Decreased Creatine Kinase Activity Research Articles

Photobiomodulation Therapy Combined with a Static Magnetic Field Applied in Different Moments Enhances Performance and Accelerates Muscle Recovery in CrossFit® Athletes: A Randomized, Triple-Blind, Placebo-Controlled Crossover Trial

The ergogenic effects of photobiomodulation therapy combined with a static magnetic field (PBMT-sMF) on exercises with characteristics similar to those of CrossFit® are unknown. This study was aimed at investigating the effects of PBMT-sMF applied at different times on recovery and physical performance in CrossFit® athletes by analyzing functional aspects, muscle damage, inflammatory processes, and oxidative stress. This was a prospectively registered, triple-blinded, placebo-controlled, crossover trial. CrossFit® athletes were recruited and assigned to receive one of the four possible interventions. Each intervention included protocols before and after the exercise (referred to as the workout of the day (WOD)). The four possibilities of intervention were as follows: placebo before and after WOD (placebo), PBMT-sMF before and placebo after WOD (PBMT-sMF before), placebo before and PBMT-sMF after WOD (PBMT-sMF after), and PBMT-sMF before and after WOD (PBMT-sMF before and after). The order of possibilities for the interventions was randomized. The primary outcome was the functional test performance. The secondary outcomes were the subjective perception of exertion, muscle damage, inflammation, and oxidative stress. The outcomes were measured before the WOD; immediately after the intervention; and 1, 24, and 48 hours after the WOD. Statistical analysis was performed using repeated measures ANOVA followed by the Bonferroni post hoc test to examine the differences between the interventions at each time point. Twelve participants were randomized and analyzed for each sequence. PBMT-sMF enhanced the performance on functional tests (calculated as a percentage of change) when applied before or after WOD in the assessment performed immediately post-WOD and at 24 and 48 hours later (p < 0.05) compared to placebo and PBMT-sMF before and after WOD. In terms of the secondary outcomes, PBMT-sMF applied before or after WOD significantly decreased the creatine kinase, catalase, and superoxide dismutase activities and interleukin-6, thiobarbituric acid, and carbonylated protein levels (all p < 0.05) compared to the other possibilities of intervention. In addition, PBMT-sMF applied before and after WOD decreased creatine kinase activity at 24 hours and IL-6 levels at 24 and 48 hours compared to placebo (p < 0.05). None of the participants reported any adverse events. PBMT-sMF enhanced the performance of functional tests, decreased the levels of biochemical markers of muscle damage and inflammation, decreased oxidative stress, and increased antioxidant activity in CrossFit® athletes when applied before or after WOD.

Comparison of Effect of Piperine and Capsaicin with Tabata Exercise on Changes in Serum Nitric Oxide and Creatine Kinase of Kung Fu Boys

Introduction: Tabata exercise programs can produce free radicals and muscle soreness and herbal supplements may be helpful as mediators in response to oxidative damage and muscle stress. Therefore, the purpose of this study was to compare the effects of these two supplements with Tabata exercise activity on nitric oxide and creatine kinase enzyme. Methods: The research was a quasi-experimental one and the participants were boys practicing Kung Fu. Among them, 33 boys (19-25 years old) were selected as a research sample by obtaining written consent and were randomly divided into three groups: Tabata exercise, Tabata exercise + capsaicin, Tabata exercise + piperine). During the eight weeks of piperine and capsaicin supplementation, all three groups participated in a Tabata training protocol. After the last session, blood sampling was taken in two basic stages immediately.The results were compared with one-way analysis of variance and Bonferroni test in the inferential section and SPSS version 16 software. Results: Creatine kinase activity in the two groups of supplement + exercise compared to the exercise group had a significant decrease (p = 0.004) and nitric oxide (p = 0.001) in the two groups of supplement + exercise compared to the exercise group had a significant increase. These changes were more pronounced in the Tabata exercise group with capsaicin supplementation. This significance was confirmed by Bonferroni test. There was no significant difference between the two groups of Tabata exercise and capsaicin and peprin consumption. Conclusion: Both piperine and capsaicin supplements decreased creatine kinase activity and increased nitric oxide. These two supplements were able to reduce some of the oxidative damage and muscle stress resulting from exercise by different mechanisms.

Acetylation of muscle creatine kinase negatively impacts high-energy phosphotransfer in heart failure.

A hallmark of impaired myocardial energetics in failing hearts is the downregulation of the creatine kinase (CK) system. In heart failure patients and animal models, myocardial phosphocreatine content and the flux of the CK reaction are negatively correlated with the outcome of heart failure. While decreased CK activity is highly reproducible in failing hearts, the underlying mechanisms remains elusive. Here, we report an inverse relationship between the activity and acetylation of CK muscle form (CKM) in human and mouse failing hearts. Hyperacetylation of recombinant CKM disrupted MM homodimer formation and reduced enzymatic activity, which could be reversed by sirtuin 2 treatment. Mass spectrometry analysis identified multiple lysine residues on the MM dimer interface, which were hyperacetylated in the failing hearts. Molecular modeling of CK MM homodimer suggested that hyperacetylation prevented dimer formation through interfering salt bridges within and between the 2 monomers. Deacetylation by sirtuin 2 reduced acetylation of the critical lysine residues, improved dimer formation, and restored CKM activity from failing heart tissue. These findings reveal a potentially novel mechanism in the regulation of CK activity and provide a potential target for improving high-energy phosphoryl transfer in heart failure.

Topical application of (S)-(-)-limonene is as effective as phonophoresis for improving oxidative parameters of injured skeletal muscle in rats.

The aim of this study is to investigate the effects of limonene, alone or associated with therapeutic ultrasound, on oxidative stress following skeletal muscle injury. Thirty male Wistar rats were divided into 5 groups: CTR-control, MI-muscle injury without treatment, TPU-therapeutic pulsed ultrasound alone, TPU + LIM-phonophoresis with 5% limonene, and LIM-5% limonene applied topically. Muscle injury was induced by a mechanical abrupt impact over gastrocnemius muscle. The animals were treated in the following intervals: 2, 12, 24, 48, 72, and 96h after injury. Blood and gastrocnemius samples were collected 98h after lesion for data analysis. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity, lipid peroxidation (TBARS) levels, catalase (CAT), and superoxide dismutase (SOD) activity were assessed. CK (p = 0.01), SOD activity (p < 0.01), and TBARS levels (p < 0.01) were increased after injury. There was no effect on LDH levels in any group. Phonophoresis (TABRS p < 0.01; SOD p = 0.01), TPU alone (TBARS p < 0.01; SOD p = 0.01), and LIM alone (TBARS p < 0.01; SOD p < 0.01) reduced TBARS levels and SOD activity after muscle injury. There was no change for CAT activity after injury. Only phonophoresis reduced CK activity after injury (p < 0.01). There was no difference between phonophoresis, TPU alone and LIM alone groups for TBARS, SOD, CAT, and LDH. Limonene alone and TPU alone were effective in reducing oxidative stress parameters after skeletal muscle injury. Only phonophoresis decreased CK activity. Skeletal muscle injury increases reactive oxidative species (ROS) levels and muscle proteins activity as creatine kinase (CK) and lactate dehydrogenase (LDH). Five percent limonene, alone or associated with therapeutic pulsed ultrasound, exhibited reduction of CK, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation markers (TBARS). Graphical abstract.

Renal Protective Effects of L-Carnitine on Lead-Induced Nephropathy in Wistar Rats

Background: Lead is a heavy metal used in industries in developing countries. Lead exposure remains a widespread problem. Lead may induce molecular damage in the kidney as a consequence of Reactive Oxygen Species (ROS) formation, induction of caspase-3, and apoptosis.Methods: Thirty male Wistar rats (Mean±SD weight: 300±20 g) were randomly divided into 3 equal groups: control (normal saline, oral), lead group (lead 100 mg/kg/d, oral) and lead+L-Carnitine (lead 100 mg/kg+L-Carnitine 200 mg/kg, intraperitoneal injection) for one week. At the end of the experiment, plasma creatine kinase activity, plasma creatinine and urea concentrations and plasma Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), catalase and nitric oxide levels were determined. Glutathione and malondialdehyde levels in renal tissue were also measured.Results: Creatine kinase, creatinine and urea levels increased significantly, in the group treated with lead (P<0.05), compared to the control group. Administration of L-Carnitine in (Lead+carnitine treated group) significantly (P<0.05) decreased creatine kinase activity and plasma urea and creatinine contents. Enzymatic activity (SOD, GPx, and CAT) decreased significantly in the lead group, in comparison with the control group (P<0.05). Treatment with L-Carnitine significantly retrieved the depletion in enzyme activity (P<0.05). However, there were no significant differences in the GPx parameter between the Lead+carnitine group, in comparison with the control group.Conclusion: L-Carnitine administration in rats with lead-induced nephropathy led to improved kidney protection, due to the reduction of Lipid Peroxidation (LPO). Furthermore, L-Carnitine prevents the adverse effects of Reactive Oxygen Species (ROS), which is an important biomolecules mechanism.

Levels of Thyroid Hormones and Indices of Energy Metabolism in the Cerebral Cortex of Rats with Experimental Alzheimer’s Disease

The study was carried out on 30 mature WAG rats, 15 intact control animals and 15 rats with modeled Alzheimer’s disease (AD) induced by course injections of scopolamine (27 days, 1 mg/kg, i.p. daily). The contents of ATP, glucose, pyruvate, and lactate were measured spectrophotometrically in homogenates of the brain cortex of the animals. The levels of TSH, T3, and T4 in blood serum and those of T3 and T4 in cortex homogenates were estimated using ELISA. The activities of pyruvate dehydrogenase, creatine phosphokinase, and key enzymes of the tricarboxylic acid cycle (TCA) were measured in the mitochondria using a spectrophotometric technique. It was found that the content of T3 in the brain cortex of rats was much lower than in the controls against the background of higher T4 concentrations, which was indicative of the development of local hypothyroidism in the brain. The increased activity of pyruvate dehydrogenase against the background of low activities of TCA cycle enzymes in brain homogenates was observed. The decreased creatine kinase activity and low ATP contents were also found. Local hypothyroidism in the brain cortex is believed to be one of the significant factors inducing the development of strong energy deficiency and reducing the activity of Krebs cycle enzymes. Consequently, this contributes to the death of neurons in experimental AD in rats.

Disruption of Energy Transfer and Redox Status by Sulfite in Hippocampus, Striatum, and Cerebellum of Developing Rats.

Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities, whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase (CK) activity, mitochondrial respiration and redox status in hippocampus, striatum and cerebellum of developing rats. Our in vitro results showed that sulfite and thiosulfate decreased CK activity, whereas sulfite also increased malondialdehyde (MDA) levels in all brain structures evaluated. Sulfite further diminished mitochondrial respiration and increased DCFH oxidation and hydrogen peroxide production in hippocampus. Sulfite-induced CK activity decrease was prevented by melatonin (MEL), resveratrol (RSV), and dithiothreitol while increase of MDA levels was prevented by MEL and RSV. Regarding the antioxidant system, sulfite increased glutathione concentrations in hippocampus and striatum. In addition, sulfite decreased the activities of glutathione peroxidase in all brain structures, of glutathione S-transferase in hippocampus and cerebellum, and of glutathione reductase in cerebellum. In vivo experiments performed with intrahippocampal administration of sulfite demonstrated that this metabolite increased superoxide dismutase activity without altering other biochemical parameters in rat hippocampus. Our data suggest that impairment of energy metabolism and redox status may be important pathomechanisms involved in brain damage observed in individuals with SO deficiency.

Neurobehavioral Alterations and Brain Creatine Kinase System Changes in Chronic Renal Failure Induced Male Wistar Rats: Impact of Erythropoietin Supplementation

Chronic renal failure (CRF) is a rapidly growing global health problem and it causes anaemia and cognitive impairment. Recombinant Human erythropoietin (rHu-Epo) has been a promising role in the management of anaemia in CRF subjects and it is well documented. It also shown as a remarkable neuroprotection in both cell cultures and in animal models. Creatine kinase (CK) plays a key role in energy metabolism and its activity found in cytoplasm of several human tissues; major sources of CK include skeletal muscle, myocardium and brain. Studies show brain energy metabolism is key to neuronal cell function and cognitive health. The aim of this study is to investigate the impact of rHu-Epo on CRF induced changes in CK system in serum and brain regions of experimental animals and to test its significance in neurobehavioral changes. Experimental design is divided into two phases to find out the variation between simultaneous and post rHu-Epo Treatment in CRF induced male wistar rats. At the end of 40 days, animals were sacrificed uniformly. In both phases, CK level in serum and selected brain regions such as cerebellum, cerebral cortex and hippocampus were determined by spectrophotometric method and hematological parameters (RBC, Hb, PCV, MCV, MCH, MCHC) were also determined. In results, decreased creatine kinase activity in brain regions and its increased level in serum observed in CRF induced animals. Neurobehavioral changes and alterations in hematological parameters were also seen in CRF induced animals. Supplementation of rHu-Epo in both simultaneous and post treatment group reversed the CRF induced changes including neurobehavioral alterations, significantly. In this study, the protective role of Epo supplementation on CRF induced changes in CK system in both brain and serum and its correlation with neurobehavioral changes were seen along with its antianemic effect.

Effects of Carnitine with and without Glutamine Supplementation on Markers of Muscle Damage and Muscle Soreness among Football Players: A Randomized Controlled Clinical Trial

Background: Exercise-induced muscle damage can affect exercise performance. The purpose of this study is to examine the effects of Carnitine and Glutamine supplementation on markers of muscle damage and muscle soreness after physical exertion on football players.Materials and Methods: Twenty eight healthy male football players aged 21.1±0.7 were recruited in a double blind, randomized, placebo-controlled clinical trial on 3 weeks of supplementation. Before supplementation protocol, each participant had to run on a treadmill for 30 minutes at 75% VO2max. Participants were randomly divided into 4 groups: L-Carnitine, L- Glutamine, L-Carnitine plus L- Glutamine and placebo. Blood samples were obtained pre-exercise and immediately after exercise. Muscle soreness was assessed on both occasions and two days after each exercise.Results: L-Carnitine and L-Glutamine supplementation for 21 days significantly decreased Creatine Kinase activity as a marker of muscle’s damage before (P=0.014) and after exercise (P=0.047), and muscle soreness two days after physical exertion (P=0.057). However, Lactate Dehydrogenase activity was affected by Carnitine supplementation after exercise.Conclusion: Chronic oral supplementation of Carnitine and Glutamine before exercise can reduce chemical markers of muscle tissue damage after exercise. In addition, these supplements may reduce muscle pain after exercise and optimize the processes of muscle tissue repair.[GMJ. 2014;3(4):207-15]

Successful Detection and Removal of a Functional Parathyroid Adenoma in a Pony Using Technetium Tc 99m Sestamibi Scintigraphy

Successful Detection and Removal of a Functional Parathyroid Adenoma in a Pony Using Technetium Tc 99m Sestamibi Scintigraphy

Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid

The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67μmol/g) or saline (11h interval between injections) and 60min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I–III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II–III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.

Evaluation of brain and kidney energy metabolism in an animal model of contrast-induced nephropathy

Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, occurring from 24 to 48 h and up to 5 days after the administration of iodinated contrast media. Encephalopathy may accompany acute renal failure and presents with a complex of symptoms progressing from mild sensorial clouding to delirium and coma. The mechanisms responsible for neurological complications in patients with acute renal failure are still poorly known, but several studies suggest that mitochondrial dysfunction plays a crucial role in the pathogenesis of uremic encephalopathy. Thus, we measured mitochondrial respiratory chain complexes and creatine kinase activities in rat brain and kidney after administration of contrast media. Wistar rats were submitted to 6.0 ml/kg meglumine/sodium diatrizoate administration via the tail vein (acute renal failure induced by contrast media) and saline in an equal volume with the radiocontrast material (control group); 6 days after, the animals were killed and kidney and brain were obtained. The results showed that contrast media administration decreased complexes I and IV activities in cerebral cortex; in prefrontal cortex, complex I activity was inhibited. On the other hand, contrast media administration increased complexes I and II-III activities in hippocampus and striatum and complex IV activity in hippocampus. Moreover, that administration of contrast media also decreased creatine kinase activity in the cerebral cortex. The present findings suggest that the inhibition of mitochondrial respiratory chain complexes and creatine kinase caused by the acute renal failure induced by contrast media administration may be involved in the neurological complications reported in patients and might play a role in the pathogenesis of the encephalopathy caused by acute renal failure.

Brain energy metabolism parameters in an animal model of diabetes

A growing body of evidence has indicated that altered mitochondrial function may be involved in mechanism for the development of diabetic complications. Thus, we investigated whether animal model of diabetes induced by alloxan alters energy metabolism parameters. Wistar rats received one single injection of alloxan (250mg/kg) and after 15days we evaluated mitochondrial respiratory chain complexes I, II, II-III and IV, creatine kinase and citrate synthase activities in prefrontal cortex, hippocampus and striatum. We observed that animal model of diabetes induced by alloxan increased complexes I and IV activities in hippocampus, complexes II and II-III activities in prefrontal cortex and striatum and complex IV in prefrontal cortex; however decreased complex IV activity in striatum. Moreover, diabetes rats decreased creatine kinase activity in striatum and increased citrate synthase activity in hippocampus. In conclusion, this study indicates that the alteration in mitochondrial function is probably involved in the pathophysiology of diabetes.

Effects of N-Acetylcysteine/Deferoxamine, Taurine and RC-3095 on Respiratory Chain Complexes and Creatine Kinase Activities in Rat Brain After Sepsis

The pathogenesis of sepsis is characterized by an overwhelming systemic inflammatory response that can lead to multiple organ failure. Considering that we have recently demonstrated that mitochondrial respiratory chain and creatine kinase (CK) are altered in the brain of rats after cecal ligation and perforation (CLP) and that a combination of N-acetylcysteine/deferoxamine (NAC/DFX), taurine and RC-3095 were shown to be an effective treatment of sepsis, we investigated whether the alterations of these enzymes may be reversed by these drugs. The results demonstrated that CLP inhibited complexes I and II, and that all the treatments were able to reverse this inhibition in all brain areas studied in the present work. On the other hand, complexes III and IV were not affected by sepsis neither by any of the treatments. An increase in CK activity in brain of rats 12 h after CLP was also verified; the administration of NAC/DFX and taurine reversed the increase in CK activity in hippocampus, cerebral cortex, cerebellum and striatum. On the other hand, RC-3095 significantly decreased CK activity, when compared to sham group in all brain areas studied. This is a preliminary study which showed beneficial effects of the treatments we proposed.

Understanding the muscular dystrophy caused by deletion of choline kinase beta in mice

Choline kinase in mice is encoded by two genes, Chka and Chkb. Disruption of murine Chka leads to embryonic lethality, whereas a spontaneously occurring genomic deletion in murine Chkb results in neonatal bone deformity and hindlimb muscular dystrophy. We have investigated the mechanism by which a lack of choline kinase β, encoded by Chkb, causes hindlimb muscular dystrophy. The biosynthesis of phosphatidylcholine (PC) is impaired in the hindlimbs of Chkb −/− mice, with an accumulation of choline and decreased amount of phosphocholine. The activity of CTP:phosphocholine cytidylyltransferase is also decreased in the hindlimb muscle of mutant mice. Concomitantly, the activities of PC phospholipase C and phospholipase A 2 are increased. The mitochondria in Chkb −/− mice are abnormally large and exhibit decreased inner membrane potential. Despite the muscular dystrophy in Chkb −/− mice, we observed increased expression of insulin like growth factor 1 and proliferating cell nuclear antigen. However, regeneration of hindlimb muscles of Chkb −/− mice was impaired when challenged with cardiotoxin. Injection of CDP-choline increased PC content of hindlimb muscle and decreased creatine kinase activity in plasma of Chkb −/− mice. We conclude that the hindlimb muscular dystrophy in Chkb −/− mice is due to attenuated PC biosynthesis and enhanced catabolism of PC.

Brain creatine kinase activity in an animal model of mania

There is evidence pointing to dysfunction at the mitochondrial level as an important target for the understanding of the pathophysiology of bipolar disorder (BD). We assessed creatine kinase (CK) activity in rats submitted to an animal model of mania which included the use of lithium and valproate. In the acute treatment, amphetamine (AMPH) or saline was administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the maintenance treatment, rats were pretreated with lithium, valproate or saline, and between day 8 and 14, AMPH or saline were administered. In both experiments, locomotor activity was assessed by open-field test and CK activity was evaluated in hippocampus, striatum, cerebellum, whole cortex and prefrontal cortex. Our results showed that mood stabilizers reversed AMPH-induced behavioral effects. Moreover, AMPH (acute treatment) inhibited CK activity in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex, and administration of lithium or valproate did not reverse the enzyme inhibition. In the maintenance treatment, AMPH decreased CK activity in saline-pretreated rats in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex. AMPH administration in lithium- or valproate-pretreated animals decreased CK activity in hippocampus, striatum and cortex. Our results showed that AMPH inhibited CK activity and that mood stabilizers were not able to reverse and/or prevent the enzyme inhibition. These findings reinforce the hypothesis that mitochondrial dysfunction plays an important role in the pathophysiology of BD.

Decreased Creatine Kinase Activity Caused by Electroconvulsive Shock

Although several advances have occurred over the past 20 years concerning the use and administration of electroconvulsive therapy to minimize side effects of this treatment, little progress has been made in understanding its mechanism of action. Creatine kinase is a crucial enzyme for brain energy homeostasis, and a decrease of its activity has been associated with neuronal death. This work was performed in order to evaluate creatine kinase activity from rat brain after acute and chronic electroconvulsive shock. Results showed an inhibition of creatine kinase activity in hippocampus, striatum and cortex, after acute and chronic electroconvulsive shock. Our findings demonstrated that creatine kinase activity is altered by electroconvulsive shock.

Inhibition of mitochondrial creatine kinase activity by D-2-hydroxyglutaric acid in cerebellum of young rats.

D-2-Hydroxyglutaric aciduria (DHGA) is a neurometabolic disorder biochemically characterized by tissue accumulation and excretion of high amounts of D-2-hydroxyglutaric acid (DGA). Although the affected patients have predominantly severe neurological findings, the underlying mechanisms of brain injury are virtually unknown. In previous studies we have demonstrated that DGA, at concentrations as low as 0.25 mM, significantly decreased creatine kinase activity and other parameters of energy metabolism in cerebral cortex of young rats. In the present study, we investigated the effect of DGA (0.25-5 mM) on total creatine kinase (tCK) activity, as well as on CK activity in cytosolic (Cy-CK) and mitochondrial (Mi-CK) preparations from cerebellum of 30-day-old Wistar rats in order to test whether the inhibitory effect of DGA on CK was tissue specific. We verified that tCK (22% inhibition) and Mi-CK (40% inhibition) activities were moderately inhibited by DGA at concentrations of 2.5 mM and higher, in contrast to Cy-CK, which was not affected by the acid. Kinetic studies revealed that the inhibitory effect of DGA was noncompetitive in relation to phosphocreatine. We also observed that this inhibition was fully prevented by preincubation of the homogenates with reduced glutathione, suggesting that the inhibition of CK activity by DGA is possibly mediated by modification of essential thiol groups of the enzyme. Our present results therefore demonstrate a relatively weak inhibitory effect of DGA on cerebellum Mi-CK activity, as compared to that provoked in cerebral cortex, and may possibly be related to the neuropathology of DHGA, characterized by cerebral cortex abnormalities.

Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol — induced seizures

The aim of our study was to investigate amino acid and energy metabolism of pentylenetetrazol (PTZ)-kindled animals. Glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, γ-glutamyltransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined in the frontal cortex, cerebellum, hippocampus and pons-medulla regions of Hannover–Wistar rats. The rats were randomly divided into four experimental groups: (a) control; (b) rats which received a single PTZ injection in a subconvulsive dose of 40 mg/kg i.p.; (c) rats which received a single PTZ injection in a convulsive dose of 50 mg/kg i.p.; and (d) PTZ-kindled rats. Kindling increased ALP activity throughout the brain, elevated AST as well as LDH activity in the frontal cortex and hippocampus and decreased CK activity in the frontal cortex and cerebellum. Acute seizures of the same intensity did not induce these alterations. The observed effects therefore are obviously linked to the kindling phenomenon and not to seizure activity. Changes appeared mainly in the frontal cortex and hippocampus, i.e. brain areas believed to be directly involved in kindling.

Effects of free radicals on cytosolic creatine kinase activities and protection by antioxidant enzymes and sulfhydryl compounds.

The main purpose of this study was to investigate the effect of free radicals and experimental diabetes on cytosolic creatine kinase activity in rat heart, muscle and brain. Hydrogen peroxide decreased creatine kinase activity in a dose dependent manner which was reversed by catalase. Xanthine/xanthine oxidase, which produces superoxide anion, lowered the creatine kinase activity in the same manner whose effect was protected by superoxide dismutase. N-acetylcysteine and dithiothreitol also significantly ameliorated the effect of Xanthine/xanthine oxidase and hydrogen peroxide. Experimental diabetes of twenty-one days (induced by alloxan), also caused a similar decrease in the activity of creatine kinase. This led us to the conclusion that the decrease in creatine kinase activity during diabetes could be due to the production of reactive oxygen species. The free radical effect could be on the sulfhydryl groups of the enzyme at the active sites, since addition of sulfhydryl groups like N-acetylcysteine and dithiothreitol showed a significant reversal effect.