats

Trace element content of different tissues might be altered by both age and exercise training. We aimed to determine the effects of a 1-yr swimming protocol (60 min/d, 5 day/wk) on tissue levels and the distribution of zinc (Zn), magnesium (Mg), and copper (Cu) in aging rats. Three groups were formed: sedentary and trained old groups and a young control group. Tissue Zn, Mg, and Cu concentrations were measured in the kidney, heart, liver, lungs, and gastrocnemius and soleus muscles. Kidney zinc concentration significantly decreased in the sedentary old group compared to the young control group (p<0.01) and was significantly higher in the trained old group compared to the sedentary old group (p<0.01), whereas Zn levels in the soleus muscle significantly increased in the sedentary old group in comparison to young controls (p<0.05). Tissue Mg concentrations remained unchanged. The sedentary old group exhibited a significant decrease in kidney Cu concentration compared to the young control group (p<0.01). Although kidney Cu levels also decreased in trained old rats in comparison to young controls (p<0.05), they were significantly higher than in sedentary old rats (p<0.01). The decrease in kidney Zn and Cu content as a result of aging was partly prevented by long-term swimming exercise.     

Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver

Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.     

Hypoglycemic Activity of <Emphasis Type="Italic">Grifola frondosa</Emphasis> Rich in Vanadium

The hypoglycemic activity of fermented mushroom of Grifola frondosa rich in vanadium (GFRV) was studied in this paper. Alloxan- and adrenalin-induced hyperglycemic mice were used in the study. The blood glucose and the HbA1c of the mice were analyzed respectively. After the mice were administered (ig) with GFRV, the blood glucose and the HbA1c of alloxan-induced hyperglycemic mice decreased (p < 0.05, p < 0.01) and ascension of blood glucose induced by adrenalin was inhibited (p < 0.01). Also, the bodyweight of the alloxan-induced hyperglycemic mice was increased gradually. In the fermented mushroom of G. frondosa, vanadium at lower doses in combination with G. frondosa induced significant decreases of the blood glucose and HbA1c levels in hyperglycemic mice.     

Protective effects of sulforaphane and aerobic exercise on acute alcoholic hepatic injury in mice

ObjectiveThe paper intends to study the protective effects of sulforaphane (SF) on acute alcoholic hepatic injury in mice by intragastric administration of SF, aerobic exercise and the approach of SF integrated with aerobic exercise.Methodology60 NIH mice were randomly divided into 6 groups of equal number according to their body weight and were intragastrically administrated with 50% ethanol. The serum and liver indexes of each group of mice were detected, and the liver was stained with oil red O for pathological examination.ResultsCompared with the model group, the serum TG and the ratio of liver to body weight of the model mice that suffered from acute alcoholic hepatic injury could be significantly decreased in the group that practiced aerobic exercise, the group administered with SF, and the group treated with the approach of SF integrated with aerobic exercise (P < 0.05). The contents of TG and MDA in liver could be significantly decreased (P < 0.05) and SOD activity could be significantly increased (P < 0.05) both in the group administered with SF and the group treated with the approach of SF integrated with aerobic exercise. Serum VLDL (P < 0.05) could also be significantly reduced in the group treated with the approach of SF integrated with aerobic exercise.ConclusionBoth SF and aerobic exercise could alleviate alcohol-induced acute alcoholic hepatic injury in mice possibly thanks to the working mechanism related to antioxidant stress that reduced the harm posed by alcohol on hepatic cells. In addition, the protective effect of SF on acute alcoholic hepatic injury in mice was stronger than that of aerobic exercise, while the approach of SF integrated with aerobic exercise had the strongest protective effect on acute alcoholic hepatic injury in mice.     

Comparison of the effects of melatonin and pentoxifylline on carbon tetrachloride-induced liver toxicity in mice

The purpose of the study was to determine whether along and in combination melatonin (MLT) and pentoxlfylline (PTX) exerted beneficial effects on histopathological changes and changes in oxidant and antioxidant systems in liver caused by CCl₄-induced liver toxicity in mice. Mice were randomly divided into six groups: control, olive oil, toxicity, MLT, PTX, PTX+MLT. MLT 10 mg/kg/day, PTX 50 mg/kg/day, and the same individual doses in MLT+PTX combination were given intraperitoneally to mice for 7 day. CCl₄ 0.8 mg/kg/day was administered on the 4th, 5th, and 6th days of therapy in all groups except the control and olive oil groups. In the toxicity group, increased concentrations of malondialdehyde (MDA) and lipid hydroperoxides (LOOH) and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found compared to the control and olive oil groups (p < 0.05). Compared to the toxicity group, both the PTX group and the PTX+MLT group had decreased MDA and LOOH levels, whereas MLT reduced only LOOH levels (p < 0.01). MLT, PTX and MLT+PTX increased the GSH-Px and CAT activities compared to the toxicity group (p < 0.05). MLT increased CAT activity compared to PTX and MLT+PTX (p < 0.05). Superoxide dismutase enzyme activity did not change in any group (p < 0.05). Histopatholically, ballooning, degeneration, apoptosis, and bridging necrosis were seen in the toxicity group. MLT, PTX and MLT+PTX decreased the apoptosis and bridging necrosis (p < 0.01), and PTX and MLT+PTX decreased balloon degeneration compared to the toxicity group (p < 0.01). These results indicate that administration of PTX and MLT alone and in combination before onset of liver toxicity might prevent the oxidative damage by reducing oxidative stress and increasing antioxidant enzyme levels.     

Comparison of Hypoglycemic Activity of Trace Elements Absorbed in Fermented Mushroom of <Emphasis Type="Italic">Coprinus comatus</Emphasis>

The effect of fermented mushroom of Coprinus comatus rich in trace elements, including vanadium, chromium, zinc, magnesium, copper, iron, and nickel, on glycemic metabolism was studied in this paper. Alloxan-induced hyperglycemic mice were used in the study. The blood glucose, glycohemoglobin, and glycogen synthesis of the mice were analyzed, respectively. At the same time, the gluconeogenesis of the normal mice was also determined. After the mice were administered (ig) with C. comatus rich in vanadium (CCRV), the blood glucose and the glycohemoglobin of alloxan-induced hyperglycemic mice decreased (p < 0.05, p < 0.01), glycogen synthesis of alloxan-induced hyperglycemic mice elevated (p < 0.01), the gluconeogenesis of the normal mice was inhibited (p < 0.01), and the sugar tolerance of the normal mice was improved. However, the same result did not occur in other groups. Vanadium at lower doses in combination with C. comatus induced significant effect on glycemic metabolism in mice.     

Conjugated Linoleic Acid (CLA), Body Fat,and Apoptosis*

Objective: The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for ≤2 weeks on body fat, energy expenditure, and feed intake. Research Methods and Procedures: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN‐93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation. Results: Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption. Discussion: These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.     

DNA damage in response to an Ironman triathlon

The major aims of this study were to investigate the effect of an Ironman triathlon on DNA migration in the single cell gel electrophoresis assay, apoptosis and necrosis in the cytokinesis-block micronucleus cytome assay with lymphocytes and on changes of total antioxidant capacity in plasma. Blood samples were taken 2 days (d) before, within 20 min, 1 d, 5 d and 19 d post-race. The level of strand breaks decreased (p<0.05) immediately after the race, then increased (p<0.01) 1 d post-race and declined (p<0.01) until 19 d post-race. Apoptotic and necrotic cells decreased (p<0.01) and the total antioxidant status increased (p<0.01) immediately after the race. The results indicate that ultra-endurance exercise does not cause prolonged DNA damage in well-trained male athletes.     

Effects of zinc deficiency and supplementation on malondialdehyde and glutathione levels in blood and tissues of rats performing swimming exercise

The aim of the study was to investigate the effects of zinc deficiency and supplementation on lipid peroxidation and glutathione levels in blood and in some tissues of rats performing swimming exercise. Forty adult male Sprague-Dawley rats were divided into four groups: group 1, zinc-deficient consisted of swimming rats; group 2 consisted of zinc-supplemented swimming rats; groups 3 and 4 were the swimming and nonswimming controls, respectively. The levels of malondialdehyde and glutathione were measured after 4 wk of zinc-deficient or zinc-supplemented diet and 30 min of swimming exercise daily. The erythrocyte glutathione levels of groups 2 and 4 were significantly higher than those of groups 1 and 3 (p<0.01). The plasma malondialdehyde level of group 1 was significantly higher than all other groups. The glutathione levels in liver, kidney, striated muscle, and testes of group 2 were higher than in the other groups (p<0.01) and higher in kidney and striated muscle of group 3 than in groups 1 and 4 (p<0.01). The tissue malondialdehyde levels of striated muscle, liver, kidney, and testes of group 1 were significantly higher than for all other groups (p<0.01). Our findings suggest that both swimming exercise and zinc deficiency result in an increase of lipid peroxidation in tissues and that zinc supplementation prevents these alterations by the activation of the antioxidant system.     

Influence of Dietary Conjugated Linoleic Acid and Fat Source on Body Fat and Apoptosis in Mice*

Objective: To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)‐induced body fat loss or DNA fragmentation. Research Methods and Procedures: Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. Results: The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA‐fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA‐fed mice did not differ in body fat compared with FO‐fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA‐supplemented mice and was not affected by fat source. Discussion: Reductions in linoleic acid concentration made mice more sensitive to CLA‐induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA‐induced DNA fragmentation.     

Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

Influence of Dietary Copper Proteinate on Performance,Selected Biochemical Parameters,Lipid Peroxidation,Liver, and Egg Copper Content in Laying Hens

This study was performed to determine the effects of copper proteinate on performance, blood chemistry, lipid peroxidation status, and organs as well as copper deposition in the liver and eggs of laying hens. Seventy-two 30-week-old Bovans laying hens were distributed into four groups with three replicates. Animals were fed basal diet containing at least 17% crude protein and 2,800 kcal/kg metabolizable energy supplemented with either 0, 150, 300, or 450 mg/kg copper as copper proteinate. Supplementation of 150 and 300 mg/kg copper increased egg production, whereas 450 mg/kg copper decreased (p < 0.001). Liver copper levels were elevated in 300 and 450 mg/kg copper-supplemented groups (p < 0.001). Egg copper contents increased in all treatment groups (p < 0.01). An increase in glucose (p < 0.001) and decreases in albumin (p < 0.01) and total cholesterol (p < 0.05) levels were determined with 300 and 450 mg/kg copper. Supplementation of 450 mg/kg copper increased alkaline phosphatase and gamma glutamyl transpeptidase activities (p < 0.05), malondialdehyde, and high-density lipoprotein levels (p < 0.01) but decreased alanine aminotransferase and lactate dehydrogenase activities (p < 0.01). No gross and microscopic changes were observed in the liver and kidneys. These results indicated that 150 and 300 mg/kg copper increased egg production without having marked adverse effects, but 450 mg/kg copper altered some blood chemistry variables and reduced egg production in laying hens.     

Erdosteine modulates radiocontrast‐induced hepatotoxicity in rat

It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)‐induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM‐induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH‐Px) values and histological evaluation. Twenty‐one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for 1 day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor‐driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH‐Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media‐induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system. Copyright © 2009 John Wiley & Sons, Ltd.     

Cathepsin B inactivation attenuates the apoptotic injury induced by ischemia/reperfusion of mouse liver

Background: A major mechanism underlying warm ischemia/reperfusion (I/R) injury during liver transplantation is the activation of the caspase chain, which leads to apoptosis. Recently, it was demonstrated that the release of cathepsin B, a cysteine protease, from the cytosol in liver injury induces mitochondrial release of cytochrome c and the activation of caspase-3 and -9, thereby leading to apoptosis. The aim of this study was to ascertain if cathepsin B inactivation attenuates the apoptotic injury due to I/R in mouse liver. Methods: A model of segmental (70%) hepatic ischemia was used. Eighteen mice were anesthetized and randomly divided into three groups: (1) Control group: sham operation (laparotomy); (2) Ischemic group: midline laparotomy followed by occlusion of all structures in the portal triad to the left and median lobes for 60 min (ischemic period); (3) Study group: like group 2, but with intraperitoneal administration of a pharmacological inhibitor of cathepsin B (4 mg/100 g) 30 min before induction of ischemia. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. Results: Showed that at 6 h of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with cathepsin B inhibitor (p < 0.05). On fluorometric assay, caspase-3 activity was significantly decreased in group 3 compared to group 2 (p < 0.0001). The reduction in postischemic apoptotic hepatic injury in the cathepsin B inhibitor -treated group was confirmed morphologically, by the significantly fewer apoptotic hepatocyte cells detected (p < 0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (p < 0.05); and by the TUNEL assay (p < 0.05). Conclusion: The administration of cathepsin B inhibitor before induction of ischemia can attenuate postischemic hepatocyte apoptosis and thereby minimize liver damage. Apoptotic hepatic injury seems to be mediated through caspase-3 activity. These findings have important implications for the potential use of cathepsin B inhibitors in I/R injury during liver transplantation.     

Effect of sodium selenosulfate on restoring activities of selenium-dependent enzymes and selenium retention compared with sodium selenite in vitro and in vivo

Sodium selenosulfate has been extensively used as a precursor of selenide ions in the preparation of nano Se-containing compounds. Its biological properties remain completely unknown. Sodium selenosulfate and sodium selenite were added to the medium of HepG2 cells and administered intraperitoneally at a dose of 0.1 mg Se/kg body weight to selenium-deficient mice, respectively. Both of the selenium compounds could increase the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) in a dose-dependent manner in cells and efficiently restore selenium retention and activities of GPx and TrxR in mice. All of the variables were in correlation with the Se supply. There was no distinction in elevating activities of GPx and TrxR between selenosulfate and selenite in vitro. After a 2-d supply of selenosulfate, the activity of GPx in the liver was 65% (p < 0.001) and Se accumulations in the liver, kidney and blood were 64%, 86%, and 65%, respectively, of those treated with selenite (allp < 0.01). With the 7-d selenosulfate supplementation, the activity of GPx in the kidney and activities of TrxR in the liver and kidney were 88%, 75%, and 78%, respectively, of those treated with selenite (allp < 0.01); Se retentions in the liver and kidney were 85% and 93%, respectively of those supplemented with selenite (bothp < 0.01). These facts indicated that selenosulfate could be absorbed and utilized in the biological system. No difference in vitro demonstrated that selenosulfate could be absorbed and generate reduced selenide as efficiently as selenite. The differences between the two compounds in vivo were the result of other factors that affected selenosulfate utilization in tissues.     

SHBG,plasma, and urinary androgens in weight lifters after a strength training

Previous studies with different results have suggested that total and bioavailable testosterone levels are modified by physical exercise. Such changes may be related to modifications in cortisol levels and could be reflected in some urine androgens. To determine how weight lifting training may affect serum and urinary androgens, we measured total serum testosterone (T), cortisol, sex hormone binding globulin (SHBG) and urinary testosterone, epitestosterone, androsterone, and etiocholanolone, in a group of 19 elite weight lifters after 20 weeks of training. SHBG increased (from 27.5 ± 9.5 to 34.7 ± 8.1 nM, p < 0.05) whereas T/SHBG decreased significantly (from 1.10 ± 0.4 to 0.85 ± 0.3, p < 0.05). Serum total testosterone and cortisol did not change significantly. In urine, androsterone and etiocholanolone decreased significantly, whereas testosterone and epitestosterone remained unchanged. Changes in T/SHBG were related positively with changes in urinary androgens (r = 0.680, p < 0.01), and changes in SHBG were negatively related with changes in urinary androgens (r = −0.578, p < 0.01). These results suggest that intense physical activity may have an influence on the elimination of androgenic hormones due mainly to changes in their transporting protein SHBG.     

Skeletal muscle post-conditioning by diazoxide, anti-oxidative and anti-apoptotic mechanisms

Pretreatment with diazoxide, K_ATP channel opener, increases tissue tolerance against ischemia reperfusion (IR) injury. In clinical settings pretreatment is rarely an option therefore we evaluated the effect of post-ischemic treatment with diazoxide on skeletal muscle IR injury. Rats were treated with either saline, diazoxide (K_ATP opener; 40?mg/kg) or 5-hydroxydecanoate (5-HD; mitochondrial K_ATP inhibitor; 40?mg/kg) after skeletal muscle ischemia (3?h) and reperfusion (6, 24 or 48?h). Tissue contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl-2 protein expression and muscle histology were determined. Apoptosis was examined (24 and 48?h) after ischemia. IR induced severe histological damage, increased MDA content and Bax expression (24 and 48?h; p?<?0.01) and decreased CAT and SOD activities (6 and 24?h, p?<?0.01 and 48?h, p?<?0.05), with no significant effect on Bcl-2 expression. Diazoxide reversed IR effects on MDA (6 and 24?h; p?<?0.05), SOD (6 and 24?h; p?<?0.01) and CAT (6 and 48?h, p?<?0.05 and 24?h p?<?0.01) and tissue damage. Diazoxide also decreased Bax (24 and 48?h; p?<?0.05) and increased Bcl-2 protein expression (24 and 48?h; p?<?0.01). Post-ischemic treatment with 5-HD had no significant effect on IR injury. Number of apoptotic nuclei in IR and 5-HD treated groups significantly increased (p?<?0.001) while diazoxide decreased apoptosis (p?<?0.01). The results suggested that post-ischemic treatment with diazoxide decrease oxidative stress in acute phase which modulates expression of apoptotic proteins in the late phase of reperfusion injury. Involvement of KATP channels in this effect require further evaluations.     

Evaluation of the effects of cadmium on rat liver

Abstact Cadmium is one of the most toxic pollutants in environment. Cadmium accumulation in blood affects the renal cortex and causes renal failure. In this study, we aimed to evaluate the effects of cadmium on rat liver tissue. Eighteen male albino rats aged ten weeks old were used in the study. 15 ppm of cadmium was administered to rats via consumption water daily. At the end of the 30th study day, the animals were killed under ether anesthesia. After the liver tissue samples were taken, histopathological and biochemical examinations were performed. Histopathologic changes have included vacuolar and granular degenerations in hepatocytes, heterochromatic nucleuses and sinusoidal and portal widenings. Central vein diameters were normal in cadmium exposed group. Whereas, there was statistically significant difference between two groups by means of sinusoidal (p< 0.001) and portal triad diameters (p< 0.01). Malondialdehyde (MDA) is an indicator of lipid peroxidation. In this study, MDA was used as a marker of oxidative stress-induced liver impairment in cadmium exposed rats. Superoxide dismutase (SOD) and catalase (CAT) activities were also measured to evaluate the changes in antioxidative system in liver tissues. Current findings showed that MDA levels were increased and SOD and CAT activities were decreased in cadmium exposed group compared to control group. The difference between two groups was statistically significant (pvalues: MDA,p< 0.01; CAT,p< 0.01 and SOD,p< 0.05). In conclusion, these findings suggest the role of oxidative mechanisms in cadmium-induced liver tissue damage     

Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1‐Generation Mice

Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in the F₁ generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of male offspring decreased significantly in dose‐related manners on postnatal days (PNDs) 0, 4, 7, and 14 (p = 0.0019, 0.0096, 0.033, and 0.038, respectively) during the lactation period. In female offspring, the average body weights decreased in dose‐related manners on PNDs 0, 4, 7, and 14 (p = 0.0027, 0.0104, 0.0193, and 0.0062, respectively). The survival of dams slightly decreased (p = 0.0209) in the high‐dose group during the lactation period. With respect to behavioral developmental parameters, surface righting on PND 7 of male and female offspring was delayed significantly in a dose‐related manner (p < 0.001 in each). Swimming direction on PND 7 of male offspring was delayed significantly in a dose‐related manner (p < 0.01), and for female offspring it was delayed significantly in the high‐dose group (p < 0.05). Swimming head angle on PND 7 of male offspring was delayed significantly in a dose‐related manner (p < 0.05). Spontaneous behavior examination in males indicated that rearing increased in the high‐dose group in the F₁ generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice