اثرات درمانی کوئرستین در مدل سپسیس القایی با لیپوپلی‌ساکارید در دوز پایین در سگ و مقایسه آن با هیدروکورتیزون

نوع مقاله : فارماکولوژی

نویسندگان

1 گروه علوم درمانگاهی، دانشکده دامپزشکی شهید چمران اهواز، اهواز، ایران

2 گروه علوم درمانگاهی، دانشکده دامپزشکی دانشگاه شهید چمران اهواز، اهواز، ایران

3 گروه علوم پایه، دانشکده دامپزشکی دانشگاه شهید چمران اهواز، اهواز، ایران

4 گروه پاتوبیولوژی، دانشکده دامپزشکی دانشگاه شهید چمران اهواز، اهواز، ایران

چکیده

زمینه: مدل سپسیس با دوز پایین در سگ، شرایط مناسبی را برای مطالعه داروهای جدید در دسترس قرار می‌دهد. لیپوپلی-ساکاریدها (LPS) ، یکی از اجزاء اصلی غشای بیرونی باکتری‌ها، نقش مهمی در شروع پاتوژنز بیماری دارند. سپسیس ناشی از القاء لیپوپلی‌ساکارید، تا حد زیادی در حیوانات آزمایشگاهی مطالعه شده است، اما اهمیت آن در سگ‌ها، عمدتا ناشناخته است. هدف: هدف از انجام تحقیق حاضر، ارزیابی تأثیرگذاری کوئرستین در مقایسه با هیدروکورتیزون، بر تغییرات بالینی، هماتولوژیکی و نارسایی اندام‌ها (کبد و قلب)، در مدل سپسیس القاء شده توسط لیپوپلی‌ساکارید با دوز پایین، در سگ بود. روش‌کار: بدین منظور، 15 قلاده سگ سالم از نظر بالینی و از نژاد مخلوط، به‌صورت تصادفی، به سه گروه مساوی تقسیم شدند. سگ‌های گروه A (کنترل)،LPS (g/kgμ 1/0 ،IV) را دریافت کردند. گروه B، مشابه گروه A بود، با این تفاوت که،40 دقیقه پس از تزریق LPS، کوئرستین (mg/kg 2، IV، یک‌بار) تزریق شد. گروه C، مشابه گروه B بود؛ با این تفاوت که به‌جای کوئرستین، هیدروکورتیزون (mg/kg 2، IV، یک‌بار)، تجویز شد. مقادیر سرمی گلوکز، پروتئین تام، آلبومین، ALT، AST، ALP، کراتین کیناز ایزوآنزیم ماهیچه/مغز (CK-MB)، LDH و تروپونین قلبی I (cTn-I)، با استفاده از کیت‌های تجاری اندازه‌گیری شدند. نتایج: در گروه کنترل، پس از تزریق LPS، کاهش معنی‌داری در تعداد تام گلبول‌های قرمز (RBCs)، هموگلوبین (Hb) و هماتوکریت(HCT) ؛ و هم‌چنین، افزایش معنی‌داری در فعالیت سرمی آنزیم‌های AST، ALP ، LDH ، ایزوآنزیم CK-MB و cTn-I نشان دادند) 05/0(P

تازه های تحقیق

Afshari, M., Rahimmalek, M., Miroliaei, M. (2018) Variation in polyphenolic profiles, antioxidant and antimicrobial activity of different  achil- lea species as natural sources of antiglycative compounds. Chem Biodivers, 15(8), e1800075. https://doi.     org/10.1002/cbdv.     201800075.

PMID:  29779268.

Asgary, S., Naderi, G.H., Askari, M.S. (2005) Pro- tective effect of flavonoids against red blood cell hemolysis by free radicals. Exp Clin Cardi- ol, 10(2), 88-90. PMID: 19641665.

Balk,   R.A.   (2014)   Systemic   inflammatory re-


sponse syndrome (SIRS). Virulence, 5(1),  20-

26.   https://doi.   org/10.4161/viru.27135.

PMID: 24280933.

Baskurt, O.K., Gelmont, D., Meiselman, H.J. (1998) Red blood cell deformability in sepsis. Am J Respir Crit Care Med, 157(2), 421-427. https://doi. org/10.1164/ajrccm.157.2.9611103. PMID:  9476853.

Ceylan-Isik, A.F., Zhao, P., Zhang, B., Xiao, X., Su,

G. and Ren, J. (2010) Cardiac overexpression of metallothionein rescues cardiac contractile dysfunction and endoplasmic reticulum stress but not autophagy in sepsis. J Mol Cell Cardi- ol, 48(2), 367–378. https://doi. org/10.1016/j. yjmcc.2009.11.003.  PMID: 19914257.

Das, D.K., Chakraborty, A., Sinha, M., Manna, K., Mukherjee, D., Chakraborty, A., Bhattacharjee, S., Dey, S. (2013) Modulatory role of quer- cetin against gamma radiation-mediated bio- chemical and morphological alterations of red blood cells. Int J Radiat Biol, 89(6), 471-481. https://doi. org/10.3109/09553002.2013.76798 9.  PMID: 23363054.

De David, C., Rodrigues,  G.,  Bona,  S.,  Meur- er, L., Gonzalez-Gallego, J., Tunon, M.J. (2011) Role of quercetin in preventing thio- acetamide-induced liver injury in rats. Tox-  icol Pathol, 39(6), 949-957. https://doi. org/10.1177/0192623311418680.

PMID: 21885874.

De Vries, F., Leuschner, J., Jilma, B., Derhaschnig,

U. (2013) Establishment of a low dose canine endotoxemia model to test  anti-inflammato-  ry drugs: effects of prednisolone. Int J Immu- nopathol Pharmacol, 26(4), 861-869. https:// doi. org/ 10.1177/039463201302600404. PMID: 24355221.

Egert, S., Wolffram, S., Bosy-Westphal, A., Boesch-Saadatmandi, C., Wagner, A.E., Frank, J., Rimbach, G., Mueller, M.J. (2008) Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr, 138(9), 1615-1621. https://doi. org/10.1093/jn/138.9.1615. PMID: 18716159.

Geraets, L., Moonen, H., Brauers, K., Wouters, E.F.,   Bast,  A.,   Hageman,   G.J.   (2007). Di-

 

 

 

etary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells. J Nutr, 137(10), 2190-2195. https://doi. org/10.1093/jn/137.10.2190. PMID: 17884996.

Goyette, R.E., Key, N.S., Ely, E.W. (2004) Hema- tologic changes in sepsis and their therapeu-  tic implications. Semin Respir Crit Care Med, 25(6), 645-659. https://doi. org/10.1016/10.105

5/s-2004-860979.  PMID: 16088507.

Ikizler, M., Erkasap, N., Dernek, S., Kural, T., Kaygisiz, Z. (2007) Dietary polyphenol quer- cetin protects rat hearts during reperfusion: en- hanced antioxidant capacity with chronic treat- ment. Anadolu Kardiyol Derg, 7(4),   404-410.

PMID: 18065337.

Javadi, B., Sahebkar, A. (2017) Natural products with anti-inflammatory and immunomodula- tory activities against autoimmune myocar- ditis. Pharmacol Res, 124, 34-42. https://doi. org/10.1016/j.phrs.2017.07.022.

PMID: 28757189.

Kitagawa, S., Sakamoto, H., Tano, H. (2004) In- hibitory effects of flavonoids on free radical-in- duced hemolysis and their oxidative effects on hemoglobin. Chem Pharm Bull (Tokyo), 52(8), 999-1001. https://doi. org/10.1248/cpb.52.999.

PMID: 15305001.

Landry, D.W., Oliver, J.A. (2001) The pathogene- sis of vasodilatory shock. N Engl J Med, 45(8), 588–595. https://doi. org/ 10.1056/NEJM- ra002709.  PMID: 11529214.

Liao, Y., Lin, J. (2015) Quercetin intraperitoneal ad- ministration ameliorates lipopolysaccharide-in- duced systemic inflammation in mice. Life Sci, 137(1),   89-97.   https://doi.  org/10.1016/j.lfs.

2015.07.015. PMID: 26209141.

Penalva, R., Gonzalez-Navarro, C.J., Gamazo, C., Esparza, I., Irache, J.M. (2017) Zein nanoparti- cles for oral delivery of quercetin: Pharmaco- kinetic studies and preventive anti-inflamma- tory effects in a mouse model of endotoxemia. Nanomedicine, 13(1), 103-110. https://doi. org/

10.1016/j.nano.2016.08.033. PMID: 27615118.

Punithavathi, V.R., Stanely Mainzen Prince, P. (2011) The cardioprotective effects of a com- bination of quercetin and α-tocopherol on   iso-


proterenol-induced myocardial infarcted rats. J Biochem Mol Toxicol, 25(1), 28-40. https://doi. org/  10.1002/jbt.20339.  PMID: 20979156.

Reinboth, M., Wolffram, S., Abraham, G., Unge- mach, F.R., Cermak, R. (2010) Oral bioavail- ability of quercetin from different quercetin glycosides in dogs. Br J Nutr, 104, 198-203. https://doi. org/ 10.1017/S000711451000053X. PMID:  20230651.

Rochwerg, B., Oczkowski, S.J., Siemieniuk, R.A.C., Agoritsas, T., Belley-Cote, E., D'Ara- gon, F., Duan, E., English, S., Gossack-Keenan, K., Alghuroba,  M.,  Szczeklik,  W., Menon, K.,  Alhazzani,  W., Sevransky,  J.,   Vandvik, P., Annane, D., Guyatt, G. (2018) Cortico- steroids in Sepsis: An Updated Systematic Review and Meta-Analysis. Crit Care Med, 46(9),  1411-1420.  https://doi.  org/   10.1097/

CCM.0000000000003262.  PMID:  29979221.

Shapiro, H., Lev, S., Cohen, J., Singer P. (2009) Polyphenols in the  prevention  and  treatment of sepsis syndromes: rationale and pre-clinical evidence. Nutrition, 25(10), 981-997. https:// doi. org/ 10.1016/j.nut.2009.02.010. PMID: 19502006.

Valentova, K., Sima, P., Rybkova, Z., Krizan, J., Malachova, K., Kren V. (2016) (Anti) muta- genic and immunomodulatory properties of quercetin glycosides. J Sci Food Agric, 96(5), 1492-1499.  https://doi. org/10.1002/jsfa.7251.

PMID:  25960089.

Vasquez-Garzon, V.R., Arellanes-Robledo, J., Garcia-Roman, R., Aparicio-Rautista, D.I., Villa-Trevino, S. (2009) Inhibition of reac-  tive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism. Free Radic Res, 43(2), 128-137. https://doi. org/ 10.1080/10715760802626535. PMID: 19115120.

Virginia, D.V., Owen, H., Poapolathep, A., Mario,

G. (2017) Natural substances as new potential strategies for the treatment of  leishmaniosi- sin dogs. Am J Anim Vet Sci, 12(3), 169-175. https://doi.     org/10.3844/ajavsp.2017.169.175.

Volbeda, M., Wetterslev, J., Gluud, C., Zijlstra, J.G., van der Horst, I.C.C., Keus, F. (2015) Glu- cocorticosteroids for sepsis: systematic review with  meta-analysis  and  trial  sequential anal-

 

 

ysis. Intensive Care Med, 41(7), 1220-1234. https://doi. org/ 10.1007/s00134-015-3899-6. PMID: 26100123.

Wan,  Y.,   Tang,  M.H.,  Chen,  X.C.,  Chen,   L.J.,

Wei, Y.Q., Wang, Y.S. (2014) Inhibitory ef-  fect of liposomal quercetin  on  acute  hepati- tis and hepatic fibrosis induced by concanav- alin A. Braz J Med Biol Res, 47(8), 655-661. https://doi. org/10.1590/1414-431x20143704. PMID: 25098714.

Yang, H., Song, Y., Liang, Y.N., Li, R. (2018) Quer- cetin treatment improves renal function and protects the kidney in a rat model of adenine-in- duced chronic kidney disease. Med Sci Monit, 24,    4760-4766.    https://doi.    org/10.12659/

MSM.909259.  PMID: 29987270.

Yao, Z., Gu, Y., Zhang, Q., Liu, L., Meng, G., Wu,

H., Xia, Y., Bao, X., Shi, H., Sun, S., Wang, X.,

Zhou, M., Jia, Q., Wu, Y., Song, K., Gao, W., Guo, C., Niu, K. (2018) Estimated daily querce- tin intake and association with the prevalence of type 2 diabetes mellitus in Chinese adults. Eur J Nutr, 11(1), e0144179. https://doi. org/ 10.1007/ s00394-018-1713-2. PMID: 29754250.

Zhang, J., Shi, L., Xu, X., Huang, S., Lu, B., Ji, L. (2014) Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism. J Zhejiang Univ Sci B, 15(12), 1039-1047. https://doi. org/ 10.1631/jzus.B1400104. PMID: 25471833.

کلیدواژه‌ها

مراجع

Afshari, M., Rahimmalek, M., Miroliaei, M. (2018) Variation in polyphenolic profiles, antioxidant and antimicrobial activity of different  achil- lea species as natural sources of antiglycative compounds. Chem Biodivers, 15(8), e1800075. https://doi.     org/10.1002/cbdv.     201800075.
PMID:  29779268.
Asgary, S., Naderi, G.H., Askari, M.S. (2005) Pro- tective effect of flavonoids against red blood cell hemolysis by free radicals. Exp Clin Cardi- ol, 10(2), 88-90. PMID: 19641665.
Balk,   R.A.   (2014)   Systemic   inflammatory re-
sponse syndrome (SIRS). Virulence, 5(1),  20-
26.   https://doi.   org/10.4161/viru.27135.
PMID: 24280933.
Baskurt, O.K., Gelmont, D., Meiselman, H.J. (1998) Red blood cell deformability in sepsis. Am J Respir Crit Care Med, 157(2), 421-427. https://doi. org/10.1164/ajrccm.157.2.9611103. PMID:  9476853.
Ceylan-Isik, A.F., Zhao, P., Zhang, B., Xiao, X., Su,
G. and Ren, J. (2010) Cardiac overexpression of metallothionein rescues cardiac contractile dysfunction and endoplasmic reticulum stress but not autophagy in sepsis. J Mol Cell Cardi- ol, 48(2), 367–378. https://doi. org/10.1016/j. yjmcc.2009.11.003.  PMID: 19914257.
Das, D.K., Chakraborty, A., Sinha, M., Manna, K., Mukherjee, D., Chakraborty, A., Bhattacharjee, S., Dey, S. (2013) Modulatory role of quer- cetin against gamma radiation-mediated bio- chemical and morphological alterations of red blood cells. Int J Radiat Biol, 89(6), 471-481. https://doi. org/10.3109/09553002.2013.76798 9.  PMID: 23363054.
De David, C., Rodrigues,  G.,  Bona,  S.,  Meur- er, L., Gonzalez-Gallego, J., Tunon, M.J. (2011) Role of quercetin in preventing thio- acetamide-induced liver injury in rats. Tox-  icol Pathol, 39(6), 949-957. https://doi. org/10.1177/0192623311418680.
PMID: 21885874.
De Vries, F., Leuschner, J., Jilma, B., Derhaschnig,
U. (2013) Establishment of a low dose canine endotoxemia model to test  anti-inflammato-  ry drugs: effects of prednisolone. Int J Immu- nopathol Pharmacol, 26(4), 861-869. https:// doi. org/ 10.1177/039463201302600404. PMID: 24355221.
Egert, S., Wolffram, S., Bosy-Westphal, A., Boesch-Saadatmandi, C., Wagner, A.E., Frank, J., Rimbach, G., Mueller, M.J. (2008) Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr, 138(9), 1615-1621. https://doi. org/10.1093/jn/138.9.1615. PMID: 18716159.
Geraets, L., Moonen, H., Brauers, K., Wouters, E.F.,   Bast,  A.,   Hageman,   G.J.   (2007). Di-
 
 
 
etary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells. J Nutr, 137(10), 2190-2195. https://doi. org/10.1093/jn/137.10.2190. PMID: 17884996.
Goyette, R.E., Key, N.S., Ely, E.W. (2004) Hema- tologic changes in sepsis and their therapeu-  tic implications. Semin Respir Crit Care Med, 25(6), 645-659. https://doi. org/10.1016/10.105
5/s-2004-860979.  PMID: 16088507.
Ikizler, M., Erkasap, N., Dernek, S., Kural, T., Kaygisiz, Z. (2007) Dietary polyphenol quer- cetin protects rat hearts during reperfusion: en- hanced antioxidant capacity with chronic treat- ment. Anadolu Kardiyol Derg, 7(4),   404-410.
PMID: 18065337.
Javadi, B., Sahebkar, A. (2017) Natural products with anti-inflammatory and immunomodula- tory activities against autoimmune myocar- ditis. Pharmacol Res, 124, 34-42. https://doi. org/10.1016/j.phrs.2017.07.022.
PMID: 28757189.
Kitagawa, S., Sakamoto, H., Tano, H. (2004) In- hibitory effects of flavonoids on free radical-in- duced hemolysis and their oxidative effects on hemoglobin. Chem Pharm Bull (Tokyo), 52(8), 999-1001. https://doi. org/10.1248/cpb.52.999.
PMID: 15305001.
Landry, D.W., Oliver, J.A. (2001) The pathogene- sis of vasodilatory shock. N Engl J Med, 45(8), 588–595. https://doi. org/ 10.1056/NEJM- ra002709.  PMID: 11529214.
Liao, Y., Lin, J. (2015) Quercetin intraperitoneal ad- ministration ameliorates lipopolysaccharide-in- duced systemic inflammation in mice. Life Sci, 137(1),   89-97.   https://doi.  org/10.1016/j.lfs.
2015.07.015. PMID: 26209141.
Penalva, R., Gonzalez-Navarro, C.J., Gamazo, C., Esparza, I., Irache, J.M. (2017) Zein nanoparti- cles for oral delivery of quercetin: Pharmaco- kinetic studies and preventive anti-inflamma- tory effects in a mouse model of endotoxemia. Nanomedicine, 13(1), 103-110. https://doi. org/
10.1016/j.nano.2016.08.033. PMID: 27615118.
Punithavathi, V.R., Stanely Mainzen Prince, P. (2011) The cardioprotective effects of a com- bination of quercetin and α-tocopherol on   iso-
proterenol-induced myocardial infarcted rats. J Biochem Mol Toxicol, 25(1), 28-40. https://doi. org/  10.1002/jbt.20339.  PMID: 20979156.
Reinboth, M., Wolffram, S., Abraham, G., Unge- mach, F.R., Cermak, R. (2010) Oral bioavail- ability of quercetin from different quercetin glycosides in dogs. Br J Nutr, 104, 198-203. https://doi. org/ 10.1017/S000711451000053X. PMID:  20230651.
Rochwerg, B., Oczkowski, S.J., Siemieniuk, R.A.C., Agoritsas, T., Belley-Cote, E., D'Ara- gon, F., Duan, E., English, S., Gossack-Keenan, K., Alghuroba,  M.,  Szczeklik,  W., Menon, K.,  Alhazzani,  W., Sevransky,  J.,   Vandvik, P., Annane, D., Guyatt, G. (2018) Cortico- steroids in Sepsis: An Updated Systematic Review and Meta-Analysis. Crit Care Med, 46(9),  1411-1420.  https://doi.  org/   10.1097/
CCM.0000000000003262.  PMID:  29979221.
Shapiro, H., Lev, S., Cohen, J., Singer P. (2009) Polyphenols in the  prevention  and  treatment of sepsis syndromes: rationale and pre-clinical evidence. Nutrition, 25(10), 981-997. https:// doi. org/ 10.1016/j.nut.2009.02.010. PMID: 19502006.
Valentova, K., Sima, P., Rybkova, Z., Krizan, J., Malachova, K., Kren V. (2016) (Anti) muta- genic and immunomodulatory properties of quercetin glycosides. J Sci Food Agric, 96(5), 1492-1499.  https://doi. org/10.1002/jsfa.7251.
PMID:  25960089.
Vasquez-Garzon, V.R., Arellanes-Robledo, J., Garcia-Roman, R., Aparicio-Rautista, D.I., Villa-Trevino, S. (2009) Inhibition of reac-  tive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism. Free Radic Res, 43(2), 128-137. https://doi. org/ 10.1080/10715760802626535. PMID: 19115120.
Virginia, D.V., Owen, H., Poapolathep, A., Mario,
G. (2017) Natural substances as new potential strategies for the treatment of  leishmaniosi- sin dogs. Am J Anim Vet Sci, 12(3), 169-175. https://doi.     org/10.3844/ajavsp.2017.169.175.
Volbeda, M., Wetterslev, J., Gluud, C., Zijlstra, J.G., van der Horst, I.C.C., Keus, F. (2015) Glu- cocorticosteroids for sepsis: systematic review with  meta-analysis  and  trial  sequential anal-
 
 
ysis. Intensive Care Med, 41(7), 1220-1234. https://doi. org/ 10.1007/s00134-015-3899-6. PMID: 26100123.
Wan,  Y.,   Tang,  M.H.,  Chen,  X.C.,  Chen,   L.J.,
Wei, Y.Q., Wang, Y.S. (2014) Inhibitory ef-  fect of liposomal quercetin  on  acute  hepati- tis and hepatic fibrosis induced by concanav- alin A. Braz J Med Biol Res, 47(8), 655-661. https://doi. org/10.1590/1414-431x20143704. PMID: 25098714.
Yang, H., Song, Y., Liang, Y.N., Li, R. (2018) Quer- cetin treatment improves renal function and protects the kidney in a rat model of adenine-in- duced chronic kidney disease. Med Sci Monit, 24,    4760-4766.    https://doi.    org/10.12659/
MSM.909259.  PMID: 29987270.
Yao, Z., Gu, Y., Zhang, Q., Liu, L., Meng, G., Wu,
H., Xia, Y., Bao, X., Shi, H., Sun, S., Wang, X.,
Zhou, M., Jia, Q., Wu, Y., Song, K., Gao, W., Guo, C., Niu, K. (2018) Estimated daily querce- tin intake and association with the prevalence of type 2 diabetes mellitus in Chinese adults. Eur J Nutr, 11(1), e0144179. https://doi. org/ 10.1007/ s00394-018-1713-2. PMID: 29754250.
Zhang, J., Shi, L., Xu, X., Huang, S., Lu, B., Ji, L. (2014) Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism. J Zhejiang Univ Sci B, 15(12), 1039-1047. https://doi. org/ 10.1631/jzus.B1400104. PMID: 25471833.
مجله طب دامی ایران
دوره 13، شماره 4
مهر 1398
صفحه 377-387

فایل ها

هم رسانی

ارجاع به این مقاله

آمار