Octreotide ameliorates inflammation and apoptosis in acute and kindled murine PTZ paradigms.
In the present study, the role of octreotide (OCT) in pentylenetetrazole (PTZ) kindling as well as in acute convulsion models was evaluated. Mice were allocated in groups as (1) control saline; (2) acute PTZ (PTZ-a; 60 mg/kg, i.p.), as a single convulsive dose; and (3) kindled (PTZ-k) receiving nine subconvulsive doses of PTZ (40 mg/kg, i.p.) for 17 days. Groups 4-7 received either valproic acid (VPA) 50 mg/kg or OCT (50 μg/kg, Sandostatin®) 30 min by oral gavage before PTZ-a or PTZ-k. The median seizure stage, latency onset of first stage 4/5 seizures, and incidence of convulsing animals were recorded. Cortical dopamine (DA), tumor necrosis factor (TNF)-α, interleukin (IL)-10, caspase (Casp)-3, myeloperoxidase (MPO), and nitric oxide (NO) were assessed in addition to inducible nitric oxide synthase (iNOS) that was evaluated immunohistochemically in a different set of groups. OCT halted PTZ-induced epilepsy delaying convulsion latency via modulating MPO and TNF-α and normalizing IL-10 with both treatment regimens. In PTZ-k, it decreased Casp-3 activity, NO level, and iNOS immunoreactivity. OCT in both paradigms decreased DA concentration. The current investigation implicates a crucial role for OCT in modulating PTZ-induced kindling by regulating inflammatory and apoptotic effects.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
M Y
MY
Al-Shorbagy
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. noha.nassar@pharma.cu.edu.eg.
Noha N
NN
Nassar
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D010433:Pentylenetetrazole; D009195:Peroxidase / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D014635:Valproic Acid; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D015282:Octreotide; D004298:Dopamine; D010433:Pentylenetetrazole
Cortex; Dopamine; Epilepsy; Hippocampus; Inducible nitric oxide synthase; Kindling; Mice; Octroetide; Pentylenetetrazole; Tumor necrosis factor; Valproate
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