Effect of Ascending Doses of Pentoxifylline Administration on Biochemical and Hematological Parameters in Goats

Öz

Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor drug used in human and veterinary medicine to promote microcirculation. Although PTX has been used in experimental studies in goats, there is no information about its safety. The aim of this study is to determine the effect of PTX on hematological and biochemical parameters following intravenous (IV) administration of 10, 20 and 40 mg/kg doses to Hair goats. In the study were used clinically healthy 9 goats. PTX was administered IV to goats at doses of 10, 20 and 40 mg/kg. Blood samples were taken before drug administration (control, 0 hour) and 12 hours after administration, and hematological and biochemical parameters were evaluated. No local or systemic adverse effects were observed in goats after the application of PTX at different doses. After administration of PTX at 20 and 40 mg/kg doses, white blood cell (WBC) level increased, while hemoglobin (HGB) level decreased at 10 mg/kg dose (p<0.05). When compared with the 10 mg/kg dose group, WBC, red blood cell (except 40 mg/kg), HGB and hematocrit values were found to be increased in the 20 and 40 mg/kg dose groups (p<0.05). While the administration of PTX at different doses caused a general decrease in biochemical parameters (p<0.05), no change was observed in troponin I level. In conclusion, it can be stated that the administration of PTX in goats at doses of 10, 20 and 40 mg/kg caused significant changes in hematological and biochemical parameters and caution should be exercised as these temporary changes in single-dose administrations may pose a risk in repeated administrations.

Anahtar Kelimeler

• Ascending dose
• Biochemical
• Goat
• Hematological
• Pentoxifylline

Keçilere Artan Dozlarda Pentoksifilin Uygulamasının Biyokimyasal ve Hematolojik Parametrelere Etkisi

Öz

Pentoksifilin (PTX) beşerî ve veteriner hekimlikte mikrosirkülasyonun teşvik edilmesi amacıyla kullanılan non-selektif fosfodiesteraz inhibitörü bir ilaçtır. PTX keçilerde deneysel çalışmalarda kullanılmasına rağmen güvenilirliği hakkında herhangi bilgi bulunmamaktadır. Bu araştırmanın amacı Kıl keçilerine PTX’in 10, 20 ve 40 mg/kg dozlarda damar içi (IV) uygulamasını takiben hematolojik ve biyokimyasal parametreler üzerine etkisini belirlemektir. Araştırmada klinik olarak sağlıklı 9 adet keçi kullanıldı. PTX keçilere 10, 20 ve 40 mg/kg dozlarda IV yolla uygulandı. Kan örnekleri ilaç uygulaması öncesi (kontrol 0.saat) ve uygulamayı takiben 12.saatte alınarak hematolojik ve biyokimyasal parametreler değerlendirildi. PTX’in farklı dozlarda uygulaması sonrası keçilerde lokal ya da sistemik herhangi bir yan etki görülmedi. PTX’in 20 ve 40 mg/kg dozlarda uygulaması sonrası akyuvar (WBC) seviyesi artarken 10 mg/kg dozda hemoglobin (HGB) düzeyi azaldı (p<0.05). 10 mg/kg doz grubu ile karşılaştırıldığında, 20 ve 40 mg/kg doz gruplarında WBC, alyuvar (40 mg/kg hariç), HGB ve hematokrit değerlerinin arttığı belirlendi (p<0.05). PTX’in farklı dozlarda uygulaması, biyokimyasal parametrelerde genel olarak azalmaya neden olurken (p<0.05), troponin I düzeyinde herhangi bir değişiklik görülmedi. Sonuç olarak, keçilerde PTX’in 10, 20 ve 40 mg/kg dozlarda uygulamasının hematolojik ve biyokimyasal parametrelerde önemli değişikliklere neden olduğu ve tek doz uygulamalarda geçici şekillenen bu değişimlerin tekrarlı uygulamalarda risk oluşturabileceğinden dikkatli olunması gerektiği kanısına varıldı. 

Anahtar Kelimeler

• Artan doz
• Biyokimyasal
• Hematolojik
• Keçi
• Pentoksifilin

Kaynakça

1. Antunes SA, Teixeira MdCB, Júnior AG. Pentoxifylline effects on the resistant anemia to erythropoietin in hemodialysis patients. Rev. Bras. Hematol. Hemoter. 2008; 30(4): 303-308.
2. Carletto A, Biasi D, Bambara LM, Caramaschi P, Bonazzi ML, Lussignoli S, Andrioli G, Bellavite P.Studies of Skin-Window Exudate Human Neutrophils: Increased Resistance to Pentoxifylline of the Respiratory Burst in Primed Cells. Inflammation. 1997; 21(2): 191-203.
3. Cioboată R, Găman A,Traşcă D, Ungureanu A, Docea AO, Tomescu P, Gherghina F, Arsene AL, Badiu C, Tsatsakis AM, Spandidos DA, Drakoulis N, Călina D. Pharmacological management of non-alcoholic fatty liver disease: Atorvastatin versus pentoxifylline. Exp Ther Med. 2017; 13: 2375-2381.
4. Cooper A, Mikhail A, Lethbridge MW, Kemeny DM, Macdougall IC. Pentoxifylline Improves Hemoglobin Levels in Patients with Erythropoietin-resistant Anemia in Renal Failure. J Am Soc Nephrol. 2004; 15: 1877–1882.
5. Corum DD, Corum O, Er A, Uney K. Biochemical and hematological changes in response to single-ascendind doses of pentoxyfilline in sheep. “1th International Congress on Advances in Veterinary Sciences & Technicsis”, August, 25-29. 2016. Sarajevo, Bosnia and Herzegovina (Abstract).
6. Corum O, Corum DD, Atik O, Er A, Uney K. Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after intravenous administration of increasing doses to sheep. Am J Vet Res. 2019; 80(7): 702-708.
7. Corum O, Er A, Dik B, Eser H, Bahcivan E, Yazar E. Determination of the safety of tulathromycin in sheep. Eurasian J Vet Sci. 2015; 31(3): 152-157.
8. Corum O, Ozdemir O, Hitit M, Corum DD, Coskun D, Er A. Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats. Acta Sci Vet. 2018; 46(1): 1-7.

9. Coskun D, Canbar R, Korkmaz Y, Dik B, Er A, Yazar E. Danofloksasinin 8-hidroksi-2-deoksiguanozin düzeyine etkisinin belirlenmesi. Eurasian J Vet Sci. 2019; 35(4), 224-229.
10. Coskun D, Parlak K, Dik B, Faki HE, Bahcivan E, Yazar E, Er A. Effect of enrofloxacin on the joint fluid/blood oxidative status and organ damage markers. Annual Research & Review in Biology. 2018; 1-7.
11. De Boever S, Baert K, De Backer P, Croubels S. Pharmacokinetics and oral bioavailability of pentoxyfylline in broiler chickens. J Vet Pharmacol Ther. 2005 Dec; 28(6):575-80
12. El-Haggar SM, Mostafa TM. Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease. Hepatol Int. 2015; 9: 471–479.
13. Genoves P, Garcia D, Cejalvo D, Martin A, Zaragoza C, Toledo AH, Toledo-Pereyra LH, Lloris-Carsi JM. Pentoxifylline in Liver Ischemia and Reperfusion. J Investig Surg. 2014; 27: 114–124.
14. Golbasi I, Turkay C, Timuragaoglu A, Ozdem SS, Belgi A, Akbas H, Bayezid O. The effect of pentoxifylline on haemolysis in patients with double cardiac prosthetic valves. Acta Cardiol. 2003; 58(5): 379-383.
15. Jalili C, Moradi D, Roshankhah S, Salahshoor MR. Effect of pentoxifylline on kidney damage induced by nitrosamine inmale rats. Res Pharm Sci. 2019; 14(1): 64-73.
16. Kim YK, Choi TR, Kwon CH, Kim JH, Woo JS, Jung JS. Beneficial Effect of Pentoxifylline on Cisplatin-Induced Acute Renal Failure in Rabbits. Renal Failure. 2003; 25(6): 909–922.
17. Liska DA, Akucewich LH, Marsella R, Maxwell LK, Barbara JE, Cole CA. Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after oral and intravenous administration of pentoxifylline to healthy adult horses. Am J Vet Res. 2006; 67(9): 1621-1627.
18. Mohammadzadeh A, Heidari M, Soltanghoraee H, Jeddi-Tehrani M, Novin MG, Akhondi MMA, Zeraati H, Mohammadzadeh F. Evaluation of the effect of pentoxifylline on white blood cell count in serum and peritoneal fluid in female rats with endometriosis. J Obstet Gynaecol Res. 2008; 34(3): 307–313.
19. Mohammed SA, RazzaqueMA, Omar AE, Albert S, Al-Gallaf WM. Biochemical and hematological profile of different breeds of goat maintained under intensive production system. AFR J Biotechnol. 2016; 15(24), 1253-1257.
20. Narin F, Demir F, Akgün H, Baykan A, Üzüm K, Kuzugüden S, Köklü E. Doksorubisin ile oluşturulmuş deneysel kardiyotoksisite ve kardiyotoksisite üzerine pentoksifilin etkisi. Türk Kardiyol Dern Arş. 2004; 32(5): 279–287.
21. Njidda AA, Hassan IT, Olatunji EA. Haematological and biochemical parameters of goats of semi arid environment fed on natural grazing rangeland of northern Nigeria. IOSR JAVS. 2013; 3(2), 01-08.
22. Radostits OM, Gay C, Hinchcliff KW, Constable PD. Veterinary Medicine E-Book: A textbook of the diseases of cattle, horses, sheep, pigs and goats. Elsevier Health Sciences. 2006; pp. 39-124.
23. Rees CA, Boothe DM, Boeckh A, Wilkie S, Esparza T, Green R. Dosing regimen and hematologic effects of pentoxifylline and its active metabolites in normal dogs. Vet Ther. 2003; 4(2): 188-196.
24. Samlaska CP, Winfield EA. Pentoxifylline. J Am Aca Dermatol. 1994; 30(4), 603-621.
25. Sezik M, Köker A, Özmen Ö, Halıgür M, Kaşıkcı D, Aydoğan A, Özatik O. Antenatal pentoxifylline therapy to prevent endotoxin induced fetal injury in the preterm goat model. Turk J Obstet Gynecol. 2020; 17: 259-269.
26. Shahbazian H, Ghorbani A, Zafar-Mohtashami A, Balali A, AleAli A, Lashkarara GR. Administration of pentoxifylline to improve anemia of hemodialysis patients. J Renal Inj Prev. 2017; 6(1): 61-64.
27. Sykes JE, Papich MG. Antiviral and immunomodulatory drugs. Canine and feline infectious diseases. 2014; 54.
28. Tuncer İ, Uygan İ, Dülger H, Türkdoğan K, Şekeroğlu R, Kösem M. The comparative effects of pentoxifylline and ursodeoxycholic acid on IL-1β, Il-6, Il-8 and TNF-α levels in nonalcoholic fatty liver. East J Med. 2003; 8(2): 27-32.
29. Uney K, Tras B, Corum O, Yildiz R, Maden M. Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following intravenous administration in cattle. Trop Anim Health Prod. 2019; 51(2): 435-441.
30. Van Miert ASJPAM, Van Duin CTM, Wensing T. Effects of pentoxifylline and polymyxin B on the acute phase response to Escherichia coli endotoxin in dwarf goats. J Vet Pharmacol Ther. 1997; 20(1), 61-68.
31. Wadie W, Abdel-Razek NS, Salem HA. Phosphodiesterase (1, 3 & 5) inhibitors attenuate diclofenac-induced acute kidney toxicity in rats. Life Sci. 2021; 277, 119506.
32. Yang KH, Lee MG. Effects of endotoxin derived from Escherichia coli lipopolysaccharide on the pharmacokinetics of drugs. Arch Pharm Res. 2008; 31, 1073-1086.