Circadian variations in the activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in the liver of control and streptozotocin-induced diabetic rats

The aim of this study was to examine: the 24 h variation of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase activities, key enzymes for the maintenance of intracellular NADPH concentration, in rat liver in control and streptozotocin-induced diabetic animals. Adult male rats were fed ad libitum and synchronized on a 12:12 h light-dark cycle (lights on 08:00 h). One group of animals was treated with streptozotocin (STZ, 55 mg/kg, intraperitoneal) to induce experimental diabetes. Eight weeks after STZ injection, the animals were sacrificed at six different times of day—1, 5, 9, 13, 17 and 21 Hours After Lights On (HALO)—and livers were obtained. Enzyme activities were determined spectrophotometrically in triplicate in liver homogenates and expressed as units per mg protein. 6-phosphogluconate dehydrogenase activity was measured by substituting 6-phosphogluconate as substrate. Glucose-6-phosphate dehydrogenase activity was determined by monitoring NADPH production. Treatment, circadian time, and interaction between treatment and circadian time factors were tested by either one or two way analysis of variance (ANOVA). Two-way ANOVA revealed that 6-phosphogluconate dehydrogenase activity significantly depended on both the treatment and time of sacrifice. 6-phosphogluconate dehydrogenase activity was higher in control than diabetic animals; whereas, glucose-6-phosphate dehydrogenase activity did not vary over the 24 h in animals made diabetic by STZ treatment. Circadian variation in the activity of 6-phosphogluconate dehydrogenase was also detected in both the control and STZ treatment groups (one-way ANOVA). Time-dependent variation in glucose-6-phosphate dehydrogenase activity during the 24 h was detected in control but not in diabetic rats. No significant interaction was detected between STZ-treatment and time of sacrifice for both hepatic enzyme activities. These results suggest that the activities of NADPH-generating enzymes exhibit 24 h variation, which is not influenced by diabetes.     

Circadian Variations in the Activities of 6‐Phosphogluconate Dehydrogenase and Glucose‐6‐Phosphate Dehydrogenase in the Liver of Conrol and Streptozotocin‐Induced Diabetic Rats

The aim of this study was to examine: the 24 h variation of 6‐phosphogluconate dehydrogenase and glucose‐6‐phosphate dehydrogenase activities, key enzymes for the maintenance of intracellular NADPH concentration, in rat liver in control and streptozotocin‐induced diabetic animals. Adult male rats were fed ad libitum and synchronized on a 12:12 h light‐dark cycle (lights on 08:00 h). One group of animals was treated with streptozotocin (STZ, 55 mg/kg, intraperitoneal) to induce experimental diabetes. Eight weeks after STZ injection, the animals were sacrificed at six different times of day—1, 5, 9, 13, 17 and 21 Hours After Lights On (HALO)—and livers were obtained. Enzyme activities were determined spectrophotometrically in triplicate in liver homogenates and expressed as units per mg protein. 6‐phosphogluconate dehydrogenase activity was measured by substituting 6‐phosphogluconate as substrate. Glucose‐6‐phosphate dehydrogenase activity was determined by monitoring NADPH production. Treatment, circadian time, and interaction between treatment and circadian time factors were tested by either one or two way analysis of variance (ANOVA). Two‐way ANOVA revealed that 6‐phosphogluconate dehydrogenase activity significantly depended on both the treatment and time of sacrifice. 6‐phosphogluconate dehydrogenase activity was higher in control than diabetic animals; whereas, glucose‐6‐phosphate dehydrogenase activity did not vary over the 24 h in animals made diabetic by STZ treatment. Circadian variation in the activity of 6‐phosphogluconate dehydrogenase was also detected in both the control and STZ treatment groups (one‐way ANOVA). Time‐dependent variation in glucose‐6‐phosphate dehydrogenase activity during the 24 h was detected in control but not in diabetic rats. No significant interaction was detected between STZ‐treatment and time of sacrifice for both hepatic enzyme activities. These results suggest that the activities of NADPH‐generating enzymes exhibit 24 h variation, which is not influenced by diabetes.     

Alterations of the plasma selenium concentrations and the activities of tissue peroxide metabolism enzymes in streptozotocin-induced diabetic rats

The activity of aortic glutathione peroxidase, a selenium-dependent enzyme, significantly decreased in rats 4 and 8 months after the injection of streptozotocin (STZ). Catalase activity was shown to occur at low levels in rat aorta and was not influenced by the diabetic state. Superoxide dismutase activity was less than detectable. The activity of selenium-dependent glutathione peroxidase in kidney, but not in lung and liver, increased in diabetic rats. Catalase and superoxide dismutase activities in the kidney were not altered. The plasma lipid peroxide value increased in diabetic rats. The selenium content in plasma of diabetic rats increased markedly while the increase in plasma glutathione peroxidase activities was insignificant. The observed abnormalities in plasma of STZ rats were improved by insulin treatment. The defects in glutathione peroxidase in the diabetic rat aorta were restored by insulin treatment. These results may suggest that the capacity of the antioxidative defense system in the aorta decreased in the diabetic state, and this may help clarify the mechanism of the pathogenesis of endothelial dysfunction associated with diabetes.     

The effect of experimental diabetes on the twenty-four-hour pattern of the vasodilator responses to acetylcholine and isoprenaline in the rat aorta

The aim of this study was to investigate whether time-dependent variations in the relaxant effect of acetylcholine, an endothelium-dependent vasorelaxant via muscarinic receptors, and isoprenaline, a nonselective β-adrenoceptor agonist in rat aorta, are influenced by streptozotocin (STZ)-induced experimental diabetes. Adult male rats were divided randomly into two groups: control and STZ-induced (STZ, 55 mg/kg, intraperitoneal) diabetes. The animals were synchronized to a 12:12 h light-dark cycle (lights on 08:00 h) and sacrificed at six different times of day (1, 5, 9, 13, 17, and 21 hours after lights on; HALO) eight weeks after STZ injection. The in vitro responsiveness of thoracic aorta rings obtained from control and diabetic rats to acetylcholine (10^-9-10^-5 M) and isoprenaline (10^-10-10^-3 M) was determined in six different times. EC₅₀ (the concentration inducing half of the maximum response) values and maximum responses were calculated from cumulative concentration-response curves of the agonists and were analyzed with respect to time and STZ treatment. Treatment, time, and interactions between treatment and time were tested by two-way analysis of variance (ANOVA). To analyze differences due to biological time, one-way ANOVA was used. STZ treatment did not significantly change EC₅₀ values or maximum responses for both agonists. There were statistically significant time-dependent variations in the EC₅₀ values for isoprenaline and maximum responses for both acetylcholine and isoprenaline in control groups by one-way ANOVA, but significant time-dependent variations disappeared in the aortas isolated from STZ-induced diabetic rats. The vasodilator responses to acetylcholine and isoprenaline failed to show any significant interaction (treatment×time of study) between STZ treatment and time of sacrifice in both EC₅₀ values and maximum responses by two-way ANOVA. These results indicate there is a basic temporal pattern in the responses to acetylcholine and isoprenaline in rat aorta which continues in diabetes. It is shown for the first time that experimental diabetes does not change the 24 h pattern of responses to acetylcholine and isoprenaline, and that time-dependent variations in the responses to these agonists disappear in diabetic animals. Although further studies are required to define the underlying mechanism(s) of these findings, results suggest that experimental diabetes can modify the time-dependent vasorelaxant responses of rat aorta. This may help to understand the circadian rhythms in cardiovascular physiology and pathology or in drug effects in diabetes.     

The Effect of Experimental Diabetes on the Twenty‐Four‐Hour Pattern of the Vasodilator Responses to Acetylcholine and Isoprenaline ın the Rat Aorta

The aim of this study was to investigate whether time‐dependent variations in the relaxant effect of acetylcholine, an endothelium‐dependent vasorelaxant via muscarinic receptors, and isoprenaline, a nonselective β‐adrenoceptor agonist in rat aorta, are influenced by streptozotocin (STZ)‐induced experimental diabetes. Adult male rats were divided randomly into two groups: control and STZ‐induced (STZ, 55 mg/kg, intraperitoneal) diabetes. The animals were synchronized to a 12∶12 h light‐dark cycle (lights on 08∶00 h) and sacrificed at six different times of day (1, 5, 9, 13, 17, and 21 hours after lights on; HALO) eight weeks after STZ injection. The in vitro responsiveness of thoracic aorta rings obtained from control and diabetic rats to acetylcholine (10^?9–10^?5 M) and isoprenaline (10^?10–10^?3 M) was determined in six different times. EC₅₀ (the concentration inducing half of the maximum response) values and maximum responses were calculated from cumulative concentration‐response curves of the agonists and were analyzed with respect to time and STZ treatment. Treatment, time, and interactions between treatment and time were tested by two‐way analysis of variance (ANOVA). To analyze differences due to biological time, one‐way ANOVA was used. STZ treatment did not significantly change EC₅₀ values or maximum responses for both agonists. There were statistically significant time‐dependent variations in the EC₅₀ values for isoprenaline and maximum responses for both acetylcholine and isoprenaline in control groups by one‐way ANOVA, but significant time‐dependent variations disappeared in the aortas isolated from STZ‐induced diabetic rats. The vasodilator responses to acetylcholine and isoprenaline failed to show any significant interaction (treatment×time of study) between STZ treatment and time of sacrifice in both EC₅₀ values and maximum responses by two‐way ANOVA. These results indicate there is a basic temporal pattern in the responses to acetylcholine and isoprenaline in rat aorta which continues in diabetes. It is shown for the first time that experimental diabetes does not change the 24 h pattern of responses to acetylcholine and isoprenaline, and that time‐dependent variations in the responses to these agonists disappear in diabetic animals. Although further studies are required to define the underlying mechanism(s) of these findings, results suggest that experimental diabetes can modify the time‐dependent vasorelaxant responses of rat aorta. This may help to understand the circadian rhythms in cardiovascular physiology and pathology or in drug effects in diabetes.     

Protective effect of quercetin in ecto-enzymes,cholinesterases, and myeloperoxidase activities in the lymphocytes of rats exposed to cadmium

The ex vivo and in vitro effects of quercetin on NTPDase, adenosine deaminase (ADA), and acetycholinesterase (AChE) activities in lymphocytes, as well as the effects of quercetin on butyrylcholinesterase (BChE) activity in serum and myeloperoxidase (MPO) activity in plasma were determined in rats. For the ex vivo experiment, animals were orally exposed to Cadmium (Cd) for 45 days. Animals were divided into eight groups: saline/ethanol, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg, and Cd/Querc 50 mg/kg. The ex vivo data showed an increase in the ATP and ADP hydrolysis and ADA activity in Cd-exposed rats when compared to the control group. The treatment with quercetin 25 and 50 mg/kg prevented this increase in the ATP and ADP hydrolysis, while the treatment with quercetin 5, 25, and 50 mg/kg prevented the increase in the ADA activity. AChE, BChE, and MPO activities ex vivo presented an increase in the Cd-exposed group when compared to the control group, and the treatment with quercetin 5, 25, and 50 mg/kg prevented this increase caused by Cd exposure. The in vitro experiment showed that quercetin 5, 10, 25, or 50 µM decreased the ADA activity proportionally to the increase of the concentrations of quercetin when compared to the control group. Thus, we can suggest that the quercetin is able to modulate NTPDase, ADA, AChE, and MPO activities and contribute to maintain the levels of ATP, adenosine, and acetylcholine normal, respectively, exhibiting potent pro-inflammatory and anti-inflammatory actions.     

Hydrazine stress in the diabetic: ornithine decarboxylase activity

Streptozotocin-induced diabetes of 7 weeks duration increased male Sprague-Dawley rat kidney ornithine decarboxylase activity by 4.8-fold but did not affect the liver enzyme. Hydrazine treatment of 4 hr duration stimulated equally kidney ornithine decarboxylase activities of nondiabetic and diabetic rats. Hydrazine treatment increased liver ornithine decarboxylase activity in the nondiabetic rat but did not increase it in the diabetic rat. Since hydrazine stimulates ornithine decarboxylase activity prior to polyamine and protein syntheses, we speculate that the lack of hydrazine stimulation of ornithine decarboxylase in the diabetic liver may be related in part to the unrestrained gluconeogenesis and depressed Kreb's cycle activity: the latter being required for protein synthesis.     

Adenosine triphosphatase activity of streptozotocin-induced diabetic rat brain microsomes. Effect of vitamin E

Hyperglycemia causes protein glycosylation, oxidation and alterations in enzyme activities, which are the underlying causes of diabetic complications. This study was undertaken to test the role of vitamin E treatment on Ca2+-ATPase activity, protein glycosylation and lipid peroxidation in the brain of streptozotocin (STZ)-induced diabetic rats. Male rats weighing about 250-300 g were rendered diabetic by a single STZ injection of 50 mg/kg via the tail vein. Both the diabetic and non-diabetic rats were fed a vitamin E supplemented diet (500 IU/kg/day). Ca2+-ATPase activity was significantly reduced at week 10 of diabetes compared to the control group (p < 0.05), with 0.225+/-0.021 U/I (mean +/- S.E.M.) in the control group and 0.072 +/- 0.008 U/l (mean +/- S.E.M.) in the diabetic group. Vitamin E treatment prevented the enzyme activity from decreasing. The activities observed were 0.226 +/- 0.020 U/l and 0.172 +/- 0.011 U/I (mean +/- S.E.M.) in the vitamin E-treated control and diabetic group, respectively. STZ-induced diabetes resulted in an increased protein glycosylation and lipid peroxidation. Vitamin E treatment led to a significant inhibition in blood glucose, protein glycosylation and lipid peroxidation, which in turn prevented abnormal activity of the enzyme in the brain. This study indicates that vitamin E supplementation may reduce complications of diabetes in the brain.     

Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity. Several studies suggest that supplementation with an antioxidant can influence cisplatin-induced hepatotoxicity. The present study was designed to determine the effects of cisplatin on the liver oxidant/antioxidant system, and the possible protective effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by cisplatin. Twenty-four adult female Wistar albino rats were divided into four groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin and CAPE were injected intraperitoneally. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the other three groups. XO activity was lower in the cisplatin group than the control group. MPO activity was also increased in the cisplatin group compared to the control and CAPE groups. It can be concluded that CAPE may prevent cisplatin-induced oxidative changes in liver by strengthening the antioxidant defence system by reducing reactive oxygen species and increasing antioxidant enzyme activities.     

Adenosine deaminase: physical and chemical properties of partially purified mitochondrial and cytosol enzyme from rat liver.

Adenosine deaminase (ADA) was partially purified 486- and 994-fold from rat liver mitochondria and cytosol, respectively. Relative molecular mass of the enzymes from both fractions was 34,000. Km for adenosine and 2'-deoxy-adenosine were 3.08 x 10(-5) M and 3.03 x 10(-5) M for mitochondrial ADA and 3.12 x 10(-5) M and 2.87 x 10(-5) M for cytosolic ADA. The enzyme from both subcellular fractions had the maximum activity at pH 7.5-8.0, and pI 5.2 and 4.2 for mitochondrial and cytosolic enzyme, respectively. The enzyme was inhibited by erythro-9-(2-hydroxy-3-nonyl)adenine and 2'-deoxycoformycin with Ki 4.4 x 10(-7) M and 3.2 x 10(-7) M for mitochondrial ADA and 4.9 x 10(-7) M 2.8 x 10(-7) M for cytosolic ADA. Among the natural nucleoside and deoxynucleotide derivatives tested, deoxy-GTP and UTP inhibited only cytosolic adenosine deaminase by 60% and 40%, respectively.     

Protective role of zinc in liver damage in experimental diabetes demonstrated via different biochemical parameters

Diabetes mellitus is a serious worldwide metabolic disease, which is accompanied by hyperglycaemia and affects all organs and body system. Zinc (Zn) is a basic cofactor for many enzymes, which also plays an important role in stabilising the structure of insulin. Liver is the most important target organ after pancreas in diabetic complications. In this study, we aimed to investigate the protective role of Zn in liver damage in streptozotocin (STZ)‐induced diabetes mellitus. There are four experimental groups of female Swiss albino rats: group I: control; group II: control + ZnSO₄; group III: STZ‐induced diabetic animals and group IV: STZ‐diabetic + ZnSO₄. To induce diabetes, STZ was injected intraperitoneally (65 mg/kg). ZnSO₄ (100 mg/kg) was given daily to groups II and IV by gavage for 60 days. At the end of the experiment, rats were killed under anaesthesia and liver tissues were collected. In the diabetic group, hexose, hexosamine, fucose, sialic acid levels, arginase, adenosine deaminase, tissue factor activities and protein carbonyl levels increased, whereas catalase, superoxide dismutase, glutathione‐S‐transferase, glutathione peroxidase, glutathione reductase and Na⁺/K⁺‐ATPase activities decreased. The administration of Zn to the diabetic group reversed all the negative effects/activities. According to these results, we can suggest that Zn has a protective role against STZ‐induced diabetic liver damage.     

Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats

Lipid disorders and increased oxidative stress may exacerbate some complications of diabetes mellitus. Previous studies have implicated the beneficial effects of some antioxidants, omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the protection of cells from the destructive effect of increased lipids and lipid peroxidation products. This study, therefore, was designed to investigate the effects of cod liver oil (CLO, Lysi Ltd. Island), which comprises mainly vitamin A, PUFAs, EPA and DHA. Effects were monitored on plasma lipids, lipid peroxidation products (MDA) and the activities of antioxidant enzymes, glutathione peroxidase (GSHPx) and catalase in heart, liver, kidney and lung of non-diabetic control and streptozotocin (STZ)-induced-diabetic rats. Two days after STZ-injection (55 mg kg(-1) i.p.), non-diabetic control and diabetic rats were divided randomly into two groups as untreated or treated with CLO (0.5 ml kg(-1) rat per day) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic animals; CLO treatment almost completely prevented these abnormalities in triacylglycerol and cholesterol, but hyperglycaemia was partially controlled. CLO also provided better weight gain in diabetic animals. In untreated diabetic rats, MDA markedly increased in aorta, heart and liver but was not significantly changed in kidney and lung. This was accompanied by a significant increase in both GSHPx and catalase enzyme activities in aorta, heart, and liver of diabetic rats. In kidney and lung, diabetes resulted in reduced catalase while GSHPx was significantly activated. In aorta, heart, and liver, diabetes-induced changes in MDA were entirely prevented by CLO treatment. In the tissues of CLO-treated diabetic animals, GSHPx activity paralleled those of control animals. CLO treatment also caused significant improvements in catalase activities in every tissue of diabetic rats, but failed to affect MDA and antioxidant activity in control animals. The current study suggests that the treatment of diabetic rats with CLO provides better control of glucose and lipid metabolism, allows recovery of normal growth rate, prevents oxidative/peroxidative stress and ameliorates endogenous antioxidant enzyme activities in various tissues. Because CLO contains a plethora of beneficial compounds together, its use for the management of diabetes-induced complications may provide important advantages.     

Prior heat stress induces moderation of diabetic alterations in glycogen metabolism of rats

Adaptation to one environmental stressor sometimes provides protection against additional, more intensive type of stress, a phenomenon called cross-tolerance. We aimed to estimate theprotection provided by acute heat stress (AHS) over carbohydrate disturbances in streptozotocin-diabetic rats. We investigated changes in activity of some hepatic glycolitic and gluconeogenic enzymes, and concentration of some substrates in control and diabetic animals exposed to AHS (41±0.5°C / 1 h), with 1 h and 24 h recovery at room temperature before sacrifice or induction of streptozotocin (STZ)-diabetes, respectively. AHS with 1 h-recovery before sacrifice resulted in intensive glycogenolysis, directed to endogenous glucose production and further utilization of glucose by peripheral tissues, while 24 h recovery resulted in a slight tendency towards normalization of metabolic disturbances caused by AHS. Experimental diabetes caused a significant decrease of substrates and glycolytic enzymes, but an increase of gluconeogenic enzymes. In diabetic animals previously exposed to AHS we measured a less intensive decrease of liver glycogen and glucose-6-phosphate concentration and hexokinase activity, as well as less intensive increase of liver glucose concentration, glucose-6-phosphatase and fructose-1,6-bisphosphatase activity compared to control diabetic animals that had been maintained at room temperature. Prior AHS provided some protection over diabetes-induced alterations in carbohydrate-related parameters (see graphical apstract), indicating a possible development of cross-tolerance phenomenon between the two stressors, AHS and STZ-diabetes.     

Postnatal changes in enzyme activities of rat myocardial adenine nucleotide catabolic pathway

Three catabolic enzymes, 5'-nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and one anabolic enzyme, myokinase (MK) involved in adenine nucleotide (AN) metabolism were studied in myocardium from 4 to 105 day old rats. The specific enzyme activities (nmoles/min/mg protein) at day 4 were 35.3 for 5'NT, 28.4 for ADA, 43.3 for PNP, and 5 X 10(3) for MK. At day 7, 5'NT, activities rose to 450%; PNP and ADA 150%; and MK 120%; of the day 4 level. The activities of the three catabolic enzymes were elevated for one or two weeks then declined rapidly. By day 34, they were slightly above the adult values. MK activity displayed a different time course. It continued to increase slowly with age after the initial surge. Compared to the adult heart, the total activities of these catabolic enzymes in the one- to three-week-old heart were 30% to 220% higher. This transient elevation in AN catabolic enzyme activities may be related to active DNA synthesis and cell proliferation occurred in the rat myocardium during the same period.     

Dosage effect of streptozotocin on rat tissue enzyme activities and glycogen concentration

The effect of different dosages of streptozotocin (STZ) on selected rat tissue enzyme activities and glycogen concentration were investigated. The rats were administered STZ intravenously at 60 (STZ-60), 80 (STZ-80), 100 (STZ-100), and 150 (STZ-150) mg/kg body weight. They were used 3 weeks postinjection. Mortality prior to kill occurred only in the STZ-100 and STZ-150 rats. All diabetic rats showed reduced growth rate, hyperglycemia, hypoinsulinemia, and hyperlipemia. Phosphofructokinase (PFK) and succinate dehydrogenase (SDH) activities were significantly reduced in the red gastrocnemius muscle of all diabetic rats, and in the white gastrocnemius and soleus of STZ-100 and STZ-150 groups. PFK activity in the heart remained unaltered, but SDH activity was below normal. Liver SDH activity was not affected by insulin deficiency. Glycogen content was markedly increased in the heart and decreased in the liver of all diabetic rats. Glycogen content in the skeletal muscle was similar to the controls, except for the lower values in the soleus of STZ-100 and STZ-150 rats. When STZ-80 and STZ-150 rats were given insulin therapy, the STZ-80 rats showed a greater response to the treatment. Despite similar levels of plasma immunoreactive insulin among all groups of diabetic rats, the STZ-100 and STZ-150 rats had higher mortality, greater loss in body weight, and alterations in enzyme activities and glycogen content in the tissues studied.     

The effect of benzene on the activity of adenosine deaminase in tissues of rats

Swiss Albino (Rat rattus norvegicus) rats were intraperitoneally injected with a 100 mg kg(-1) dosage of benzene, a toxic and carcinogenic agent widely used for industrial purposes. Changes in the adenosine deaminase (ADA) activity in the liver, kidney and serum of rats were investigated at 0, 2, 4, 8, 16, 32 and 64 h following injection. Serum physiological was administered to each control group. Enzyme activities were measured spectrophotometrically. Our purpose was to further investigations of some diseases caused by benzene, and present evidence of variations in the activity of ADA enzyme effected by benzene. While benzene caused significant inhibitions in ADA activity in the liver at 16 and 32 h and at 0.05 probability level, no significant inhibition or activation occurred at other test periods (hours). ADA activity did not present any significant variation in the kidneys. It was observed that ADA activity displayed similar patterns in the control groups. Comparisons of ADA activities in the two groups showed a statistically significant decrease between 4(th) and 64(th) hours (p< 0.05), demonstrating a direct correlation between benzene and its effects on ADA enzymes.     

Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic,gluconeogenic and lipogenic enzymes

Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADPlinked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4fold higher blood glucose level and a 0.7fold lower body weight compared to normal controls. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities of gluconeogenic enzymes were higher in both liver and kidney during diabetes, however the activities of the lipogenic enzymes were decreased in both tissues during diabetes. Trigonella seed powder treatment to diabetic rats for 21 days brought down the elevated fasting blood glucose levels to control levels. The altered enzyme activities were significantly restored to control values in both the liver and kidney after Trigonella seed powder treatment. The therapeutic role of Trigonella seed powder in type1 diabetes as exemplified in this study can be attributed to the change of glucose and lipid metabolising enzyme activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney. These biochemical effects exerted by Trigonella seeds make it a possible new therapeutic in type1 diabetes.     

Protective effect of atorvastatin on oxidative stress in streptozotocin‐induced diabetic rats independently their lipid‐lowering effects

In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)‐induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high‐density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non‐protein associated sulfhydryl (NP‐SH), total sulfhydryl (T‐SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ‐induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP‐SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ‐induced oxidative damage by reducing TBARS levels and increasing NP‐SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels.     

The influence of a new vanadium compound, bis(2,2'-bipyridine)oxovanadium(IV) sulphate on liver golgi complexes from control and streptozotocin-diabetic rats.

Among the previously studied organic vanadium derivatives showing an anti-diabetic action, we investigated a new complex, bis(2,2'-bipyridine)oxovanadium(IV) sulphate. We tested its ability to normalise parameters previously described for streptozotocin (STZ)-diabetes, such as lower yields of Golgi-rich membrane fraction isolation, decreased activity of Golgi membrane marker enzyme - galactosyltransferase (GalT) - and altered morphology of rat liver Golgi complexes. Oral application as a drinking solution of 1.8 mmol bis(2,2'-bipyridine)oxovanadium(IV) (dissolved in 0.09 M NaCl) caused a similar dispersion of GalT activities in both vanadium treated groups, control and diabetic. Very low activities of the enzyme (characteristic for untreated diabetes) we found only in approximately 35 % of the STZ-diabetic rats treated with the new vanadium compound. The morphology of liver Golgi complexes in diabetic rats treated with bis(2,2'-bipyridine)oxovanadium(IV) sulphate was improved, which manifested itself in the reappearance of vacuoles with VLDL and coated and uncoated secretory vesicles. In view of biochemical and morphological parameters of normalised diabetic rat liver Golgi apparatus, the new vanadium complex was more effective than bis(oxalato)oxovanadium(IV) or bis(kojato)oxovanadium(IV), but in our experimental model, the best anti-diabetic, orally applied drug was the bis(maltolato)oxovanadium(IV) previously investigated.     

Effects of resveratrol on nucleotide degrading enzymes in streptozotocin-induced diabetic rats

AimsDiabetes mellitus is associated with platelet alterations that may contribute to the development of cardiovascular complications. The present study investigates the effects of resveratrol (RSV), an important compound with cardioprotective activities, on NTPDase, ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), 5′-nucleotidase and adenosine deaminase (ADA) activities in platelets from streptozotocin (STZ)-induced diabetic rats.Main methodsThe animals were divided into six groups (n = 8): control/saline; control/RSV 10 mg/kg; control/RSV 20 mg/kg; diabetic/saline; diabetic/RSV 10 mg/kg; diabetic/RSV 20 mg/kg. RSV was administered during 30 days and after this period the blood was collected for enzymatic assay.Key findingsThe results demonstrated that NTPDase, E-NPP and 5′-nucleotidase activities were significantly higher in the diabetic/saline group (P < 0.05) compared to control/saline group. Treatment with RSV significantly increased NTPDase, 5′-nucleotidase and E-NPP activities in the diabetic/RSV10 and diabetic/RSV20 groups (P < 0.05) compared to diabetic/saline group. When RSV was administered per se there was also an increase in the activities of these enzymes in the control/RSV10 and control/RSV20 groups (P < 0.05) compared to control/saline group. ADA activity was significantly increased in the diabetic/saline group (P < 0.05) compared to control/saline group. The treatment with RSV prevented this increase in the diabetic/RSV10 and diabetic/RSV20 groups. No significant differences in ADA activity were observed in the control/RSV10 and control/RSV20 compared to control/saline group.SignificanceThe present findings demonstrate alterations in nucleotide hydrolysis in platelets of STZ-induced diabetic rats and treatment with RSV was able to modulate adenine nucleotide hydrolysis, which may be important in the control of the platelet coagulant status in diabetes.