Design: Controlled prospective animal study Setting: Research la

Design: Controlled prospective animal study. Setting: Research laboratory at academic medical center. Subjects: Conscious unrestrained young and aged male mice. Interventions: Mice were treated with the TRPV1 agonist dihydrocapsaicin, a TRPM8 inhibitor (“compound 5″), or their combination and the effects on core temperature

(T-core) were measured by implanted thermocouples and wireless transponders. Measurements and Main Results: TRPV1 agonist dihydrocapsaicin produced a dose-dependent (2-4 mg/kg Selleckchem LY3023414 s.c.) drop in T-core. A loading dose followed by continuous infusion of dihydrocapsaicin produced a rapid and prolonged ( bigger than 6 hr) drop of T-core within the therapeutic range (32-34 degrees C). The hypothermic effect of dihydrocapsaicin was augmented in aged mice and was not desensitized with repeated administration. TRPM8 inhibitor “compound 5″ (20 mg/kg s.c.) augmented the drop in core temperature during cold exposure (8 degrees C). When “compound 5″ (30 mg/kg) was combined with dihydrocapsaicin (1.25-2.5 mg/kg), the drop in

T-core was amplified and prolonged. Conclusions: Activating warm receptors (TRPV1) produced rapid and lasting hypothermia in young and old mice. Furthermore, hypothermia induced by TRPV1 agonists was potentiated and prolonged by simultaneous inhibition of TRPM8.”
“Ethnopharmacological relevance: Byrsonima verbascifolia is used in folk medicine to treat diarrhea, Selleck MI-503 intestinal LXH254 infections, chronic wounds, Chagas disease, inflammation and as a diuretic. However there is no investigation regarding the Byrsonima verbascifolia hydrometanolic extract (BVHME) used during gestation. Materials and methods: The pregnant females were randomly divided

into 5 groups. Control group received saline plus DMSO (1%) in a volume of 0.1 mL/10 g (b.w.), via gavage, for at least 15 days prior to mating and throughout the gestational period. The Pre-treatment group received the BVHME, via gavage, at a dose of 50 mg/kg (b.w.) for at least 15 days prior to mating and up to the appearance of the vaginal plug. The Organogenesis group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, on the 5-15th gestational day. The Gestational group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to the 18th day of pregnancy). The Pre+Gestational group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, for at least 15 days prior to mating and up to throughout the gestational period. The clinical signals of maternal and fetuses toxicity were evaluated, as the mutagenicity and immunomodulation tests were performed.

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