title: Strain-dependent effects of long-term treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins.
abstract: Oxidative stress is implicated in the pathogenesis of both hypertension and epileptogenesis, therefore it could be used as a tool for studying co-morbidity of hypertension and epilepsy. Clinical data suggest that melatonin is a potent antioxidant that is effective in the adjunctive therapy of hypertension and neurodegenerative diseases. The present study aimed to explore and compare the efficacy of chronic pretreatment with melatonin infused via subcutaneous osmotic mini-pumps for 14 days (10 mg/kg per day) on kainic acid (KA)-induced status epilepticus, oxidative stress and expression of heat shock protein (HSP) 72 in spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. SHRs showed higher lipid peroxidation (LP) in the frontal cortex and hippocampus and decreased cytosolic superoxide dismutase (SOD/CuZn) production in the frontal cortex compared to Wistar rats. Status epilepticus (SE) induced by KA (12 mg/kg, i.p.) was accompanied by increased LP and expression of HSP 72 in the hippocampus of the two strains and increased SOD/CuZn production in the frontal cortex of SHRs. Melatonin failed to suppress seizure incidence and intensity though the latency for seizure onset was significantly increased in SHRs. Melatonin attenuated the KA-induced increase in the level of LP in the hippocampus both in SHRs and Wistar rats. However, an increased activity in SOD/CuZn and mitochondrial SOD Mn as well as reduced expression of HSP 72 in the hippocampus was observed only in Wistar rats pretreated with melatonin. Taken together, the observed strain differences in the efficacy of chronic melatonin exposure before SE suggest a lack of a direct link between the seizure activity and the markers of oxidative stress and neurotoxicity.
authors: Department of Biology, Medical University of Pleven, 1 Kliment Ohridski Str., Pleven 5800, Bulgaria.
authors: Milena
authors: M
authors: Atanasova
authors: Zlatina
authors: Z
authors: Petkova
authors: Daniela
authors: D
authors: Pechlivanova
authors: Petya
authors: P
authors: Dragomirova
authors: Alexander
authors: A
authors: Blazhev
authors: Jana
authors: J
authors: Tchekalarova
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013045:Species Specificity; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D013482:Superoxide Dismutase; D008550:Melatonin; D007608:Kainic Acid
keywords: HSP; Heat shock protein; KA; Kainic acid; LP; Melatonin; Oxidative stress; ROS; SE; SHRs; SOD/CuZn; Spontaneously hypertensive rats; Wistar rats; cytosolic superoxide dismutase; heat shock protein; kainic acid; lipid peroxidation; reactive oxygen species; spontaneously hypertensive rats; status epilepticus