The Effect of Oleoylethanolamide (OEA) Add-On Treatment on Inflammatory, Oxidative Stress, Lipid, and Biochemical Parameters in the Acute Ischemic Stroke Patients: Randomized Double-Blind Placebo-Controlled Study.

Methods: Sixty patients with a mean age of 68.60 ± 2.10 comprising 29 females (48.33%), who were admitted to an academic tertiary care facility within the first 12 hours poststroke symptoms onset or last known well (LKW), in case symptom onset time is not clear, were included in this study. AIS was confirmed based on a noncontrast head CT scan and also neurological symptoms. Patients were randomly and blindly assigned to OEA of 300 mg/day (n = 20) or 600 mg/day (n = 20) or placebo (n = 20) in addition to the standard AIS treatment for three days. A blood sample was drawn at 12 hours from symptoms onset or LKW as the baseline followed by the second blood sample at 72 hours post symptoms onset or LKW. Blood samples were assessed for inflammatory and biochemical parameters, oxidative stress (OS) biomarkers, and lipid profile. Results: Compared to the baseline, there is a significant reduction in the urea, creatinine, triglyceride, high-density lipoprotein, cholesterol, alanine transaminase, total antioxidant capacity, malondialdehyde (MDA), total thiol groups (TTG), interleukin-6 (IL-6), and C-reactive protein levels on the follow-up blood testing in the OEA (300 mg/day) group. In patients receiving OEA (600 mg/day) treatment, there was only a significant reduction in the MDA level comparing baseline with follow-up blood testing. Also, the between-group analysis revealed a statistically significant difference between patients receiving OEA (300 mg/day) and placebo in terms of IL-6 and TTG level reduction when comparing them between baseline and follow-up blood testing. Conclusion: OEA in moderate dosage, 300 mg/day, add-on to the standard stroke treatment improves short-term inflammatory, OS, lipid, and biochemical parameters in patients with AIS. This effect might lead to a better long-term neurological prognosis.

Neuronal degeneration and oxidative stress in the SNc of 6-OHDA intoxicated rats; improving role of silymarin long-term treatment.

Progressive loss in dopaminergic neurons (DA) of substantia nigra pars compacta (SNc) leads to Parkinson's disease with a hypothesis of oxidative stress generation. The present study was conducted to determine the long-term efficacy of silymarin (SM) post-treatment on 6-OHDA-induced oxidative stress in the SNc of male rats. Male Wistar rats were received 6-OHDA (8 µg/rat) into SNc. After 3 weeks, as recovery period, the animals were treated with i.p. injection of SM at different doses of 100, 200, or 300 mg/kg for 15 days. At the end of the treatment, motor function, neuronal cell count, antioxidant enzymes, and lipid peroxidation and tyrosine hydroxylase (TH) activities were evaluated in the ventral midbrain tissue. The 6-OHDA significantly decreased (p ≤ 0.05) motor function, antioxidant enzyme activity, GSH level, and GSH/GSSG ratio and caused an augmentation in GSSG and lipid peroxidation level. The 6-OHDA also reduced the population of neurons and TH expression. The SM repaired the 6-OHDA-induced motor impairment, antioxidant enzyme suppression, and TH down-regulation. All three doses of SM could restore the MDA level to the normal range in the 6-OHDA-lesioned rats and could reversed the effect of 6-OHDA on GSH, GSSG level, and GSH/GSSG ratio. The SM treatment significantly and dose-dependently increased (p ≤ 0.001) the total number of surviving neurons in the SNc. Silymarin chronic treatment restored the brain's antioxidant capacity and salvaged neurons from oxidative stress-induced neurodegeneration. The SM could also improve motor function in parkinsonian animals by increasing TH expression. These results recommend that application of SM over initial clinical stages may depict a hopeful approach versus PD. However, more research is needed to confirm this issue.

The effect of acute and repeated administration of buspirone, 8-OHDPAT and fluoxetine on haloperidol-induced extrapyramidal symptoms.

OBJECTIVE: The aim of this study was to investigate the effect of buspirone, as a partial agonist of 5-HT1A receptors, 8-hydroxy-2-[di-n-propylamino]-tetralin (8-OH-DPAT) as an agonist of 5-HT1A receptors and fluoxetine as a selective serotonin reuptake inhibitor on haloperidol-induced extrapyramidal symptoms (EPS) in male Wistar rats. MATERIALS AND METHODS: The experiments were performed on 66 male Wistar rats weighing 200-240g. The rats were divided into 11 groups (n=6). Extrapyramidal symptoms were induced by haloperidol injection 1mg/kg intraperitoneally (i.p.). To investigate the effect of serotonergic drugs on haloperidol-induced extrapyramidal symptoms, 8-OHDPAT (1 mg/kg), buspirone (10 mg/kg), and fluoxetine (1 mg/kg) were injected before haloperidol in an acute and 7 consecutive day's pre-treatment injection(s) mode. Extrapyramidal symptoms such as catalepsy and motor balance were assessed by the bar test and rotarod, respectively. FINDINGS: The results demonstrated that i.p. injection of haloperidol induced significant motor imbalance and catalepsy (p≤0.001) in rats. Data analysis showed that i.p. injection of buspirone (10 mg/kg) significantly decreased catalepsy compared with the control group. The attenuation of haloperidol-induced extrapyramidal symptoms was observed with 8-OHDPAT treatment. Treatment with fluoxetine did not affect the motor coordination caused by haloperidol. CONCLUSION: It may be concluded that buspirone and 8-OHDPAT improves extrapyramidal symptoms in a haloperidol-induced Parkinsonism model probably via activation of 5-HT1A receptors. However, further investigations should be carried out to clarify the exact mechanism of interaction between 5-HT1A and DA receptors.