Effect of physical exercise on changes in activities of creatine kinase, cytochrome c oxidase and ATP levels caused by ovariectomy.

The reduction in the secretion of ovarian hormones, principally estrogen, is a consequence of menopause. Estrogens act primarily as female sex hormones, but also exert effects on different physiological systems including the central nervous system. The treatment normally used to reduce the symptoms of menopause is the hormone therapy, which seems to be effective in treating symptoms, but it may be responsible for adverse effects. Based on this, there is an increasing demand for alternative therapies that minimize signs and symptoms of menopause. In the present study we investigated the effect of ovariectomy and/or physical exercise on the activities of energy metabolism enzymes, such as creatine kinase (cytosolic and mitochondrial fractions), pyruvate kinase, succinate dehydrogenase, complex II, cytochrome c oxidase, as well as on ATP levels in the hippocampus of adult rats. Adult female Wistar rats with 90 days of age were subjected to ovariectomy (an animal model widely used to mimic the postmenopausal changes). Thirty days after the procedure, the rats were submitted to the exercise protocol, which was performed three times a week for 30 days. Twelve hours after the last training session, the rats were decapitated for subsequent biochemical analyzes. Results showed that ovariectomy did not affect the activities of pyruvate kinase, succinate dehydrogenase and complex II, but decreased the activities of creatine kinase (cytosolic and mitochondrial fractions) and cytochrome c oxidase. ATP levels were also reduced. Exercise did not produce the expected results since it was only able to partially reverse the activity of creatine kinase cytosolic fraction. The results of this study suggest that estrogen deficiency, which occurs as a result of ovariectomy, affects generation systems and energy homeostasis, reducing ATP levels in hippocampus of adult female rats.

Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector?

Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

Toxicological evaluation of chronic exposure to the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one in male rats.

The aim of this study was to evaluate the effect of chronic treatment with the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some behavioral and biochemical parameters in the brain, liver, kidney and serum of 90-day-old male Wistar rats. The animals received the organoselenium at doses of 125, 250 or 500 µg/kg body weight intraperitoneally once daily for 30 days. Results showed that chronic treatment with this compound induced behavioral changes in animals, such as increasing of rearing at dose of 250 µg/kg and increasing of ambulation in all concentrations tested. On the other hand, we did not observe any alterations in the body weight gain of the animals. Moreover, the activity of the enzyme creatine kinase (CK) decreased in the cerebral cortex, cerebellum and kidney and increased in the liver after the chronic treatment with the organoselenium compound at dose of 500 µg/kg. The compound also increased aspartate aminotransferase (AST) and urea levels in serum of rats at 500 µg/kg. Glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were not changed by the treatment. Our results thus show that chronic administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one is able to significantly change the activity of CK in Wistar rats, resulting in a change in cellular energy homeostasis in these tissues, liver damage and behavioral changes in the animals studied.

Effect of chronic administration of the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on oxidative stress in different brain areas of rats.

Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 µg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.