Effect of tetracycline administration on serum amylase activity in calves

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Effect of tetracycline administration on serumamylase activity in calves Bamdad Zendehbad1*, Adeleh Alipour2 and Hussein Zendehbad3 Tetracycline and related compounds are used extensively as broad spectrum antibiotics in the treatment ofbacterial infections in ruminants. Tetracycline may cause acute pancreatitis which may result in increased serumamylase activity. However, it has been shown that administration of oxytetracycline in human results in decreaseserum amylase activity. In this study changes in serum amylase activity were measured in 20 clinically healthy calvesfollowing intravenous injection of oxytetracycline hydrochloride at 10 mg/kg of body weight. Blood samples werecollected at 30, 60, and 120 minutes after oxytetracycline injection. Serum amylase activity was measured using theamyloclastic assay. The activity of serum amylase was increased significantly (P < 0.05) at 30 (40.5%), 60 (35.1%), and120 (39.3%) minutes after oxytetracycline hydrochloride administration. To the authors’ knowledge this is the firststudy on the acute effect of tetracycline administration on serum amylase activity in calves.
Tetracycline and related compounds are used exten- Amylase is a cytoplasmic enzyme that catalyzes the hy- sively as broad spectrum antibiotics in the treatment of drolysis of complex starches (Stockham and Scott ).
bacterial infections in ruminants. Several studies have Acute pancreatitis is the most common cause of increased shown that tetracycline may cause acute pancreatitis in serum amylase activity (hyperamylasemia) and therefore, human (Nicolau et al. Bernejee et al. Torosis serum amylase measurement is commonly used as a diag- and Vender Elmore and Rogge Bourke et al.
nostic tool for the diagnosis of acute pancreatitis. Serum It has also been suggested that oxytetracycline in- amylase has been in use as a diagnostic enzyme longer hibits protein synthesis in the pancreatic exocrine than any other enzymes (Hoffmann and Solter .
(Fleischer Fleischer and specifically amylase Several isoenzymes of amylase have been identified in synthesis and secretion (Tucker and Webster cattle (Gebicke-Härter and Geldermann The isoen- Tetracyclines are commonly used in cattle; however, zymes are found in a wide variety of tissues (Gebicke- the effect of tetracycline administration on serum amyl- Härter and Geldermann . Pancreatic amylase activity ase activity in cattle is unknown. The purpose of this in bovine is known to be very slow in vivo (Kay Karr study was to assess changes in serum amylase activity et al. , probably due to special digestive conditions in following administration of oxytetracycline to clinically the ruminant; however, it is very active in the newborn calf (Siddons ). In contrary to human, bovine do not havesalivary α-amylase (Stockham and Scott ). Amylase isalso produced in the small intestines and liver (Hoffmann and Solter . Intestinal amylase has not been shown A total of 20 clinically healthy Holstein calves (2–4 to increase total serum amylase activity (Stockham and months old) were randomly selected from a commer- cial dairy herd in Mashhad, Iran. Health records weremaintained on all calves by the dairymen and observa-tions relating to disease were made by a production 1Department of Physiology, Faculty of Specialized Veterinary Science, Blood samples were collected before administration of Research and Science Branch, Islamic Azad University, Tehran, IranFull list of author information is available at the end of the article oxytetracycline (predose T0). Oxytetracycline hydrochloride 2013 Zendehbad et al.; licensee Springer. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.
Zendehbad et al. SpringerPlus 2013, 2:330 http://www.springerplus.com/content/2/1/330 Table 1 Serum amylase activity before and after Fisher’s exact two-tailed test analysis was performed and intravenous administration of oxytetracycline differences were considered significant at values of P < 0.05.
hydrochloride in 15 clinically healthy Holstein calves The present study was approved and conducted in ac- cordance with the recommendations of the Animal Care and Use Ethics Committee of the College of Veterinary Medicine, Islamic Azad University-Shahrekord Branch.
The mean and standard deviation (SD) of serum amylase activity in 15 calves measured at 30, 60, and 120 min *Data presented as mean ± standard deviation (SD).
a,b after oxytetracycline injection are presented in Table Values with no common superscript are significantly different (P < 0.05).
and Figure In this study, the activity of serum amylase (10%; Razak Lab, Tehran, Iran) was intravenously adminis- was significantly (P < 0.05) increased in all animals at 30 tered at 10 mg/kg of body weight. Then, blood samples (40.5%), 60 (35.1%), and 120 (39.3%) minutes after oxy- were collected at 30, 60, and 120 min after oxytetracycline tetracycline hydrochloride administration. No statisti- injection. Blood was drawn directly to the serum clot tube cally significant differences were present in serum using a single jugular venepuncture and a Vacutainer nee- amylase activity measured at 30, 60, and 120 min after dle. The samples were immediately transported to the Clin- oxytetracycline hydrochloride administration.
ical Pathology laboratory in a cooler with ice packs andwere processed within an hour of blood collection. The samples were centrifuged at 2000 g for 20 min at 4 C, and Tetracyclines are broad-spectrum antibiotics, widely used serum was stored at −20°C until analysis. Five samples with for both prevention and treatment of bacterial infections.
visual hemolysis were excluded from the study. No clinical In cattle they are also used for growth promotion. Tetracy- signs of adverse effects were noted during the experiment clines have long been implicated as a causative agent in and the calves were returned to their home pens.
acute pancreatitis (Badalov et al. Forsmark and Serum amylase activity was measured using the amy- Baillie ; Nicolau et al. Torosis and Vender loclastic assay as described previously (Stockham and Elmore and Rogge ; Mallory and Kern ). In- Scott ). An automated chemistry analyzer (VITALAB creased serum amylase activity is used as a reliable bio- Selectra 2, Merck, Germany) and a commercially available marker for the diagnosis of acute pancreatitis. However, kit (Pars-Azmoon Co., Iran) were used to measure amyl- several studies have shown that administration of oxyte- ase activity. All serum samples were tested in duplicate.
tracycline in human results in decrease serum amylase ac- For statistical analysis, data were transferred to a tivity (Fleischer Lorenzo et al. have reported Microsoft Excel spreadsheet (Microsoft Corp., Redmond, that treatment with oxytetracycline results in low amylase WA, USA). Using SPSS 16.0 statistical software (SPSS activity in pancreatic tissue and duodenal fluids. In vitro Inc., Chicago, IL, USA), a Pearson chi-square test and studies have shown that tetracycline has a substantial alpha Figure 1 Serum amylase activity before (T0) and at 30 (T1), 60 (T2), and 120 (T3) minutes after intravenous administration ofoxytetracycline hydrochloride in 15 clinically healthy Holstein calves.
Zendehbad et al. SpringerPlus 2013, 2:330 http://www.springerplus.com/content/2/1/330 amylase inhibitory activity in a dose dependent fashion Received: 19 November 2012 Accepted: 16 July 2013 (Hamdan II et al. In a recent study in rats, it has been shown that the content of amylase in pancreas signifi- cantly decreases in the animals given 50 or 200 mg kg(−1) Asha KK, Sankar TV, Viswanathan Nair PG (2007) Effect of tetracycline on pancreas and liver function of adult male albino rats. J Pharm Pharmacol59:1241–1248 An amylase level more than three times above upper Badalov N, Baradarian R, Iswara K, Li J, Steinberg W, Tenner S (2007) reference interval is highly specific for pancreatitis Drug-induced acute pancreatitis: an evidence-based review. Clin (Cappell In this study amylase activity was mildly Bernejee AK, Patel KJ, Grainger SL (1989) Drug-induced acute pancreatitis. Med to moderately increased (up to 40.5%) after administra- tion of oxytetracycline hydrochloride. It has been shown Bourke JB, Mead GM, McIllmurray MB, Longman MJS (1978) Drug-associated that drug-induced pancreatitis tends to be mild and self primary acute pancreatitis. Lancet 1:706–708 Burrows GE, Barto PB, Martin B (1987) Comparative pharmacokinetics of limited (Cappell Serum amylase level increases gentamicin, neomycin and oxytetracycline in newborn calves. J Vet from leakage from the inflamed pancreas into the blood- stream. Amylase is believed to rise within the first hours Cappell MS (2008) Acute pancreatitis: etiology, clinical presentation, diagnosis, after the onset of pancreatitis and return to the normal Clavien PA, Robert J, Meyer P, Borst F, Hauser H, Herrmann F, Dunand V, Rohner A (1989) Acute pancreatitis and normoamylasemia. Not an uncommon In the present study oxytetracycline hydrochloride was Elmore MF, Rogge JD (1981) Tetracycline-induced pancreatitis. Gastroenterology intravenously administered at 10 mg/kg of body weight.
The half-life of elimination of oxytetracycline adminis- Fleischer K (1976) Exocrine pancreatic function in man after treatment with tered at this dosage in calves has been reported to be 6.4 ± oxytetracycline and chloramphenicol. Digestion 14:108–116 Fleischer K (1974) Effect of oxytetracycline and chloramphenicol on the exocrine 1.3 hour at 6 weeks of age (Burrows et al. ). Oxytetra- pancreatic function in the rat. Digestion 11:382–391 cycline is mostly excreted by the kidney (85-86%) and Forsmark CE, Baillie J (2007) AGA Institute clinical practice and economics mainly through glomerular filtration (Nouws et al. committee: AGA Institute technical review on acute pancreatitis.
Gastroenterology 132:2022–2044 Amylase is catabolized by the kidneys and liver. Re- Gebicke-Härter PJ, Geldermann H (1977) Blood serum and pancreatic amylases in duced amylase clearance may lead to elevation of serum cattle. Some biochemical parameters. Int J Biochem 8:677–683 amylase level, especially in cases of renal insufficiency.
Hamdan II, Afifi F, Taha MO (2004) In vitro alpha amylase inhibitory effect of some clinically-used drugs. Pharmazie 59:799–801 In the present study kidney function was not assessed; Hoffmann WE, Solter PF (2008) Diagnostic enzymology of domestic animals. In: however, the animals did not show clinical signs of acute Kaneko JJ, Harvey JW, Bruss ML (eds) Clinical biochemistry of domestic animals, 6th edn. Academic Press, San Diego, pp 351–378 Karr MR, Little CO, Mitchell GE Jr (1966) Starch disappearance from different segments of the digestive tract of steers. J Anim Sci 25:652–654 Kay RNB (1969) Digestion of protein in the intestines of adult ruminants. Proc In conclusion, the results of this study showed that Lorenzo C, del Olmo Martinez ML, Pastor L, Almaraz A, Belmonte A, Caro-Patón A serum amylase activity was significantly (P < 0.05) in- (1999) Effects of oxytetracycline on the rat exocrine pancreas. Int J Pancreatol creased 30 minutes after administration of tetracycline.
Mallory A, Kern F (1980) Drug-induced acute pancreatitis. A critical review.
To the authors’ knowledge this is the first study on the acute effect of tetracycline administration on serum Nicolau DP, Megedoht DE, Kline JJ (1991) Tetracycline-induced pancreatitis.
amylase activity in calves. Further studies will be re- Nouws JF, Vree TB, Termond E, Lohuis J, van Lith P, Binkhorst GJ, Breukink HJ quired to confirm the preliminary observations of the (1985) Pharmacokinetics and renal clearance of oxytetracycline after intravenous and intramuscular administration to dairy cows. Vet Q 7:296–305 Siddons RC (1968) Carbohydrase activities in the bovine digestive tract. Biochem J The authors declare that they have no competing interests.
Stockham SL, Scott MA (2008) Enzymes. In: Stockham SL, Scott MA (eds) Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, Ames, IA,p 663 Torosis J, Vender R (1987) Tetracycline-induced pancreatitis. J Clin Gastroenterol BZ carried out the blood sampling and analysis and drafted the manuscript.
AA carried out the statistical analysis. HZ participated in writing the Tucker PC, Webster PD (1972) Effects of tetracycline on pancreatic protein manuscript. All authors read and approved the final manuscript.
synthesis and secretion in pigeons. Am J Dig Dis 17:675–682 The authors would like to thank Drs. Hajhameshi and Ameri for their Cite this article as: Zendehbad et al.: Effect of tetracycline valuable contribution to this study.
administration on serum amylase activity in calves. SpringerPlus2013 2:330.
Author details1Department of Physiology, Faculty of Specialized Veterinary Science,Research and Science Branch, Islamic Azad University, Tehran, Iran.
2Department of Statistic, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad, Iran. 3Department of Biotechnology, Indianacademy, centre for research & post graduate studies, Bangalore, India.

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