Necrosis of the spleen resulting from previous storage of the substance within the cells was produced by intravenous injections of 500 mg and 800 mg, respectively, of ethylpalmitate in 30 male Wistar [VELAZ] rats weighting, on average, 200 g. A certain inhomogeneity of the results indicates differences in tissue susceptibility obviously related to the actual functinal state at the spleen. Ethylpalmitate storage was observed to a lesser degree in the Kupffer cells of the liver and in the cells of pulmonary alveoli and septa. This, however, was unassociated with marked necrosis. Other organs [lymph nodes, bone marrow, thymus, kidney, myocardium] did not display significant changes.
- MeSH
- Injections, Intravenous MeSH
- Rats MeSH
- Kupffer Cells MeSH
- Palmitic Acids pharmacology MeSH
- Palmitates administration & dosage pharmacology MeSH
- Spleen drug effects ultrastructure MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- English Abstract MeSH
- Journal Article MeSH
- Names of Substances
- Palmitic Acids MeSH
- Palmitates MeSH
Pesticides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to public and environmental health. The aim of the present study was to investigate the genotoxic potential of a commercial formulation of the fungicide mancozeb by the micronucleus test in bone marrow and the comet assay in total blood of Wistar rats. Adult male Wistar rats were treated with a solution of mancozeb at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days, and compared to a control group. The results indicate that mancozeb induced significantly higher DNA damage as detected by the comet assay and increased the frequency of micronuclei. The results show that mancozeb is genotoxic and may adversely affect the DNA integrity of exposed organisms.
- MeSH
- Ditiocarb toxicity MeSH
- Erythrocytes drug effects metabolism MeSH
- Maneb toxicity MeSH
- Micronucleus Tests MeSH
- Micronuclei, Chromosome-Defective drug effects MeSH
- Erythrocyte Count MeSH
- DNA Damage * MeSH
- Rats, Wistar MeSH
- Zineb toxicity MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Ditiocarb MeSH
- mancozeb MeSH Browser
- Maneb MeSH
- Zineb MeSH
The circadian rhythm of ventricular fibrillation threshold (VFT) and its relation to the heart rate (HR) and the rectal temperature (RT) was studied in female Wistar rats. The animals were exposed to daily light-dark cycles of 12 h of light alternating with 12 h of darkness and were under pentobarbital anaesthesia (40 mg/kg i.p.). The experiments were performed on open chest animals and VFT was measured by direct stimulation of the myocardium. VFT in female rats showed a circadian rhythm with the acrophase -338 degrees (at 22.53 h), with the mesor 2.58 mA and the amplitude 0.33 mA. HR was not significantly changed during the experiments and no dependence was found between VFT and HR during the whole 24-hour period (r = 0.08). The acrophase of the circadian rhythm of HR (on -47 degrees, i.e. at 03.08 h) was shifted to the acrophase of VFT. The circadian rhythms of RT before the application of the anaesthetic agent and under general anaesthesia before the operative interventions had a very similar course with the nearly corresponding acrophases as the circadian rhythm of VFT. It is concluded that the electrical stability of the rat heart measured by VFT shows the significant circadian rhythm in a parallel with the circadian rhythm of RT and probably without dependence on the changes of HR.
- MeSH
- Circadian Rhythm physiology MeSH
- Electric Stimulation MeSH
- Electrophysiology MeSH
- Ventricular Fibrillation physiopathology MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Heart physiology MeSH
- Heart Rate physiology MeSH
- Body Temperature drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm than ketamine, however a number of deaths have been reported. Currently very little is known about the psychopharmacological effects of this compound or its toxicity; therefore we tested, in Wistar rats, the effects of MXE in a series of behavioural tasks, measured its pharmacokinetics and urinary metabolites. Locomotor activity and its spatial characteristics (in the open field) and sensorimotor gating (prepulse inhibition; PPI) were evaluated after 5, 10 and 40mg/kg subcutaneous (sc.) MXE. Pharmacokinetics and brain: serum ratios were evaluated after 10mg/kg sc. MXE so that peak drug concentration data could be used to complement interpretation of maximal behavioural effects. Finally, quantification of metabolites in rat urine collected over 24h was performed after single bolus of MXE 40mg/kg sc. 5 and 10mg/kg MXE induced significant locomotor stimulation, in addition it increased thigmotaxis and decreased time spent in the centre of the open field (indicative of anxiogenesis). By contrast, 40mg/kg reduced locomotion and increased time spent in the centre of the arena, suggesting sedation/anaesthesia or stereotypy. The duration of effects was present for at least 60-90min, although for 5mg/kg, locomotion diminished after 60min. MXE decreased baseline acoustic startle response (ASR) and disrupted PPI, irrespective of testing-onset. MXE (all doses) reduced habituation but only at 60min. Maximal brain levels of MXE were observed 30min after administration, remained high at 60min and progressively declined to around zero after six hours. MXE accumulated in the brain; the brain: serum ratio was between 2.06 and 2.93 throughout the whole observation. The most abundant urinary metabolite was O-desmethylmethoxetamine followed by normethoxetamine. To conclude, MXE acts behaviourally as a typical dissociative anaesthetic with stimulant and anxiogenic effects at lower doses, sedative/anaesthetic effects at higher doses, and as a disruptor of sensorimotor gating. Its duration of action exceeds that of ketamine which is consistent with reports from MXE users. The accumulation of the drug in brain tissue might reflect MXE's stronger potency compared to ketamine and indicate increased toxicity.
- Keywords
- Metabolism, Methoxetamine, Open field, Pharmacokinetics, Prepulse inhibition, Wistar rat,
- MeSH
- Acoustic Stimulation MeSH
- Cyclohexanones metabolism pharmacology MeSH
- Cyclohexylamines metabolism pharmacology MeSH
- Rats MeSH
- Locomotion drug effects MeSH
- Brain drug effects metabolism MeSH
- Exploratory Behavior drug effects MeSH
- Rats, Wistar MeSH
- Prepulse Inhibition drug effects MeSH
- Psychotropic Drugs metabolism pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- 2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone MeSH Browser
- Cyclohexanones MeSH
- Cyclohexylamines MeSH
- Psychotropic Drugs MeSH
- MeSH
- Respiration * MeSH
- Rats physiology MeSH
- Animals, Laboratory physiology MeSH
- Animals MeSH
- Check Tag
- Rats physiology MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory-entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was to investigate naphyrone's pharmacokinetics, acute toxicity, hyperthermic potential and stimulatory and psychotomimetic properties in vivo in male Wistar rats. Pharmacokinetics after 1 mg/kg subcutaneous (sc.) naphyrone were measured over 6 h in serum, the brain, liver and lungs. Rectal temperature (degree Celsius) was measured over 10 h in group-versus individually housed rats after 20 mg/kg sc. In the behavioural experiments, 5, 10 or 20 mg/kg of naphyrone was administered 15 or 60 min prior to testing. Stimulation was assessed in the open field, and sensorimotor processing in a prepulse inhibition (PPI) task. Peak concentrations of naphyrone in serum and tissue were reached at 30 min, with a long-lasting elevation in the brain/serum ratio, consistent with observations of lasting hyperlocomotion in the open field and modest increases in body temperature. Administration of 20 mg/kg transiently enhanced PPI. Naphyrone crosses the blood-brain barrier rapidly and is eliminated slowly, and its long-lasting effects correspond to its pharmacokinetics. No specific signs of acute toxicity were observed; therefore, clinical care and harm-reduction guidance should be in line with that available for other stimulants and cathinones.
- Keywords
- locomotion, naphyrone, novel psychoactive substance, pharmacokinetics, prepulse inhibition, thermoregulation,
- MeSH
- Rats MeSH
- Pentanones pharmacokinetics pharmacology MeSH
- Rats, Wistar MeSH
- Pyrrolidines pharmacokinetics pharmacology MeSH
- Central Nervous System Stimulants pharmacokinetics pharmacology MeSH
- Body Temperature drug effects MeSH
- Body Temperature Regulation drug effects MeSH
- Illicit Drugs pharmacokinetics pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one MeSH Browser
- Pentanones MeSH
- Pyrrolidines MeSH
- Central Nervous System Stimulants MeSH
- Illicit Drugs MeSH
OBJECTIVES: Cyanobacteria are producers of potent and environmentally abundant microcystins, representing an emerging global health issue. In the present study, we investigated the impact of pure microcystins and cyanobacterial biomass on laboratory rats (Wistar albino rats, males, 30 days old) under different exposure scenarios. METHODS: The rats were fed diets containing fish meat with microcystins in various concentrations and forms (cyanobacterial biomass and isolated microcystins) for 28 days. RESULTS: Although considerable amounts of microcystins (MCs) were administered to the rats, all levels of MCs in the liver were close to the detection limit (3-5 ng/g fresh weight) using liquid chromatography - tandem mass spectrometry. Only rats exposed to cyanobacterial biomass had clearly higher hepatic and splenic somatic indexes while markers of oxidative stress (glutathione-S-transferase, glutathione reductase, lipid peroxidatio) were significantly increased in the group exposed to the high dose of MCs. Most of the analysed biochemical parameters did not show clear differences among groups. Levels of bilirubin and lipases were significantly increased only after exposure to cyanobacterial biomass and MCs, respectively. Considering microscopic findings in the liver, kidney, thymus, spleen and brain, histopathology was dominated by alterations in the hepatic parenchyma and renal cortical tubular system. CONCLUSIONS: The present study demonstrates that oral exposure to MCs and cyanobacterial biomass may induce biochemical and detoxification responses associated with damage to liver and kidneys and in the laboratory rat.
- MeSH
- Liver drug effects pathology MeSH
- Carcinogens toxicity MeSH
- Rats MeSH
- Kidney drug effects pathology MeSH
- Microcystins toxicity MeSH
- Rats, Wistar MeSH
- Food Chain MeSH
- Cyanobacteria chemistry MeSH
- Spleen drug effects pathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Carcinogens MeSH
- Microcystins MeSH
Methamphetamine is a psychostimulant drug which causes the release of monoamine neurotransmitters. Although drugs of abuse are known to have analgesic effects, there is a lack of evidence regarding the effect of prenatal exposure to methamphetamine on nociception in adulthood. Adult Wistar rats whose mothers had received daily exposure to methamphetamine (5 mg/kg; s.c.) or saline, during gestation or gestation and lactation periods, were examined for: (1) gender differences in nociception; (2) an association between nociception and gross-motor behavior in the plantar test; (3) effects of cross-fostering on nociception; and (4) analgesic effects of an acute injection of methamphetamine (1 mg/kg s.c.). Nociception was tested using the plantar test on postnatal days 85-90. Prenatal methamphetamine increased sensitivity to pain on forelimbs (p<0.0001) and hind limbs (p<0.05) in females only. Prenatal methamphetamine treated male rats fostered by adoptive injection stressed mothers had higher sensitivity to pain than prenatally injection stressed rats fostered by methamphetamine treated mothers (p<0.05). Acute methamphetamine induced analgesia faster in prenatally methamphetamine exposed rats than in controls. In all groups, analgesia increased in the cranio-caudal direction (p<0.0001). From our behavioral data it can be concluded that exposure to methamphetamine during the prenatal period completely dissociates the relationship between nociception and intensity of overall behavior observed in intact animals in adulthood. Thus, our results indicate that perinatal exposure to psychostimulants may have long-term impact on several functions related to dopaminergic system.
- MeSH
- Behavior, Animal drug effects MeSH
- Estrous Cycle drug effects MeSH
- Rats MeSH
- Maternal Behavior drug effects MeSH
- Pain Measurement MeSH
- Methamphetamine pharmacology MeSH
- Animals, Newborn MeSH
- Pain Perception drug effects MeSH
- Rats, Wistar MeSH
- Central Nervous System Stimulants pharmacology MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Methamphetamine MeSH
- Central Nervous System Stimulants MeSH
OBJECTIVE: In our study we decided to define the harvesting and preservation injury of the graft using Park's scheme for the quantification of morphological changes. ANIMALS: Male Wistar rats (n=25) weighting 322+/-18 g. Harvesting preservation technique: Proximal jejunum (5-7 cm) was flushed with 5 ml of HTK solution and preserved for 0, 1, 6, 9 and 12 hours at 4 degrees C in the same solution. Biopsies for light microscopic evaluations were obtained after the preservation period. Park's scheme was used for the quantitative assessment of histological changes. t-test for two independent samples was used to evaluate statistical significance. HISTOLOGY: The extent of the preservation injury in the samples obtained at 0 hours was of grade 0 and increased to 1.84 after 12 hours of preservation time. At 0 hours of preservation a degree of 0 (s=0: no changes) was observed, after 1 hour, a degree of 0.50 (s=0.47: slight changes, similar to 0 time), after 6 hours a degree of 1 (0.97, s=0.41: discrete subepitelial oedemas in villi apexes), after 9 hours a degree of 2 (1.74, s=0.64: extension of subeppitelial spaces in villi apexes), and after 12 hours a degree of 2 (1.83, s=0.64: more extension of subepitelial spaces) was observed, except for these findings, there were also changes of grade 3 (massive subepitelial edema and sequestration of the mucosa from lamina propria) in the 12-hour group. A statistically significant (p=0.05) difference was found between all groups except for 9 and 12-hour groups. CONCLUSIONS: HISTOLOGY revealed increasing preservation injury with a increasing duration of preservation and its dynamic. (Tab. 1, Fig. 2, Ref: 6.)
- MeSH
- Rats MeSH
- Cold Temperature adverse effects MeSH
- Rats, Wistar MeSH
- Reperfusion Injury pathology MeSH
- Intestinal Mucosa pathology MeSH
- Intestine, Small pathology transplantation MeSH
- Organ Preservation adverse effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND PURPOSE: Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. EXPERIMENTAL APPROACH: Pharmacokinetics, acute effects, and addictive potential in a series of behavioural tests in Wistar rats were performed following subcutaneous (s.c.) administration of DCK (5, 10, and 30 mg·kg-1 ) and its enantiomers S-DCK (10 mg·kg-1 ) and R-DCK (10 mg·kg-1 ). Additionally, activity at human N-methyl-d-aspartate (NMDA) receptors was also evaluated. KEY RESULTS: DCK rapidly crossed the blood brain barrier, with maximum brain levels achieved at 30 min and remaining high at 2 h after administration. Its antagonist activity at NMDA receptors is comparable to that of ketamine with S-DCK being more potent. DCK had stimulatory effects on locomotion, induced place preference, and robustly disrupted PPI. Locomotor stimulant effects tended to disappear more quickly than disruptive effects on PPI. S-DCK had more pronounced stimulatory properties than its R-enantiomer. However, the potency in disrupting PPI was comparable in both enantiomers. CONCLUSION AND IMPLICATIONS: DCK showed similar behavioural and addictive profiles and pharmacodynamics to ketamine, with S-DCK being in general more active. It has a slightly slower pharmacokinetic profile than ketamine, which is consistent with its reported longer duration of action. These findings have implications and significance for understanding the risks associated with illicit use of DCK.
- Keywords
- NMDA receptor, deschloroketamine, enantiomers, locomotion, pharmacokinetics, prepulse inhibition,
- MeSH
- Behavior, Animal * drug effects MeSH
- Ketamine * administration & dosage adverse effects analogs & derivatives pharmacokinetics pharmacology MeSH
- Rats MeSH
- Locomotion * drug effects MeSH
- Rats, Wistar MeSH
- Receptors, N-Methyl-D-Aspartate metabolism MeSH
- Illicit Drugs * adverse effects pharmacokinetics pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ketamine * MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
- Illicit Drugs * MeSH
