The effect of diacamph hydrochloride on the cortisol content in the blood of rats with diabetes mellitus modelled against the immobilization stress background

Authors

  • R. D. Zakrutnyi National University of Pharmacy, Ukraine
  • S. Yu. Shtrygol’ National University of Pharmacy, Ukraine
  • S. I. Merzlikin National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/cphj.14.1270

Keywords:

diacamph hydrochloride, cortisol, diabetes mellitus, chronic immobilization stress

Abstract

The aim of our study was to determine the effect of diacamph hydrochloride, an original antihyperglycemic drug, on the cortisol content in the blood of animals with a combined model of diabetes mellitus and chronic stress. The experiment was performed on mature male rats. Diabetes mellitus of the 1-st type was modelled by a single injection of alloxan monohydrate (150 mg/kg subcutaneously) and chronic immobilization stress was induced by putting the animals into tight boxes for 16 hours daily over 15 days period beginning from the 11-th day after alloxan injection. It has been found that the concentration of cortisol in the blood plasma of animals of the control pathology group increased essentially as compared to the intact control group. The concentration increased from 77.51 ng/mol to 421.65 ng/mol, i.e. became 5.4 times higher (p<0.001). It indicates intensity of corticosteroid-mediated mechanisms of stress-response behaviour against the background of modelled diabetes mellitus. Taking contrainsular properties of corticosteroids into account such effect of prolonged immobilization against the background of diabetes mellitus should be considered to be particularly unfavourable. Diacamph hydrochloride (intraperitoneal injections of 25 mg/kg daily) not only reduced glycemia, but also was likely to decrease the blood cortisol content to 172.0 ng/ml on the average as compared to the value in the control pathology group (p<0.001). Bemithyl, a classical actoprotector, used as a reference drug (intraperitoneal injections of 50 mg/kg daily) was found to be statistically significantly inferior to diacamph hydrochloride (p<0.001) as it decreased the cortisol concentration only to 253.35 ng/ml on the average. The results testify stress-protective properties of diacamph hydrochloride under diabetes mellitus conditions and substantiate the prospects of its further studying as a potential adaptogenic and stress-protective drug. The mechanism of diacamph hydrochloride action is associated with its effect on endocrinous mechanisms of stress reaction.

References

Киричек Л.Т. Стресспротекторы в эксперименте и в клинике. – Х.: ИПП «Контраст», 2008. – 304 с.

Паньків В.И. // Новости медицины и фармации. – 2011. – №383. – С. 22-24.

Пат. на корисну модель 70732 Україна, МПК (2012.01) С 07 D 235/16 (2006.01), А 61 К 31/4184 (2006.01), А 61 Р 9/00 (±)-Цис-3-(2′-бензімід-азоліл)-1,2,2-триметил-циклопентанкарбонової кислоти гідрохлорид, який виявляє актопротекторну дію / С.І.Мерзлікін, Р.Д.Закрутний, С.Ю.Штриголь, С.М.Коваленко. Заявник та патентовласник: Національний фармацевтичний університет. – №u2011 13990. Заявл.: 28.11.2011. Опубл.: 25.06.2012. – Бюл. №12. – 4 с.

Питкевич Э.С., Лозинский М.О., Лызиков А.Н. и др. Бемитил (bemitylum) – антигипоксант, актопротектор: фармакологические эффекты и клиническое применение в медицине: Информ. бюл. – К., 2001. – 44 с.

Chyun D.A., Meikus G.D., Katten D.M. et al. // Bio. Rest. Nurs. – 2008. – Vol. 7. – P. 279-288.

Dave K.R., Katyare S.S. // J. of Endocrinol. – 2002. – Vol. 175, №1. – P. 241-250.

Jacobson A.M., de Groot M., Samson J.A. // Diabetes Care. – 1994. – Vol. 17, №4. – P. 267-274.

Imanyama I., Plotnikoff R., Corneya K. et аl. // Health and Quality of Life Outcomes. – 2011. – Vol. 9. – P. 115.

Wilfley D., Berkowitz R., Goebel-Fabbri A. et al. // Diabetes Care. – 2011. – Vol. 34. – P. 858-860.

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Published

2014-09-12

Issue

Section

Pre-clinical studies of new drugs