The Effect of Brotizolam Induced Appetite on Serum Ghrelin Levels in Mice

Year 2021, , 73 - 76, 19.08.2021

Atakan Öztürk , Aliye Sağkan Öztürk

https://doi.org/10.17944/mkutfd.894485

Abstract

Objective: Appetite is affected by the metabolic profile, infections and nutritional shape in domestic animals. Regulation of appetite involves many complex physiological processes. Ghrelin is well known appetite-enhancing hormone. The appetite is also managed by the lateral hypothalamus. On the other hand, the ventromedial nucleus is most commonly associated with satiety. Brotizolam, member of the 1,4-benzodiazepines derivative, is blocking the activity of the ventromedial hypothalamus and used to increase appetite in domestic animals. The aim of this study was to investigate the impact of brotizolam on serum ghrelin levels, enhancer appetite hormone.Methods: A total of 16 mice were equally assigned to two groups as control (0.9% NaCl, IP) and brotizolam (2 μg/kg, IP). Blood samples was collected 30 min after the administration in both groups. Serum ghrelin levels were determined by enzyme linked immunoassay.Results: There was a significance differences between control and brotizolam groups (P<0.001). The results of the study showed that the administration of brotizolam increased serum ghrelin levels.Conclusion: Brotizolam, which suppresses ventromedial hypothalamus and satiety, can activate appetite by activation of the lateral hypothalamus and increase in ghrelin levels.In addition, ghrelin may be used as an endocrine marker of appetite.

Keywords

Brotizolam, Ghrelin, Appetite

Brotizolamla İndüklenen İştahın Farelerde Ghrelin Seviyeleri Üzerine Etkisi

Abstract

Amaç: Evcil hayvanlarda iştah, metabolik profil, enfeksiyon ve beslenme şeklinden etkilenmektedir. İştahın düzenlenmesi pek çok karmaşık fizyolojik süreci içerir. Ghrelin en iyi bilinen iştah arttırıcı hormondur. İştah da lateral hipotalamus tarafından yönetilir. Öte yandan, ventromedial çekirdek çoğunlukla tokluk ile ilişkilidir. 1,4-benzodiazepin türevinin bir üyesi olan brotizolam, ventromedial hipotalamusun aktivitesini bloke eder ve evcil hayvanlarda iştahı artırmak için kullanılır. Bu çalışmanın amacı, brotizolamın iştah artırıcı hormon olan serum ghrelin düzeylerine etkisini araştırmaktır.Yöntem: Toplam 16 fare, kontrol (%0,9 NaCl, IP) ve brotizolam (2 μg/kg, IP) olarak 2 eşit gruba ayrıldı. Her iki grupta da uygulamadan 30 dakika sonra kan örnekleri toplandı. Serum ghrelin seviyeleri, Enzyme-Linked Immunoassay ile belirlendi.Bulgular: Kontrol ve brotizolam grupları arasında anlamlı bir fark vardı (P<0.001). Çalışmanın sonuçları, brotizolam uygulamasının serum ghrelin düzeylerini artırdığını gösterdi.Sonuç: Ventromedial hipotalamus ve tokluğu baskılayan brotizolam, lateral hipotalamusun aktivasyonu ve ghrelin düzeylerinin artması ile iştahı aktive edebili. Ayrıca ghrelin iştahın endokrin belirteci olarak kullanılabilir.

Keywords

Brotizolam, Ghrelin, İştah, İştah

References

• Blundell JE, Lawton CL, Hill AJ: Mechanisms of appetite control and their abnormalities in obese patients. Horm Res. 39(3): 72-6, 1993. https://doi.org/10.1159/000182788
• Murphy KG, Bloom SR: Gut hormones in the control of appetite. Exp Physiol. 89: 507-516, 2004. https://doi.org/10.1016/j.tem.2004.06.002
• Perry B, Wang Y: Appetite regulation and weight control: the role of gut hormones. Nutrition and Diabetes. 2: 26, 2012. https://doi.org/10.1038/nutd.2011.21
• Vettor R, Fabris R, Pagano C, Federspil G: Neuroendocrine regulation of eating behavior. J Endocrinol Invest. 25: 836-854, 2002. https://doi.org/10.1007/BF03344047
• Small CJ, Bloom SR: Gut hormones and the control of appetite. Trends Endocrinol Metab. 15: 259- 263, 2004. https://doi.org/10.1016/j.tem.2004.06.002
• Tschöp M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R, Folwaczny C: Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest. 24: 19-21, 2001. https://doi.org/10.1007/BF03351037
• Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR: Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab. 88: 3989-3992, 2003. https://doi.org/10.1210/jc.2003-030630
• Danneberg P, Bauer R, Böke-Kuhn K, Hoefke W, Kuhn FJ, Lehr E, Walland A: General pharmacology of brotizolam in animals. Arzneimittelforschung. 36(3A): 540–551, 1986.
• Cho HJ, Jo K, Yi H, Cho SM, Abd El-Aty AM, Kim MK, Han SB, Oh JH, Kwon CH, Shim JH, Shin HC: Development and validation of a liquidchromatography method with electrosprayionization tandem mass spectrometry for thedetermination of brotizolam residues in beef and commercial whole milk. Biomed Chromatogr. 25: 1061–1066, 2011. https://doi.org/10.1002/bmc.1579
• Van Reenen CG, Hopster H, Van der Werf JT, Engel B, Buist WG, Jones RB, Blokhuis HJ, Korte SM: The benzodiazepine brotizolam reduces fear in calves exposed to a novel object test. Physiology and Behavior. 96: 307–314, 2009.https://doi.org/10.1016/j.physbeh.2008.10.016
• Schreiber W, Schulz W: Anorexia in cattle: results of treatment with Mederantil. Prakt Tierarzt. 70: 32–7, 1989.
• Neumayer M, Neumayer B, Schill H, Justus C: Studies on the effect of brotizolam (Mederantil) on anorexia in neonatal calves. Tierärztliche Umschau. 49(2): 103-104, 1994.
• Moloney AP, Hanrahan JP, Quirke JF, Hackett IJ: The effect of Mederantil on feed intake by cattle and sheep. Irish Veterinary Journal. 43(2): 45-49, 1990.
• Dynes RA, Ankersmit AEL, Poppi DP, Sykes AR & Barrell GK: Effects of fasting and an opioid antagonist on food intake in lambs infected with intestinal parasites. Proceedings of the New Zealand Society of Animal Production. 51: 371-374, 1991.
• Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL et al. Ghrelin. Mol Metab. 4(6): 437–460, 2005. https://doi.org/10.1016/j.molmet.2015.03.005
• Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 402: 656–660, 1999. https://doi.org/10.1038/45230
• Romero CEM, ZANESCO A: The role of leptin and ghrelin on the genesis of obesity. Revista de Nutrição. 19(1): 85-91, 2006. https://doi.org/10.1590/S1415-52732006000100009
• Sagkan Ozturk A, Guzel M, Kontas Askar T, Aytekin I: Evaluation of the hormones responsible for the gastrointestinal motility in cattle with displacement of the abomasum ghrelin motilin and gastrin. Vet Rec. 172: 636-640, 2013. https://doi.org/10.1136/vr.101322
• Sagkan Ozturk A, Kontas Askar T: Evaluation of motility hormones in dairy cattle with omasal impaction and caecal dilatation. Kafkas Univ Vet Fak Derg. 21: 919–922, 2015. https://doi.org/10.9775/kvfd.2015.13802
• Sagkan Ozturk A, Demır EA, Ozturk A: Prokinetics stimulate the increase of ghrelin in mice. Bratisl Lek Listy. 117: 726–729, 2016. https://doi.org/10.4149/BLL_2016_139
• Cady G, Landeryou T, Garratt M, Kopchick JJ, Qi N, Garcia-Galiano D, Elias CF, Myers MG Jr, Miller RA, Sandoval DA, Sadagurski M: Hypothalamic growth hormone receptor (GHR) controls hepatic glucose production in nutrient-sensing leptin receptor (LepRb) expressing neurons. Mol Metab. 6(5): 393-405, 2017. https://doi.org/10.1016/j.molmet.2017.03.001
• Cabral A, Fernandez G, Tolosa MJ, Rey Moggia Á, Calfa G, De Francesco PN, Perello M: Fasting induces remodeling of the orexigenic projections from the arcuate nucleus to the hypothalamic paraventricular nucleus, in a growth hormone secretagogue receptor-dependent manner. Mol Metab. 32: 69-84, 2020. https://doi.org/10.1016/j.molmet.2019.11.014
• Druce MR, Neary NM, Small CJ, Milton J, Monteiro M, Patterson M, Ghatei MA, Bloom SR: Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers. Int J Obes (Lond). 30: 293-296, 2006. https://doi.org/10.1038/sj.ijo.0803158
• Brobeck JR: Mechanism of the development of obesity in animals with hypothalamic lesions. Physiol Rev. 26: 541–559, 1946. https://doi.org/10.1152/physrev.1946.26.4.541
• Tschöp M, Smiley D, Heiman ML: Ghrelin induces adiposity in rodents. Nature. 407: 908–913, 2000. https://doi.org/10.1038/35038090
• Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu Tet al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 86(10): 4753-8, 2001. https://doi.org/10.1210/jcem.86.10.7885
• Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS: A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 50: 1714–1719, 2001. https://doi.org/10.2337/diabetes.50.8.1714
• Olszewski PK, Li D, Grace MK, Billington CJ, Kotz CM, Levine AS: Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus. Peptides. 24: 597–602, 2003. https://doi.org/10.1016/s0196-9781(03)00105-0
• Yadav R, Suri M, Mathur R, Jain S: Effect of procainization of ventromedial nucleus of hypothalamus on the feeding behavior of rats. J Clin Biochem Nutr.44(3): 247-252, 2009. https://doi.org/10.3164/jcbn.08-158
• Lee DJ, Elias GJB, Lozano AM: Neuromodulation for the treatment of eating disorders and obesity. Ther Adv Psychopharmacol. 8(2): 73-92, 2018. https://doi.org/10.1177/2045125317743435
• Sagkan Ozturk A, Aydin M, Bozkurt YA, Kuçukgul A, Ozturk A. Short term effects of experimental gastric outlet obstruction and truncal vagotomy on gut hormones. Biotech Histochem. 2021 Mar 16:1-9. https://doi.org/10.1080/10520295.2021.1896780