Ali Hosseini-Sharifabad

Background and aims: Dracocephalum kotschyi is a medicinal plant native to Iran, which is known for its anti-inflammatory and spasmolytic properties. This study was conducted to investigate the sub-chronic adverse effects of D. kotschyi extract on biochemical and hematological biomarkers in rats, with the aim of identifying any potential adverse effects associated with long-term therapy. Methods: A total of 50 male Wistar rats were randomly allocated into 5 separate groups, each consisting of 10 rats. The extract was administered orally for 90 days at doses of 25, 75, and 300 mg/kg in three distinct groups. A control group and a vehicle-treated group were also included in this study. Following the treatment period, blood samples were collected to assess biochemical and hematological parameters. Liver and kidney tissue samples were prepared for histological examination. Mean comparisons between groups were conducted using the one-way analysis of variance (ANOVA), with P values less than 0.05 considered statistically significant. Results: The hydroalcoholic extract of D. kotschyi at a dose of 300 mg/kg significantly increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatinine (Cr). Additionally, ALT and alkaline phosphatase (ALP) levels were significantly elevated at the dose of 75 mg/kg. Other parameters, including electrolytes, glucose, lipid profiles, thyroid hormones, complete blood count (CBC), prothrombin time (PT), and international normalized ratio (INR), remained unaffected, and no tissue damage was observed in the histological examinations. Conclusion: Long-term oral administration of D. kotschyi extract at anti-inflammatory doses in rats resulted in no significant changes in the measured plasma biochemical or hematological biomarkers. However, at higher doses, there was an increase in hepatic biomarkers, as well as LDH and Cr levels, indicating potential organ toxicity associated with overdose.

Introduction: Dracocephalum kotschyi is an Iranian traditional medicine with anti-inflammatory and bronchodilatory properties. The objective of this research was to investigate the preventive effect of D. kotschyi extract in bleomycin induced fibrosis. Methods: Fibrosis was induced by intratracheal administration of a single dose of bleomycin (5 mg/kg) in rat. One group received daily administration of normal saline. Other groups were treated daily with oral administration of either hydroalcoholic or aqueous extract of D. kotschyi (20, 40, & 80 mg/kg). Another group was treated with pirfenidone (100 mg/kg). After 4 weeks daily treatments, the animals were sacrificed and the whole lungs were dissected out for biochemical and histopathological examinations. The biochemical examination included assessment of hydroxyproline and malondialdehyde levels. Results: The lung tissues in bleomycin treated groups showed severe tissue injuries. However, lung tissues in the groups that received hydroalcoholic or aqueous extracts of D. kotschyi showed mild to moderate tissue injuries. Intratracheal instillation of bleomycin significantly increased hydroxyproline and malondialdehyde biomarker levels compared with the sham group. In the positive control group treated with pirfenidone, there was a marked reduction in both hydroxyproline and malondialdehyde levels. Both hydroalcoholic and aqueous extracts of D. kotschyi significantly prevented the elevation of hydroxyproline and malondialdehyde levels at the above oral doses in comparison to the vehicle treated control group. Conclusion: Prevention of hydroxyproline and malondialdehyde elevation levels in this experiment indicates that D. kotschyi extract might be a suitable remedy for the treatment of respiratory fibrosis induced by drugs such as bleomycin.

Background: Excitotoxicity is a common pathological process in neurodegenerative diseases associated with overactivity of N-methyl-D-aspartate (NMDA) and P/Q type voltage-gated calcium (Cav2.1) channels. Omega-lycotoxin-Gsp2671g is a therapeutic tool to modulate overactive Cav2.1 (P/Q type) channels. Omega-lycotoxin binds to Cav2.1 channels with high affinity and selectivity. This study aimed to investigate the effects of Omega-lycotoxin on the cognitive impairment induced by kainic acid in rats. Methods: The effect of pre-treatment and post-treatment trials of intra-hippocampal Cornu Ammonis-3 administration of omega-lycotoxin (0.5, 1 or 2µg) was studied on the cognitive impairment induced by kainic acid in rats. The rats’ learning and memory were assessed by the passive avoidance and a single-day testing version of the Morris water maze method. Results: Omega-lycotoxin caused a significant increase in the latency of the passive avoidance test and the duration of their presence in the target area of the Morris water maze test compared to the groups treated with kainic acid (P<0.0001). There were statistically significant differences for the effects of various doses of omega-lycotoxin. The post-treatment groups showed a greater improvement than those in the pretreatment groups. Conclusion: The findings demonstrated that a single dose of omega-lycotoxin can prevent or revert the memory impairment caused by kainic acid in rats.

Ali Hosseini-Sharifabad, Mohammad Rabbani, Yasaman Seyed-Yousefi, Maryam Safavi. Clin Psychopharmacol Neurosci 2020;18:241-8. https://doi.org/10.9758/cpn.2020.18.2.241

Maryam Safavi, Ali Hosseini-Sharifabad, Yasaman Seyed-Yousefi, Mohammad Rabbani. Clin Psychopharmacol Neurosci 2020;18:81-92. https://doi.org/10.9758/cpn.2020.18.1.81

Lead is known as an environmental contaminant with neurotoxic properties. In addition, people experience different types of chronic stress, especially in developing countries. It has been established that lead or stress causes structural and physiological damages to the neural pathway like dopaminergic connections. Nevertheless, the effect of lead and restraint stress on movement behaviors when are experienced together has not been studied yet. In this study, male albino mice were randomly divided into different groups (n = 6). Lead acetate was daily injected at 15 mg/kg intraperitoneally for 2, 4, or 6 weeks. Restraint stress (6 h in a day) was applied alone or in combination with lead acetate for 2, 4, or 6 weeks. The catalepsy, akinesia, and the balance of animals were measured by bar test, elevated beam device, and rotarod to evaluate the movement disorders. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a known neurotoxin causes movement disorders, was used as positive control group. The results showed that exposure to the lead or stress or their combination for 6 weeks caused catalepsy, akinesia, and imbalance in the animals, while exposure for 2 or 4 weeks didn’t affect the movement items indices. The combination of lead and stress did not show any significant difference compared to the exposure to each of them individually. From the findings, Lead, stress, and their combination caused movement disorders in a time dependent manner. Short time exposure did not change movement behavior. The co-exposure to the lead and stress did not show additive or synergistic effects.

Introduction: Hypothyroidism is an important endocrine disorder determined by some depressed symptoms. Urtica dioica (Urticaceae) is a medicinal plant which has been traditionally used for treatment of a wide range of decreased functions of different organs. In the current study, we aimed to evaluate the effect of hydroalcoholic extract of aerial parts of U. dioica on thyroid hormones in propylthiouracil (PTU)-induced hypothyroidism in rats.Methods: Forty-two male Wistar rats were randomly divided into 7 groups including control, PTU, different doses of Urtica dioica hydroalcoholic extract (UDHAE) treated and levothyroxine treated groups. The animals in various groups received water (control group) or water containing 0.1% W/V PTU and then injected saline (control group) or 25, 50, 100, 150 mg/kg UDHAE, respectively for 4 weeks. Positive control group was fed levothyroxine 0.5 mg/kg during the PTU treatment. Then, the blood samples were collected and the levels of thyroxine (T4), triiodothyronine (T3), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) measured via the Elisa method.Results: The data showed that PTU decreased the blood level of thyroid hormones but increased TSH, significantly. The 50 or 100 mg/kg doses of UDHAE remarkably increased the blood level of T3 and FT3. The 50 mg/kg doses of UDHAE increased the blood level of T4. None of the UDHAE doses showed significant change in the TSH levels. 25 and 150 mg/kg doses of UDHAE did not change the PTU- diminished level of thyroid related hormones.Conclusion: The findings suggest that 50 mg/kg dose of UDHAE has stimulatory effect on thyroid gland function and raises plasma T3 & T4 & FT3 levels. UDHAE at the dose of 50 or 100 mg/kg could enhance blood level of T3 and FT3 perhaps by increase in T4 to T3 transformation. Higher doses of UDHAE could not increase the level of these hormones probably due to the presence of inhibitory materials.

Memory impairment is one of the greatest concerns when it comes to long-term CNS-affecting drug administration. Drugs like gabapentin, pregabalin and baclofen are administered in a long-term period in conditions such as epilepsy, neuropathic pain, spasticity associated with spinal cord injury or multiple sclerosis. Despite their wide spread use, few data are available on the effects of these drugs on cognitive functions, such as learning memory. In the present study, the effects of long-term administration of gabapentin, pregabalin and baclofen on memory were investigated in a comparative manner. Male Wistar rats received intraperitoneal (i.p.) injection of gabapentin (30 mg/kg), pregabalin (30 mg/kg), baclofen (3 mg/kg), combination of gabapentin/baclofen (30/3 mg/kg) and combination of pregabalin/baclofen (30/3 mg/kg) once a day for 3 weeks respective to their groups. After the end of treatments, rat memories were assessed using the object-recognition task. The discrimination and recognition indices (RI and DI) in the T2 trials were used as the memory indicating factors. The results showed that daily i.p. administrations of pregabalin but not gabapentin or baclofen significantly decreased DI and RI compared to saline group. In combination groups, either gabapentin or pregabalin impaired discrimination between new and familiar objects. Our findings suggested that pregabalin alone or in combination with baclofen significantly caused cognitive deficits.

Potassium bromide (KBr), an old antiepileptic agent, is illegally used in pharmaceutical or food industries to improve the product appearance. KBr has been proven to influence several pathways which are important in memory formation. Therefore, the present study aimed to evaluate the effect of KBr on spatial working memory using object recognition task (ORT). Rats received a single dose of KBr (50, 100 or 150 mg/kg), per oral, in acute treatment. KBr long term effects were also studied in animals receiving 50 mg/kg/day of KBr for 28 consecutive days. At the end of treatments, animals underwent two trials of ORT, five min each. In the first trial (T₁), animals encountered with two identical objects for exploration. After 1 h, the animals were exposed to a familiar and an unfamiliar object (T₂). The exploration times for discrimination (D) and recognition (R) as well as the frequency of exploration for any objects were determined. Acute administration of 150 mg/kg of KBr significantly decreased the discrimination and recognition indices (RI and DI) (P < 0.01) compared to the control. However, lower doses failed to influence the animals’ performance in the test. In addition, long term administration of KBr remarkably diminished the DI and RI and the frequency of exploration (P < 0.05). The results of this study indicate that acute doses of KBr as high as 150 mg/kg are required to hamper memory function in ORT. However, cognitive impairment occured with lower doses of KBr when the duration of treatment is extended.