Evaluating the effects of rifampin in the prevention of neurogenic symptoms and cardiac arrhythmias caused by the systemic toxicity of lidocaine in rats.

Lidocaine toxicity is caused by unintended intravascular injection or overdose. Lidocaine is metabolized in the liver by the CYP3A4 isoenzyme. The objective was to investigate if the administration of rifampin could accelerate animal recovery and reduce the symptoms of lidocaine toxicity by induction of the CYP3A4. Thirty-six male rats were divided into control and treatment groups, each containing three subgroups. The treatment group received oral rifampin suspension daily for 1 week. In all rats, 2.00% lidocaine was injected intravenously. The first subgroup was monitored for neurological symptoms. In the second subgroup, data were recorded after the electrode was placed in the right hippocampus. Electrocardiograms were taken from the third subgroup. CYP3A4 was measured using an ELISA kit. Neurological recovery was seen after 22 and 15 min in the control and treatment groups, respectively. Rifampin also caused a significant reduction in amplitude and number of field action potentials compared to the control group. Numerous cardiac arrhythmias were observed in the control group. The mean level of CYP3A4 in the treatment group was significantly higher than in the control group. In conclusion, oral rifampin could increase the synthesis of CYP3A4, therefore, the animal recovery from lidocaine toxicity was accelerated.

The link between seizures and prolactin: A study on the effects of anticonvulsant medications on hyperprolactinemia in rats.

Seizures are a common neurological disorder that affects people of all ages. These sudden, uncontrolled electrical disturbances in the brain can cause a variety of symptoms, including convulsions, loss of consciousness, and abnormal sensations. While seizures have long been recognized as a potential cause of hormonal imbalances, recent research has shed new light on the link between seizures and prolactin. The study involved 30 adult female Wistar rats, which were divided into a control group (treated with normal saline) and four treatment groups: chronic group (treated with 30 mg/kg pentylenetetrazol intraperitoneally three days a week for 10 weeks), chronic + Levetiracetam (50 mg/kg, gavage), chronic + Cabergoline (0.05 mg/kg, gavage), and chronic + Levetiracetam (25 mg/kg) + cabergoline (0.025). The drugs were administered three days a week for 10 weeks. Field action potentials were recorded from the CA1 area of the hippocampus using eLab after anesthetizing the animals with a ketamine-xylazine combination (70 +7 mg/kg). The prolactin levels were measured using the ELISA method after serum preparation. The findings indicate that the use of levetiracetam as an anticonvulsant drug resulted in a significant decrease in the amount of prolactin and spike number of convulsive activities compared to the chronic group. However, the amplitudes of convulsive activities did not show a significant difference between the control and other treatment groups. In conclusion, investigating the possibility of subclinical seizures and utilizing anticonvulsant medications in hyperprolactinemia that is resistant to treatment are crucial in treating infertility.

In vivo electrophysiological study of vitamin D3 protective effects on PTZ-induced seizures in rats.

Background and purpose: The purpose of the current study was to investigate the protective effects of acute and chronic administration of different doses of vitamin D3 on pentylenetetrazol (PTZ)-induced epileptiform activities in rats. Experimental approach: Sixty Wistar rats in chronic and acute groups were used in this study. In the chronic groups, animals received vitamin D3 at 50, 100, and 150 µg/kg; vitamin D3 (50 µg/kg, i.p.) + diazepam (0.1 mg/kg, i.p.), and almond oil (i.p.) daily for two weeks whereas, in the acute groups the animal received a single dose of chemicals just 30 min before PTZ administration. The electrophysiological recording was performed by implanting a unilateral bipolar electrode in the pyramidal cell layer of the CA1 region of the hippocampus. Epileptic activities were induced by intraperitoneal injection of PTZ (80 mg/kg, i.p.). The spike count and amplitude were analyzed using the eTrace software. Finding/Results: Chronic administration of all doses of vitamin D3 and its combination with diazepam significantly reduced both spike counts and amplitudes following PTZ administration. While the acute doses were ineffective. Conclusion and implication: The results of the study indicated that chronic but not acute administration of vitamin D3 has a protective effect on PTZ-induced epileptiform activity in rats.

Menthol Dissolved in Dimethyl Sulfoxide Protects Against Epileptiform Activity Induced by Pentylenetetrazol in Male Rats.

Introduction: This research aims to investigate the protective action of menthol dissolved in dimethyl sulfoxide (DMSO) on experimental epileptiform activity induced by the intraperitoneal (IP) injection of pentylenetetrazol (PTZ) in male rats. Methods: Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to five equal groups. The control animals received normal saline (200 µL) and the rest four cohorts were considered as treatment. Menthol was dissolved in DMSO and intraperitoneally injected at the doses of 100, 200, and 400 mg/kg into the first, second, and third groups (M100, M200, and M400 V=200 µL), respectively. The fourth treatment was injected with the solvent (200 µL). The animals were anesthetized, then underwent cranial surgery and a recording electrode was implanted in the stratum radiatum of the hippocampal carbonic anhydrase 1 (CA1) region (AP=-2.76 mm, ML=-1.4 mm and DV=3 mm). The seizure activity was induced by PTZ (IP) and assessed by counting and measuring amplitudes of the spikes for 10 minutes using the eTrace program. Results: Menthol was observed to significantly reduce the activity level of PTZ-induced epileptiform activity, as well as exert a protective and inhibitory action on proconvulsant effect of DMSO in a dose-dependent manner. Conclusion: Menthol can potentially be used as an adjuvant to prevent seizure activity. Highlights: Dimethyl sulfoxide (DMSO) induces proconvulsant effects, significantly increasing spike counts.Menthol 100 mg/kg also stimulates seizure activity, leading to a substantial spike count increase.Menthol 200 and 400 mg/kg exhibit inhibitory effects, decreasing seizure activity and spike counts. Plain Language Summary: In this study, we explored the potential protective effects of menthol, dissolved in dimethyl sulfoxide (DMSO), on experimentally induced epileptiform activity in male rats. Our research involved thirty adult male Wistar rats, divided into five groups. While the control group received normal saline, the remaining four groups were treated with different doses of menthol in DMSO. The rats underwent surgery, and electrodes were implanted in the hippocampal region for recording. Using pentylenetetrazol (PTZ) to induce seizure activity, we observed that menthol, administered at varying doses, significantly reduced the level of epileptiform activity triggered by PTZ. Notably, menthol also demonstrated a protective and inhibitory effect on the proconvulsant action of DMSO, and this effect was dose-dependent. In simpler terms, our findings suggest that menthol has the potential to be used as an additional treatment to prevent seizure activity. This means that incorporating menthol, especially at specific doses, may offer a protective influence against epileptic events. This research sheds light on a promising avenue for potential therapeutic interventions, emphasizing the importance of further exploration of menthol's role in epilepsy prevention. Ultimately, our study opens the door to considering menthol as a valuable component in the development of strategies to mitigate the impact of seizures.

Artemisinin and l-carnitine combination therapy alters the erythrocytes redox status.

Hematopoiesis is a sensitive target of artemisinin (ART) and its derivatives, and hemolysis is one of their commonly reported side effects. l-carnitine (LC), an amino acid derivative involved in lipid metabolism, is beneficial for hematological parameters. Sixty adult laboratory mice were randomly divided into six groups. Group I (control) received saline and corn oil; groups II and III received therapeutic (50 mg/kg) and toxic (250 mg/kg) doses of ART, respectively; groups IV and V received 370 mg/kg LC along with the 50 and 250 mg/kg ART, respectively; and group VI received 370 mg/kg LC. Drugs were administered orally for 7 consecutive days. The erythrocyte glucose 6-phosphate dehydrogenase (G6PD), catalase (CAT), and peroxidase (POX) activity, and the reduced glutathione (GSH) level were assessed by colorimetric methods. ART reduced the G6PD activity both at therapeutic and toxic doses. The therapeutic dose of ART reduced the CAT activity and the GSH level, nonsignificantly. The toxic dose of ART reduced the CAT activity and increased the POX activity. LC reduced the G6PD, CAT, and POX activities and increased GSH level. The therapeutic dose of ART and LC showed synergy in reducing the G6PD activity. LC and ART combination reduced POX activity and increased GSH level without any significant effect on the CAT activity. Inhibition of G6PD may be a potentially new mechanism of ART action. Coadministration of LC with ART or following treatment with ART may have protective effects on erythrocytes.

Stimulatory and inhibitory effects of morphine on pentylenetetrazol-induced epileptic activity in rat.

AIMS: The present study attempts to evaluate the effects of different doses of morphine on experimental epileptiform activity caused by pentylenetetrazol (PTZ) in rats. METHODS: Thirty adult male rats were assigned to saline (n = 5), morphine (2, 5, and 10 mg/kg, n = 15), naloxone (1 mg/kg, n = 5), and pre-treated with naloxone+morphine (1 + 10 mg/kg, n = 5) groups. The animals were anesthetized with ketamine + xylazine (80 + 8 mg/kg), and then a bipolar electrode was implanted into the CA1 (AP: -2.76 mm, ML: -1.4 mm and DV: 3 mm). To evaluate the effects of drugs on spike count and their amplitudes by elab amplifier, after drug administration for 25 min, PTZ (80 mg/kg, i.p.) was injected to induce epileptiform activity. Finally, diazepam (10 mg/kg) was used to suppress epileptic activity. RESULTS: The results revealed that morphine at a dose of 2 mg/kg decreased, and at doses of 5 and 10 mg/kg had an increasing effect on seizure-like events (SLEs). Nevertheless, morphine at a dose of 10 mg/kg enhanced SLEs significantly (p < 0.01). Naloxone at a dose of 1 mg/kg had no significant effect on the spike count but increased amplitude of them (p < 0.001). Moreover, being pretreatment with naloxone at a dose of 1 mg/kg, the morphine group showed significantly increased in the spike count (p < 0.05). CONCLUSIONS: Morphine has biphasic effects on PTZ-induced epileptiform activities that way at a low dose has an inhibitory effect, but if the dose is increased, it will intensify the desired event and that the stimulatory effects of morphine appear not to be via opioid receptors.

Acute and chronic effects of morphine on Low-Mg2+ ACSF-induced epileptiform activity during infancy in mice hippocampal slices.

Interaction of morphine and seizure is complex. Mouse brain hippocampal slices were used to estimate how acute and chronic morphine treatment alters the low-magnesium artificial cerebrospinal fluid (LM-ACSF)-induced seizure activity. Hippocampal slices were taken from the normal and morphine-treated mice. The normal mice received saline while the other group (morphine-treated mice) received morphine daily for 5 consecutive days. Saline/morphine administration was performed subcutaneously (s.c, 0.1 mL) at postnatal days 14-18. Hippocampal slices of all animals were perfused with LM-ACSF followed by different morphine concentrations (0, 10, 100, and 1000 µM) or naloxone (10 µM). Changes in the spike count were considered as indices for quantifying the seizure activity in the slices. In hippocampus of both groups perfused with 10 or 1000 µM morphine, epileptiform activity was suppressed while it was potentiated at 100 µM morphine. The excitatory effect of morphine at 100 µM was stronger in normal mice (acute exposure) than in dependent mice (chronic exposure). Naloxone suppressed the epileptiform activities in both groups. Suppressive effect of naloxone was more significant in morphine-treated mice than in normal mice. The seizure activity in morphine-dependent mice was more labile than that of normal mice. It can be concluded that morphine had a biphasic effect on LM-ACSF-induced epileptiform activities in both groups. The occurrence of seizure was comparable in acute and chronic exposure of morphine but strength of the effect was considerably robust in normal mice. The down regulation of opioid receptors in chronic exposure is likely to be responsible for these differences.

Interactive Effects of Exercise, Sex Hormones, and Transient Congenital Hypothyroidism on Long-Term Potentiation in Hippocampal Slices of Rat Offspring.

INTRODUCTION: The long-term adverse effects of transient thyroid function abnormalities at birth on intellectual development are proven. The effect of exercise increases in the presence of sex hormones. The current study aimed at investigating the possibility that a combination of sex hormones and exercise has synergistic effects on neural plasticity in Transient Congenital Hypothyroidism (TCH) rats. METHODS: To induce hypothyroidism in the mothers, Propylthiouracil (PTU) was added to drinking water (100 mg/L) on the 6th day of gestation and continued until the 21st Postnatal Day. From Postnatal Day (PND) 28 to 47, the female and male pups received 17ß-estradiol and testosterone, respectively. The mild treadmill exercise began 30 minutes after the sex hormones or vehicle administration. On PND 48, electrophysiological experiments were performed on brain slices. RESULTS: Increase of Long-Term Potentiation (LTP) was observed in sedentary-non-hormone female rats of TCH group, compared with that of the control. The exercise enhanced LTP in control rats, but the hormones showed no significant effect. The effect of exercise and sex hormone was not significant in the TCH group. The combination of exercise and testosterone enhanced LTP in TCH male rats, while the combination of exercise and estradiol or each of them individually did not produce such an effect on LTP in TCH female rats. CONCLUSION: The study findings showed an increase in excitatory transmission despite the returning of thyroid hormone levels to normal range in TCH female rats. Also a combination treatment including exercise and testosterone enhanced LTP in male rats of TCH group, which was a gender-specific event.

The effect of selective opioid receptor agonists and antagonists on epileptiform activity in morphine-dependent infant mice hippocampal slices.

Hippocampal slices of mouse brain were used to estimate how selective agonist and antagonist of opioid receptors alter Low-Mg+2 artificial cerebrospinal fluid (LM-ACSF)-induced epileptiform activities in normal and morphine-dependent mice. Brain slices were obtained from control and morphine-dependent mice. The morphine-dependent group received morphine once a day for 5 consecutive days, and the control group received saline. All injections were administered subcutaneously (s.c) in a volume of 0.1mL on postnatal days 14-18. Brain slices were perfused with LM-ACSF along with selective agonist and antagonist of µ, κ and δ opioid receptors. Changes in spike count per unit of time were used as indices to quantify the effects of LM-ACSF exposure in the slices. In both groups, DAMGO (selective µ opioid receptor agonist) and DPDPE (selective δ opioid receptor agonist) suppressed while Dyn-A (selective κ opioid receptor agonist) potentiated the epileptiform activity. Meanwhile, BFN-A (selective µ opioid receptor antagonist) recovered epileptiform activity in normal brain slices but not in morphine-dependent ones. NTI (selective δ opioid receptor antagonist) and nor-BNI (selective κ opioid receptor antagonist) decreased epileptiform activity. It seems that the excitatory effect of morphine on epileptiform activity was mediated through kappa receptors and its inhibitory effect was mediated via the mu receptor and, to a lesser degree, through the delta receptor. The pattern of effect was similar in normal and morphine-dependent slices, but the intensity of the effect was significantly stronger in normal mice. Finding of this study might be considered for further research and attention in epilepsy treatment.