Zorana KOVACEVIC, R. Marko CINCOVIC, Dragica STOJANOVIC, Branislava BELIC, Milanka JEZDIMIROVIC, Radojica DJOKOVIC, Ivana DAVIDOV

Influence of Ketoprofen Application on Lipid Mobilization, Ketogenesis and Metabolic Status in Cows during Early Lactation

Geçiş dönemindeki süt ineklerinin metabolik fonksiyonlarında değişiklikler negatif enerji dengesinin sonucudur. Bu da esterleşmemiş yağ asitlerinin (NEFA) ve beta-hidroksibütirat (BHB) düzeylerindeki artışı takiben lipit mobilizasyonu ve ketogeneze yol açar. Bu yüzden yüksek lipit mobilizasyonu ve ketogenez yangısal tepkimeler ile düzenlenir ve (veya?) tersi de söz konusu. Bu çalışmanın amacı, ineklerde ketoprofen uygulanması ile yüksek lipit mobilizasyonu, ketogenez ve metabolik adaptasyonun özellikleri arasındaki ilişkileri incelemektir. Ketoprofen doğum sonrası dönemde ineklerde art arda üç gün, 3 mg/kg dozunda intramüsküler olarak uygulandı. Kontrol grubu ketoprofen uygulanmayan 15 inekten oluşturuldu. Kan örnekleri doğum sonrası birinci ve ikinci haftada coccygeal toplardamardan alındı. Kontrol grubu ile karşılaştırıldığında, ketoprofen uygulaması NEFA, BHB ve total bilirubin düzeylerini azaltırken, glikoz, albümin ve kolesterol düzeylerinde ise artışa neden oldu. Bizim sonuçlarımız, kontrol grubuyla karşılaştırıldığında ketoprofen uygulanmasının AST aktivitesinde azaldığını gösterdi. İneklerin %66.7'si normalin üzerinde NEFA ve BHB değerine sahip, yüksek lipoliz ve ketogenez yoğunluğunda artış mevcuttu; çünkü bu hayvanlara ketoprofen uygulanmadı. Kontrol grubundaki inekler kuvvetle muhtemel 2 ila 2.4 kat daha fazla yüksek lipid mobilizasyonu ve ketogenez durumuna sahipti. Biz NEFA ve BHB ile metabolik parametreler arasındaki yüksek düzeyde uyum olduğunu bulduk. Bu ilişki deney grubu hayvanlarında daha düşüktü ve doğum sonrasında hemen ketoprofenin kullanımının lipit mobilizasyon ve ketojenezi erken laktasyon döneminde düşürdüğü ve metabolik adaptasyonun bu iki sürecin yoğunluğuna bağlı olduğu sonucuna varabiliriz.

Ketoprofen Uygulamasının Süt İneklerindeki Erken Laktasyon Döneminde Lipit Mobilizasyon, Ketogenez ve Metabolik Adaptasyon Üzerine Etkisi

Changes in metabolic functions in transition dairy cows represent a result of negative energy balance. This leads to increased lipid mobilization and ketogenesis, followed by increased concentrations of non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB). Hence, high lipid mobilization and ketogenesis modulate inflammation response and vice versa. The aim of this study was to investigate correlations between ketoprofen administration, high lipid mobilization, ketogenesis and characteristics of metabolic adaptation in cows. Ketoprofen was administered intramuscularly in the concentration of 3 mg/kg, during three consecutive days in 15 postpartum cows. The control group included 15 cows which were not treated with ketoprofen. Blood samples were taken from coccygeal vein, after calving, in the first and second week of the postpartum period. When compared with control, ketoprofen administration decrease the levels of NEFA, BHB and total bilirubin, increase levels of glucose, albumin and cholesterol. Our results showed decreased activity of AST in ketoprofen treated cows in comparison with control group. There was an increase in the intensity of lipolysis and ketogenesis in 66.7% of cows, with NEFA and BHB values over the optimal results, because ketoprofen was not applied to these animals. Cows in the control group were 2 or 2.4 times more likely to come to a state of increased lipid mobilization and ketogenesis. We have found high concordance between NEFA and BHB, and metabolic parameters. This correlation was lower in experimental group of cows hence we can conclude that the use of ketoprofen immediately after calving reduces lipid mobilization and ketogenesis during early lactation and the metabolic adaptation dependence on the intensity of these two processes.

PDF

___

Ingvartsen KL: Feeding- and management-related diseases in the transition cow. Anim Feed Sci Technol, 126, 175-213, 2006. DOI: 10.1016/j. anifeedsci.2005.08.003
Mulligan FJ, Doherty ML: Production diseases of the transition cow. Vet J, 176, 3-9, 2008. DOI: 10.1016/j.tvjl.2007.12.018
Quiroz-Rocha GF, LeBlanc S, Duffield T, Wood D, Leslie KE, Jacobs RM: Evaluation of prepartum serum cholesterol and fatty acids concentrations as predictors of postpartum retention of the placenta in dairy cows. J Am Vet Med Assoc, 234, 790-793, 2009. DOI: 10.2460/ javma.234.6.790
Sordillo LM, Contreras GA, Aitken SL: Metabolic factors affecting the inflammatory response of periparturient dairy cows. Anim Health Res Rev, , 53-63, 2009. DOI: 10.1017/S1466252309990016
Calder PC: The relationship between the fatty acid composition of immune cells and their function. Prostag Leukotr Ess, 79, 101-108, 2008. DOI: 10.1016/j.plefa.2008.09.016
Serhan CN, Chiang N, Van Dyke TE: Resolving inflammation: Dual antiinflammatory and pro-resolution lipid mediators. Nat Rev Immunol, 8, 361, 2008. DOI: 10.1038/nri2294
Bernabucci U, Ronchi B, Lacetera N, Nardone A: Influence of body condition score on relationships between metabolic status and oxidative stress in periparturient dairy cows. J Dairy Sci, 88, 2017-2026, 2005. DOI: 10.3168/jds.S0022-0302(05)72878-2
Douglas GN, Rehage J, Beaulieu AD, Bahaa AO, Drackley JK: Prepartum nutrition alters fatty acid composition in plasma, adipose tissue, and liver lipids of periparturient dairy cows. J Dairy Sci, 90, 2941- , 2007. DOI: 10.3168/jds.2006-225
Goff JP: Macromineral physiology and application to the feeding of the dairy cow for prevention of milk fever and other periparturient mineral disorders. Anim Feed Sci Technol, 126, 237-257, 2006. DOI: 10.1016/j. anifeedsci.2005.08.005
Amann R, Peskar BA: Anti-inflammatory effects of aspirin and sodium salicylate. Eur J Pharmacol, 447, 1-9, 2002. DOI: 10.1016/S0014- (02)01828-9
Banting A, Banting S, Heinonen K, Mustonen K: Efficacy of oral and parenteral ketoprofen in lactating cows with endotoxin-induced acute mastitis. Vet Rec, 163, 506-509, 2008. DOI: 10.1136/vr.163.17.506
Donalisio C, Barbero R, Cuniberti B, Vercelli C, Casalone M, Re G: Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows. J Vet Pharmacol Ther, 36, 130-139, 2013. DOI: 10.1111/j.1365- 2012.01396.x de Zentella PM, Vázquez-Meza H, Piña-Zentella G, Pimentel
L, Piña E: Non-steroidal anti-inflammatory drugs inhibit epinephrine- and cAMP-mediated lipolysis in isolated rat adipocytes. J Pharm Pharmacol, 54, 577-82, 2002. DOI: 10.1211/0022357021778709
Vázquez-Meza H,de Zentella PM, Pardo JP, Riveros-Rosas H, Villalobos-Molina R, Piña E: Non-steroidal anti-inflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysis, BMC Biochem, 14, 13, 2013. DOI: 10.1186/1471-2091-14-13
Bertoni G, Trevisi E, Piccioli-Cappelli F: Effects of acetyl-salicylate used in postcalving of dairy cows. Vet Res Commun, 28, 217-219, 2004. DOI: 10.1023/B:VERC.0000045410.86004.03
Kushibiki S, Hodate K, Shingu H, Ueda Y, Mori Y, Itoh T, Yokomizo Y: Effects of long-term administration of recombinant bovine tumor necrosis factor ? on glucose metabolism and growth hormone secretion in steers. Am J Vet Res, 62, 794-798, 2001. DOI: 10.2460/ajvr.2001.62.794
Medzhitov R: Origin and physiological roles of inflammation. Nature : 428-435, 2008. DOI: 10.1038/nature07201
Ohtsuka H, Koiwa M, Hatsugaya A, Kudo K, Hoshi F, Itoh N, Yokota H, Okada H, Kawamura S: Relationship between serum TNF activity and insulin resistance in dairy cows affected with naturally occurring fatty liver. J Vet Med Sci, 63, 1021-1025, 2001. DOI: 10.1292/jvms.63.1021
Garcia ML, Tost D, Vilageliu J: Bioavalbility of S (+) - ketoprofen after oral administration of different mixtures of ketoprofen enantiomers to dogs. J Clin Pharmacol. 38 (12): 22S-26S, 1998.
Diaz-Reval MI, Ventura-Martinez R, Deciga-Campos M, Terron JA, Cabre F, Lopez-Munoz FJ: Evidence for a central mechanism of action of S- (+) - ketoprofen. Eur J Pharmacol. 483, 241-248, 2004. DOI: 10.1016/j. ejphar.2003.10.036
Katzung BG: Basic & Clinical Pharmacology. 6th ed., 460-477, Appleton & Lange, Norwalk, Conneticut, USA, 1995.
Brideau C, Van Staden C, Chan CC: In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats. Am J Vet Res, 62, 1755- , 2001. DOI: 10.2460/ajvr.2001.62.1755
Streppa HK, Jones CJ, Budsberg SC: Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood. Am J Vet Res, 63, 94, 2002. DOI: 10.2460/AJVR.2002.63.91
Boothe DM: Veterinary Pharmacology and Therapeutics. 8th ed., Adams HR, 433-451. Lowa State University Press. Ames. 2001.
EMEA: Ketoprofen. Summary Report, 1995. http://www.ema.europa. eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_
Report/2009/11/WC500014541.pdf , Accessed: 12.03.2015.
Nathalie CN, Tucker CB, Pearl DL, LeBlanc SJ, Leslie KE, von Keyserlingk MAG, Duffield TF: An investigation of the effects of ketoprofen following rumen fistulation surgery in lactating dairy cows. Can Vet J, 55 (5): 442-448, 2014.
Bobe G, Young JW, Beitz DC: Invited review: Pathology, etiology, prevention and treatment of fatty liver in dairy cows. J Dairy Sci, 87, 3105- , 2004. DOI: 10.3168/jds.S0022-0302(04)73446-3
Cincovic MR, Belic B, Radojicic B, Hristov S, İokovic R: Influence of lipolysis and ketogenesis to metabolic and hematological parameters in dairy cows during periparturient period. Acta Veterinaria (Belgrad), 62, 444, 2012. DOI: 10.2298/AVB1204429C
Ospina PA, Nydam DV, Stokol T, Overton TR: Evaluation of nonesterified fatty acids and ?-hydroxybutyrate in transition dairy cattle in the northeastern United States: Critical thresholds for prediction of clinical diseases. J Dairy Sci, 93, 546-554, 2010. DOI: 10.3168/jds.2009
Chapinal N, Carson ME, LeBlanc SJ, Leslie KE, Godden S, Capel M, Santos JEP, Overton MW, Duffield TF: The association of serum metabolites in the transition period with milk production and early- lactation reproductive performance. J Dairy Sci, 95, 1301-1309, 2012. DOI: 3168/jds.2011-4724
González FD, Muiño R, Pereira V,Campos R, Benedito JL: Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows. J Vet Sci, 12, 255, 2011. DOI: 10.4142/jvs.2011.12.3.251
McArt JA, Nydam DV, Oetzel GR, Overton TR, Ospina PA: Elevated non-esterified fatty acids and ?-hydroxybutyrate and their association with transition dairy cow performance. Vet J, 198, 560-570, 2013. DOI: 1016/j.tvjl.2013.08.011.
Drackley JK, Dann HM, Douglas GN, Janovick Guretzky NA, Litherland NB, Underwood JP, Loor JL: Physiological and pathological adaptations in dairy cows that may increase susceptibility to peri- parturient diseases and disorders. Ital J Anim Sci, 4, 323-44, 2005. DOI: 4081/ijas.2005.323
Bertoni G, Trevisi E, Calamari L, Lombardelli R: Additional energy and protein supplementation of dairy cows during early lactation: Milk yield, metabolic-endocrine status and reproductive performances. Zoot Nutr Anim, 24, 17-29, 1998.
Contreras GA, Sordillo LM: Lipid mobilization and inflammatory responses during the transition period of dairy cows. Comp Immunol Microb, 34, 281-289, 2011. DOI: 10.1016/j.cimid.2011.01.004
Herdt TH: Ruminant adaptation to negative energy balance. Influences on the etiology of ketosis and fatty liver. Vet Clin North Am: Food Anim Pract, 16, 15-230, 2000.
Nowroozi AA, Nazifi S, Rowshan Ghasrodashti A, Olyaee A: Prevalence of subclinical ketosis in dairy cattle in the Southwestern Iran and detection of cutoff point for NEFA and glucose concentrations for diagnosis of subclinical ketosis. Prev Vet Med, 100, 38-43, 2011. DOI: 1016/j.prevetmed.2011.02.013
TóthováC, NagyO, KovácG: Changes in the concentrations of selected acute phase proteins and variables of energetic profile in dairy cows after parturition. J Appl Anim Res, 42, 278-283, 2014. DOI: 1080/09712119.2013.842485
Moshage HJ, Janssen JA, Franssen JH, Hafkenscheid JC, Yap SH: Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation. J Clin Invest. 79, 1635-1641, 1987. DOI: 10.1172/ JCI113000
Djokovic R, Cincovic M, Kurcubic V, Petrovic M, Lalovic M, Jasovic B, Stanimirovic Z: Endocrine and metabolic status of dairy cows during transition period. Thai J Vet Med, 44 (1): 59-66, 2014.
Itoh N, Koiwa M, Hatsugaya A, Yokota H, Taniyama H, Okada H, Kudo K: Comparative analysis of blood chemical values in primary ketosis and abomasal displacement in cows. J Vet Med A, 45, 293-298, DOI: 10.1111/j.1439-0442.1998.tb00830.x
Cavestany D, Blanc JE, Kulcsar M, Uriarte G, Chilibroste P, Meikle A, Febel H, Ferraris A, Krall E: Studies of the transition cow under a pasturebased milk production system: Metabolic profiles. J Vet Med A, 52, , 2005. DOI: 10.1111/j.1439-0442.2004.00679.x
Kourounakis AP, Victoratos P, Peroulis N, Stefanou N, Yiangou M, Hadjipetrou L, Kourounakis PN: Experimental hyperlipidemia and the effect of NSAIDs. Exp Mol Pathol, 73, 135-138, 2002. DOI: 10.1006/ exmp.2002.2449
Trevisi E, Amadori M, Cogrossi S, Razzuoli E, Bertoni G: Metabolic stress and inflammatory response in high-yielding, periparturient dairy cows. Res Vet Sci, 93, 695-704, 2012. DOI: 10.1016/j.rvsc.2011.11.008
Djokovic R, Cincovic M, Belic B, Toholj B, Davidov I, Hristovska T: Relationship between blood metabolic hormones, metabolites and energy balance in Simmental dairy cows during peripartal period and lactation. Pak Vet J, 35, 163-167, 2015.