Search

Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined ex vivo using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually. [ABSTRACT FROM AUTHOR]

Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration. [ABSTRACT FROM AUTHOR]

Background/Aim. Recently, there has been an increased interest in novel dietary antioxidants, including omega-3 fatty acids and bioactive proteins present in milk. The aim of this study was to examine potential antioxidant effects of four-weeks long fish-based and milk-based diets in female Wistar rats. Methods. Four-months old rats were divided into three groups receiving either: control diet, diet enriched with fish meal, or diet enriched with milk. The activities of antioxidant enzymes: glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and concentration of thiobarbituric acid reactive substances (TBARS) were determined in liver homogenates obtained at the end of the treatment period. Results. Statistically significant higher activities of GPx (3.52 ± 0.73 U/mg) and CAT (147.25 ± 15.93 U/mg) were detected in rats fed with fishbased meal in comparison with both the control (GPx: 1.93 ± 0.11 U/mg; CAT: 99.37 ± 10.03 U/mg) and the group fed with milk-based diet (GPx: 1.72 ± 0.52 U/mg; CAT: 104.18 ± 37.49 U/mg). Despite somewhat lower concentration of TBARS in the milk-treated group (0.88 ± 0.23 nmoL/mg), no significant differences were detected in comparison with other groups (the control group: 1.00 ± 0.08 nmoL/mg; the fish-based diet group: 1.13 ± 0.15 nmoL/mg). Conclusion. Diet enriched with fish could improve one’s oxidative status by enhancing activities of antioxidant enzymes in the liver tissue. On the contrary, we failed to obtain results suggesting that milk could serve as a source of dietary antioxidants. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41030]

MgSO4 is used as a tocolytic agent. It is considered to be a calcium channel antagonist, but a different mechanism of its action might be involved. The aim of this study was to examine the contribution of calcium concentrations and potassium channels in the mechanism of MgSO4-mediated uterine relaxation. Isolated uteri from female Wister rats were treated with increasing MgSO4 concentrations (0.1-30 mM). MgSO4 induced dose-dependent inhibition of spontaneous activity. Addition of Ca2+ (6 mM and 12 mM) stimulated uterine contractile activity and attenuated the inhibitory activity of MgSO4. In order to analyze the role of different subtypes of potassium channels, Ca2+-stimulated uteri were pretreated with glibenclamide (Glib), a selective ATP-sensitive potassium channel inhibitor (KATP), tetraethylammonium (TEA), a non-specific inhibitor of large conductance calcium-activated potassium channels (BKCa), and 4-aminopyridine (4-AP), a voltage-sensitive potassium channel inhibitor (Kv), at concentrations that had no effect per se. Pretreatment with 4-AP had no effect on MgSO4-mediated relaxation of Ca2+-stimulated uteri. The relaxing effect of MgSO4 was potentiated by pretreatment with glibenclamide. Pretreatment with TEA attenuated the MgSO4-mediated decrease in frequency. Our results suggest that MgSO4 acts as a general calcium antagonist that influences Ca2+-mediated potassium channels. Furthermore, it seems that MgSO4 uterine relaxation activity is partially mediated by selective ATP-sensitive potassium channels, suggesting an ATP-dependent role. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173014: Molecular Mechanisms of Redox Signaling in Homeostasis: Adaptation and Pathology]

Our previous results showed that a single oral dose (1 or 20 mg/kg body weight) of the anti-addiction agent ibogaine induced in rats 6 and 24 h after administration glycogenolytic activity in hepatocytes, followed by a mild oxidative stress. In this work, we examined the in vivo effect of the same doses of ibogaine on rat kidney morphology, antioxidant enzyme (superoxide dismutases (SOD1 and 2), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione- S-transferase) activities, and oxidative stress (TBARS) and redox (-SH groups) parameters. The dose of 1 mg/kg ibogaine induced an elevation in SOD1 activity and decreased GR activity after 6 and 24 h. GR activity was decreased at 6 and 24 h after 20 mg/kg ibogaine administration, suggesting changed redox homeostasis. After 24 h, we observed an increase in moderate morphological changes, without changes in urinalyses, indicating that kidney function was not measurably affected. Nevertheless, kidney-function monitoring during and following ibogaine use in human subjects is advisable. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no.173014: Molecular mechanisms of redox signaling in homeostasis, adaptation and pathology]

Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p

In recent years, computed tomography (CT) has become very common in veterinary medicine. It is well known that testicles are organs with high radiosensitivity and their function can be impaired even after exposure to low radiation doses. In this work, we calculated the absorbed radiation doses after CT was performed with different voltage/current levels and correlated it with the activity of antioxidant enzymes in rabbit testicles. Two hours after CT, the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) were increased in the testicles of animals that received an absorbed dose of 29.2 mGy. The same changes, along with elevated glutathione reductase (GR) activity, were observed after 7 days in animals that received the highest absorbed dose (46.3 mGy). It would appear that absorbed doses above 27.8 mGy provoked the antioxidant reaction but the time scale of the reaction was dose-dependent. Examination of the obtained results revealed that the main denominator of CT influence was a higher current. Our results suggest that CT influences the antioxidant status in rabbit testicles. The changes in antioxidant enzyme activities were dose- and time-dependent and influenced by the applied current. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173014: Molecular mechanisms of redox signaling in homeostasis: adaptation and pathology and Grant 175061: Antioxidant protection and potentials for differentiation and regeneration of mesenchymal stem cells from various tissues during the aging process]

The objective of this study was to assess the radiation dose in computed tomography examinations of rabbits using different examination protocols and to correlate these values with the activity of antioxidant enzymes in their red blood cells following irradiation. The presented results revealed that a single, routine computed tomography scan exposure led to a different response of the activity of antioxidant enzymes in red blood cells regarding both dose and time. The results indicate that there is a dose threshold that is about 25 mGy. Doses below that level do not produce any significant changes in the level of antioxidant enzymes activity. On the other hand, the level just above that threshold had a significant impact on the antioxidant defence, but in a relatively short time period (2 hours after exposure), compared to the higher dose that requires a longer adaptive period. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173014: Molecular mechanisms of redox signalling in homeostasis: adaptation and pathology]

In this work we compared the mutated liver copper zinc-containing superoxide dismutase (SOD1) protein G93A of the transgenic rat model of familial amyotrophic lateral sclerosis (FALS), to wild-type (WT) rat SOD1. We examined their enzymatic activities and effects on isometric contractions of uteri of healthy virgin rats. G93A SOD1 showed a slightly higher activity than WT SOD1 and, in contrast to WT SOD1, G93A SOD1 did not induce smooth muscle relaxation. This result indicates that effects on smooth muscles are not related to SOD1 enzyme activity and suggest that heterodimers of G93A SOD1 form an ion-conducting pore that diminishes the relaxatory effects of SOD1. We propose that this type of pathogenic feedback affects neurons in FALS. [Projekat Ministarstva nauke Republike Srbije, br. 173014 i br. 175083]

Background: Mutated copper, zinc-containing superoxide dismutase (SOD1) may self-aggregate, an event that could also be an initial cause of motor neuron malfunction leading to disease onset. The effects of human mutated SOD1 protein from the blood of familial amyotrophic lateral sclerosis (FALS) patients bearing Leu144Phe (L144F) mutation were compared to wild-type (WT) human SOD1 derived from healthy examinees, for enzymatic activity and the effects on isometric contractions of non-vascular smooth muscle. Methods: We isolated WT and L144F SOD1 enzymes from eight patients with FALS, L144F mutation in exon 5 and eight healthy controls. We then investigated SOD1 activities in the obtained samples by the adrenaline method and profiled them electrophoretically. Finally, we applied WT and L144F SOD1 on the isolated rat uterus. Results: L144F SOD1 showed lower superoxide-dismutating activity compared to WT human SOD1. We found that, in contrast to WT human SOD1, mutated L144F does not induce smooth muscle relaxation. Conclusions: Our data suggest that the lack of relaxation of muscle tonus in the presence of mutated SOD1 may have pathogenic feedback effects in FALS.

Controlling the number of ticks as carriers of infectious diseases is very important. The process is sometimes compromised by activating the protective mechanisms of the tick itself. Glutathione-S-transferases activity (GSTs) was the subject of our investigation of tick abundance after pyrethroid treatment. We determined GSTs activity in ticks collected from six locations in Belgrade before and after pyrethroid treatment and correlated it with the number of ticks in the locations. The results showed that tick abundance correlated with GSTs activity. On the other hand, treatment efficiency was location-dependent, being similar in each particular location in both April (spring) and October (autumn). Our results suggest that GSTs activity reflects the influence of both present local allelochemicals from different environmental seasonal vegetation and applied pyrethroid. We can conclude that by evaluating GSTs activity in ticks from particular locations as well as during the treatment with acaricides tick removal practice could be improved. [ABSTRACT FROM AUTHOR]

We tested the relaxant effect of increased protamine sulfate (PS) amounts (10, 20, 50, 100 and 150 μg/ml) on the isolated mesenteric arteries of normotensive and spontaneously hypertensive (SH) rats, with or without endothelium. PS caused concentration-dependent relaxation of isolated mesenteric arteries in both types of rats. The relaxation effect of PS was lower in SH rats than in normotensive ones. Our results indicate that the vascular smooth muscles play a significant role in PS-mediated relaxation.

Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment. [ABSTRACT FROM AUTHOR]

Our previous results showed that a single oral dose (1 or 20 mg/kg body weight) of the anti-addiction agent ibogaine induced in rats 6 and 24 h after administration glycogenolytic activity in hepatocytes, followed by a mild oxidative stress. In this work, we examined the in vivo effect of the same doses of ibogaine on rat kidney morphology, antioxidant enzyme (superoxide dismutases (SOD1 and 2), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione-S-transferase) activities, and oxidative stress (TBARS) and redox (-SH groups) parameters. The dose of 1 mg/kg ibogaine induced an elevation in SOD1 activity and decreased GR activity after 6 and 24 h. GR activity was decreased at 6 and 24 h after 20 mg/kg ibogaine administration, suggesting changed redox homeostasis. After 24 h, we observed an increase in moderate morphological changes, without changes in urinalyses, indicating that kidney function was not measurably affected. Nevertheless, kidney-function monitoring during and following ibogaine use in human subjects is advisable. [ABSTRACT FROM AUTHOR]

Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p<0.01), suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls (p<0.01), suggesting mild oxidative stress. Our results show that ibogaine treatment influenced hepatic redox homeostasis, but not sufficiently to remodel antioxidant enzyme activities at 6 and 24 h post-ibogaine application. [ABSTRACT FROM AUTHOR]

Ibogaine effects are mediated by cellular receptors, ATP depletion followed by ROS production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since the role of KATP channels and β-adrenoceptors in ROS cellular circuit was established here we explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.e., 28.8 μmol/L) was applied to isolated rat uterus (spontaneous and Ca2+-stimulated) and contractility and antioxidant enzymes activity were monitored during 4 h. Ibogaine increased amplitude and frequency of spontaneous active uteri immediately after addition that was prevented by propranolol (β1 and β2 adrenoceptors selective antagonists) and glibenclamide (KATP sensitive channels inhibitor; only frequency) pre-treatment. In Ca2+-stimulated uteri, ibogaine decreased both amplitude and frequency after 4 h. Pre-treatment with propranolol abolished ibogaine induced amplitude lowering, while glibenclamide had no effect. In both types of active uterus, ibogaine induced a decrease in SOD1 and an increase in CAT activity after 2 h. In Ca2+-stimulated uterus, there was also a decrease of SOD2 activity after 2 h. After 4 h, SOD1 activity returned to the baseline level, but GSH-Px activity increased. Pre-treatment with both propranolol and glibenclamide abolished observed changes of antioxidant enzymes activity suggesting that ibogaine pro-antioxidative effectiveness is β-adrenergic receptors and KATP channels mediated. [ABSTRACT FROM AUTHOR]

H2S was shown as an uterine relaxant. However, the signaling pathways, including ion channels regulated by H2S mediating relaxation in uterus are still unknown. The effects on contractility in response to sodium sulphide Na2S were examined on myometrial strips from virgin Wistar rats. Our results showed that Na2S induces concentration-dependent relaxations affecting amplitude as well as frequency of contractions. Activation of potassium channels, and in particular of KATP, was one of the primary mechanisms proposed, responsible for the relaxing effects of H2S. Sodium sulphide (20–200×10−6 M) inhibits myometrial contractility through a K-channel-independent mechanism. An inhibitor of 4,4 – inhibitor of exchanger and/or Cl− channel, DIDS, caused a significant rightward shift of the Na2S concentration–response curve. We performed experiments aimed at different Ca2+ concentrations, using spontaneous, calcium and KCl (15mM and 75mM) induced contractions, as well as pharmacological inhibitors of calcium channels and modulators, showing that Na2S induced relaxation is dependent on the precontractile agent used. Taken together, our results suggests that decreased frequency induced by Na2S could be a consequence of a alterated pacemaker cells which might be related for Ca2+ events originates from sarco endoplasmatic reticulum and/or mitochondria. [ABSTRACT FROM AUTHOR]