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Eur J Pharmacol. 2017 Nov 15;815:241-250. doi: 10.1016/j.ejphar.2017.09.032. Epub 2017 Sep 21.

Hypothalamic pathways regulate the anorectic action of p-chloro-diphenyl diselenide in rats.

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Post-Graduation Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, Capão do Leão Campus, Pelotas, RS 96010-900, Brazil. Electronic address:
Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
Department of Physiology, School of Medicine-CIMUS, Instituto de Investigacion Sanitaria (IDIS), CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), University of Santiago de Compostela, San Francisco s/n, Santiago de Compostela (A Coruña), 15782, and Avda. Barcelona 3, 15782 Santiago de Compostela, Spain.


Behavioral studies have suggested that (p-ClPhSe)2 elicits an anorectic-like action in rats by inducing multiple effects such as satiety-enhancing effect, malaise and specific flavor; however, the molecular mechanisms underlying its anorexigenic action remain unclarified. Here, male Sprague-Dawley rats received acute and sub-chronic intraperitoneal treatments with (p-ClPhSe)2; thereafter, in vivo and ex vivo analyses were carried out. The present study reveals that the reduction of food intake resulting from a single treatment with (p-ClPhSe)2 (1mg/kg, i.p.) was associated with decreased hypothalamic levels of pro-melanin-concentrating hormone (pro-MCH) and orexin precursor. In addition, repeated administrations of (p-ClPhSe)2 (10mg/kg; i.p.) for 7 days induced sustained food intake suppression, body weight loss and white fat reduction. Measurements of brown adipose tissue content and temperature as well as data obtained from a pair-fed group indicated that the effects of (p-ClPhSe)2 on the body weight are closely related to its anorexigenic actions, ruling out the possibility of increased thermogenesis. Furthermore, (p-ClPhSe)2 reduced the hypothalamic orexin precursor levels when repeatedly administered to rats. Sub-chronic treatment with (p-ClPhSe)2 caused a decrease of serum triglyceride levels and down-regulation of hepatic cholesterol content. Therefore, the current study characterized the anorectic and reducing body weight actions of (p-ClPhSe)2 in Sprague-Dawley rats. Besides, the set of results suggests that food intake suppressant effects triggered after (p-ClPhSe)2 administration to rats are mainly related with the lower orexin levels in hypothalamus after acute and sub-chronic treatments.


Appetite suppressant; Body weight loss; Neuropeptides; Orexin; Selenium

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