ABSTRACT
BACKGROUND: Recent experimental evidence suggests that lipopolysaccharide (LPS)-induced hypothermia is an adaptive thermoregulatory strategy against immunological challenge in rats. We hypothesized that the hormones which are predominantly responsible for energy homeostasis may have efferent signaling roles for development of the hypothermia. AIM: The aim of the study was to evaluate the changes of hypothalamic-pituitary-thyroid (HPT) and hypothalamic- pituitary-adrenal (HPA) axis hormones, leptin and erythropoietin at various phases of LPS-induced hypothermia such as the initial phase, nadir and the end of the response in blood sampled rats. MATERIAL AND METHODS: Body temperature of adult male albino Wistar rats was recorded by biotelemetry. E. coli O111:B4 LPS (250 µg/kg, ip) was injected alone or with SC-560, a cyclooxygenase-1 selective inhibitor (1 mg/kg, sc). RESULTS: Serum FT4 levels elevated at the initial phase, but FT3 levels decreased at nadir and remained low at the end of the response. Meanwhile, no change was observed in TSH levels. Serum adrenocorticotropic hormone (ACTH) levels reduced at the initial phase and serum corticosterone levels decreased at nadir without any change in serum corticotropin-releasing hormone (CRH) levels throughout the hypothermia. Serum leptin levels increased only at the end of the response. No change was observed in the levels of serum erythropoietin. SC-560 treatment abolished both LPS-induced hypothermia and respective hormonal changes. CONCLUSION: Data suggest that HPT axis hormones may contribute to development of LPS-induced hypothermia in rats. Data also support the view that leptin may have a role for the recovery of hypothermic response.
Subject(s)
Biomarkers/analysis , Body Temperature/drug effects , Hypothalamo-Hypophyseal System/drug effects , Hypothermia/metabolism , Lipopolysaccharides/toxicity , Pituitary-Adrenal System/drug effects , Adrenocorticotropic Hormone/metabolism , Animals , Corticosterone/metabolism , Cyclooxygenase Inhibitors/pharmacology , Erythropoietin/metabolism , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothermia/chemically induced , Leptin/metabolism , Male , Mice , Pituitary-Adrenal System/metabolism , Pyrazoles/pharmacology , Rats, Wistar , Thyrotropin/metabolism , Thyroxine/metabolismABSTRACT
This study was undertaken to evaluate the role of brain PGD2 activity during PTZ induced seizures in rats. Potentiation of endogenous PGD2 activity caused an anti-convulsant effect. Thus, after PGD2 injection (5 microg/icv) the latency of generalized tonic clonic convulsions was prolonged. ZK 118.182, a stable analogue of PGD2, dose-dependently inhibited the incidence and the intensity of seizures when injected at doses of 1-100 ng/icv. But on the other hand, inhibition of PGD2 activity either by a D-type PG receptor antagonist (AH 6809; 50 ng/icv) or by a PGD synthase inhibitor (sodium selenite; 0.2 microg/icv) produced a proconvulsant effect by increasing the incidence and the intensity of the seizures. These findings indicate that endogenous PGD2 activity in the brain may have a specific inhibitory role for the initiation and propagation of PTZ induced seizures in rats.