Indian Journal of Animal Research

  • Chief EditorK.M.L. Pathak

  • Print ISSN 0367-6722

  • Online ISSN 0976-0555

  • NAAS Rating 6.50

  • SJR 0.263

  • Impact Factor 0.5 (2023)

Frequency :
Monthly (January, February, March, April, May, June, July, August, September, October, November and December)
Indexing Services :
Science Citation Index Expanded, BIOSIS Preview, ISI Citation Index, Biological Abstracts, Scopus, AGRICOLA, Google Scholar, CrossRef, CAB Abstracting Journals, Chemical Abstracts, Indian Science Abstracts, EBSCO Indexing Services, Index Copernicus
Submit

Full Research Article

Comparison of Asymmetric Dimethyl Arginine and Oxidative Stress Parameters in Obese Dogs and Dogs with Clinically Normal Body Condition Based on Routine Hemogram and Serum Biochemicals

H. Cihan1,*, M. Tunca2
1Department of Internal Medicine, Bursa Uludag University, Faculty of Veterinary Medicine, Bursa, Turkiye.
2Department of Veterinary Internal Medicine, Bursa Uludag University, Institute of Health Science, Bursa, Turkiye.

ABSTRACT

Background: Obesity, which has recently created many problems in humans and animals, is stated as being above 15-20% of normal body weight. This condition is commonly classified using body condition scoring in dogs. This study compared oxidative stress (malondialdehyde, catalase, superoxide dismutase), asymmetric dimethylarginine (ADMA), routine hemograms and biochemicals in obese dogs and dogs with normal body conditions. 

Methods: Blood samples were taken from 20 normal body condition and 20 obese dogs. ADMA, oxidative stress and routine hematologic and biochemical parameters were evaluated. 

Result: Platelet count (p = 0.009), blood urea nitrogen (p <0.001), cholesterol (p = 0.006), ADMA (p <0.05) and malondialdehyde (p<0.001) were statistically high, while superoxide dismutase and catalase (p <0.001 and p <0.001, respectively) were statistically low in the obese group than the normal body condition group. As a result, we think the interpretation of the indicated biomarkers may help evaluate obesity and related pathologies in dogs, monitor treatment, or help prevent potential problems associated with obesity.

INTRODUCTION

Obesity is dogs’ most common and vital problem (Barko et al., 2017). More than 30 per cent of dogs in wealthy countries are overweight or obese, with rates expected to range from 33% to 58%, according to research data. In animals, obesity may be associated with many factors, such as genetics, excessive consumption of high-energy foods and a sedentary lifestyle (Kawauchi et al., 2017). The usability of diagnosis and treatment tools in preventing and treating obesity is thought-provoking (Barko et al., 2017). Some studies have evaluated the awareness of pet owners regarding care and feeding. It has been determined that the owners of obese animals are overweight and struggle with their body weight (Candellone et al., 2017).
       
Asymmetric dimethyl arginine (ADMA) has increased in adipose tissue and serum levels in obese people due to primary or underlying causes of obesity (Holguin and Fitzpatrick, 2010). ADMA is an arginine-like amino acid found in plasma, urine and tissues. ADMA, naturally formed by the methylation of arginine residues in proteins, is an endogenous nitric oxide (NO) synthetase inhibitor and was excreted in the urine as methylated arginine (Aydin et al., 2013). In the following years, methylated arginines were detected in the immune system cells and neurons of animals and the endothelial cells of humans (Surmeli, 2013). ADMA is in the group of methylarginines. Methylarginines are found in ADMA, monomethyl-L-arginine (L-NMMA) and symmetrical dimethyl arginine (SDMA). Only L-NMMA and ADMA are nitric oxide synthetase (NOS) inhibitors. The plasma ADMA level is ten times higher than the L-NMMA level. ADMA is the major inhibitor of NO biosynthesis.
       
Oxidative stress also increases ADMA in the blood by decreasing the level of DDHA (Nabity et al., 2015). Oxidative stress, disrupting the balance between the oxidant and the antioxidant systems toward the oxidant system, is the formation of cellular damage in the organism because of lipid peroxidation and the release of free radical/reactive oxygen products. ADMA levels are high in many diseases that increase oxidative stress (Aydin et al., 2013). When the organism’s defense mechanisms (antioxidant mechanisms) against oxidative stress are insufficient, oxidative damage develops in the cells and functions are disrupted significantly. This situation is critically important in the pathogenesis of many diseases and the severity of the disease increases. The enzyme systems in the cells are primarily effective in the defense system against free radicals. Catalase (CAT), glutathione peroxidase (GSH-Px) and Superoxide dismutase (SOD) are the most important enzymatic antioxidants that prevent the accumulation of free radicals and the initiation of lipid peroxidation (Isiklar and Mutaf, 2010).
       
Malondialdehyde (MDA), a parameter of oxidative stress and one of the most critical indicators of lipid peroxidation, causes changes in membrane properties such as enzyme activity, ion transport and aggregation of cell surface components (Tabakoglu and Durgut, 2013). Obesity can be detected together with disease states, including hyperlipidemia, hypertension, insulin resistance, diabetes mellitus and hypothyroidism. Each disease listed alone can increase the oxidative stress load, so in obesity cases, oxidative stress parameters may increase in the serum either with these diseases or alone (with the formation of fat accumulation) (Tvarijonaviciute et al., 2012). It has been reported that obesity in dogs is also associated with a decrease in plasma antioxidant levels (Tvarijonaviciute et al., 2012).
       
Although it is thought that the underlying cause of oxidative stress in animals is the disorder in metabolic functions (Webb and Falkowski, 2009; Zoran, 2010), there are very few studies on obese dogs on this subject (Tvarijonaviciute et al., 2012).
               
Therefore, this study aimed to evaluate whether ADMA and oxidative stress parameters are diagnostic and prognostic biomarkers in addition to routine hematologic and biochemical markers in obese dogs.

MATERIALS AND METHODS

Study materials
 
The experiment was conducted between 2017-2018 at the Internal Medicine Department of the Faculty of Veterinary Medicine, Bursa Uludag University, Turkiye. The study material consisted of 20 clinically healthy dogs with normal body condition and 20 obese dogs brought to our Animal Teaching Hospital. The dogs that formed the study were between 3 and 5 years old. Dogs that were clinically healthy and did not receive any treatment were included in the study after their routine clinical examinations were completed, as stated in the previous study (Cihan and Tural, 2019). The study group consisted of regularly vaccinated dogs and antiparasitic applications were made. All dogs were fed quality dry commercial food once daily without any treatment and/or supplementation, consuming tap water. The owners’ information about their feeding interval starts from one year old.
       
Dogs with a score of 3 (normal body condition) or 5 (obese) according to the clinical definition of BCS of the American Animal Hospitals Association (AAHA) according to a 5-point score were added to the study groups. Among these dogs, ten female and ten male dogs were in the group with BCS 3 and nine female and 11 male dogs had a score of 5.
 
Sample collection and methodology
 
For hemogram analysis from dogs in the study, blood samples were taken into 2 ml sterile vacuum tubes containing ethylenediamine tetraacetic acid (EDTA) three to four hours after feeding. Hemogram analysis was performed using an Abacus Junior Vet (3240 Whipple Road Union City, CA 94587, USA) device in the Bursa Uludag University Faculty of Veterinary Medicine, Department of Internal Medicine laboratory.
       
For biochemical analysis [alanine aminotransferase (ALT), alkaline phosphatase (ALP), amylase (AMY), blood urea nitrogen (BUN), total bilirubin (TBIL), phosphorus (PHOS), glucose (GLU), creatinine (CRE), sodium (Na), potassium (K), globulin (GLOB), total protein (TP), cholesterol (CHOL), asymmetric dimethyl arginine (ADMA), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)], blood was taken into 9 ml sterile vacuum serum tubes. Samples of the study material were collected between February and December 2017. The blood samples were centrifuged after coagulation at 1200 rpm for 10 min using Elektro-mag Laboratory Centrifuge M4812P (Elektro-mag Lab. Alt. San. Tic. A.Þ. Ýkitelli O.S.B. Demirciler Sitesi B7/153 Ýkitelli, Istanbul, Turkiye). Then, the separated serum samples were transferred into capped cryo tubes and WISD Ultra Low-Temperature Freezer SWUF-300 at -80°C. (DAIHAN Scientific Co., Ltd., Korea) instrument until the time of analysis. Biochemical analyses were performed in the Central Laboratory of our faculty; VetScan Abaxis Chompherensive Diagnostic Profile (3240 Whipple Road Union City CA 94587, USA) and Reflotron Plus Clinical Chemistry Analyser (Roche Diagnostics GmBh Mannheim, Germany) device were used. ADMA, MDA, SOD and CAT were analyzed using the enzyme-linked immunosorbent assay (ELISA) method using the ELx808 Absorbance Microplate Reader-BioTek (BioTek Instruments, Inc., Winooski, VT, USA).
 
Ethical approval
 
This study was approved by Bursa Uludag University Animal Experiments Local Ethics Committee with the decision numbered 2016-08/01 on 07.06.2016.
 
Informed consent
 
Informed consent has been obtained for client-owned animals included in this study.
 
Statistical analysis
 
The findings obtained from the cases mentioned in the study were evaluated with Student’s t, Mann–Whitney U, Pearson and Spearman correlation tests in the SigmaPlot 14 statistical program. Those with a probability value (p) of 0.05 or were statistically significant.

RESULTS AND DISCUSSION

Hematologic and biochemical profiles
 
Platelet count was significantly higher in the obese dogs than in normal body condition group (355.2±22.568; 245.2±28.723 109/L, p=0.009, respectively), as shown in Table 1. Also, CHOL (248.450±21.058 vs. 176.750±8.314 mg/dL, p=0.006), BUN (17.950±2.139 vs. 10.500±0.925 mg/dL, p<0.001), ADMA (1.179±0.107 vs. 0.759±0.109 µmol/L, p<0.001) and MDA (198.250±4.070 vs. 125.100±3.797 pg/mL, p<0.001) were significantly higher; SOD (474.400±14.377 vs. 565.350±5.987 pg/mL, p<0.001) and CAT (0.937±0.010 vs. 1.691±0.035 pg/mL, p<0.001) values were significantly lower in the obese than in dogs with normal body condition, as shown in Table 2.
 

Table 1: Comparison of blood parameters of dogs with normal body condition and obese groups.


 

Table 2: Pairwise comparisons of serum biochemical parameters between normal body condition and obese dogs.


       
It has been reported that obesity is a low-grade inflammatory condition (Chmelar et al., 2013). In a study (Rafaj et al., 2016), the hypothesis of finding high WBC, RBC, HCT and HGB values in subjects in the obese group was proposed. The researchers determined no difference between obese dogs and those with normal body condition in terms of the specified parameters. Our study found WBC and NEU values to be higher in the obese group, although not statistically. Radakovich et al., (2017) obtained results from their study in parallel with ours and researchers based this result on the response to stress and low-grade inflammatory reaction. The short lifespan of the NEU indicates continued low-grade chronic infection and immune system activation in overweight and obese dogs. Also, higher PLT counts found in the obese group in the present study might be secondary to chronic inflammation. In addition to this inflammatory condition, it has been reported that one of the possible reasons for the high NEU may be that the subjects in the obese and overweight groups are hypercholesterolemic. Based on this situation, this study’s increased total cholesterol amount increases the NEU level, as reported in a study (Yvan-Charvet et al., 2008). In our research, the CHOL level of dogs in the obese group was higher and hypercholesterolemia and/or low-grade inflammatory reaction might cause higher NEU levels in the obese group, as indicated in the previous studies. Additionally, high ADMA levels have been found in humans and dogs with hypercholesterolemia and inflammatory diseases (Gori et al., 2020; Korkmaz et al., 2021). In our study, ADMA levels were higher in the obese group than in the normal body condition group (1.179±0.107, 0.759±0.109 µmol/L, respectively) (p<0.05). It may indicate an inflammatory response and the high levels of neutrophils support our argument. 
       
Many studies have detected changes in some biochemical parameters in obesity and related diseases. Studies on obese people and dogs have reported a positive relationship between obesity and ADMA (Marliss et al., 2006; Kocak et al., 2011; Huang et al., 2017; Cihan and Tural, 2019). In our study, ADMA levels in obese dogs were significantly higher. However, as a result of a search in scientific article resources, no publications related to obesity and ADMA were found in dogs, except in our previous study (Cihan and Tural, 2019). In an experimental study, mice were given a high-fat diet to induce obesity and their ADMA levels were evaluated (Li et al., 2017). The DDAH enzyme, which is involved in ADMA metabolism and expressed in the liver, is decreased due to fatty liver. Therefore, fatty liver has been reported to cause an increase in ADMA levels (Li et al., 2017).
       
SOD and CAT are important antioxidant enzymes that are activated to act against oxidative stress in tissues and prevent the accumulation of free radicals and the initiation of lipid peroxidation (Isiklar and Mutaf, 2010; Torkanlou et al., 2016). In a study, it was determined that the level of SOD in obese people was lower than in the control group (Torkanlou et al., 2016). Moreover, in a study conducted on mice, SOD and CAT values were significantly lower in obese mice compared to the control group (Manna and Jain, 2015). In another study on cats, no change was found in the antioxidant activity of CAT and SOD during the development of obesity (Hoenig et al., 2013). To the authors’ knowledge, there are no studies on SOD and CAT antioxidant activity in obese dogs. However, antioxidant mechanisms are stimulated in the formation process of obesity and high levels of antioxidants can be determined in the metabolism at the beginning. In late obesity, a decrease in antioxidant levels indicates uncompensated oxidative stress (Sabitha et al., 2014). In our study, serum SOD and CAT levels were found to be significantly lower in the obese group. Considering the studies above, we can evaluate the reason for the decrease in SOD and CAT levels in the obese group in our study as a response to the long-term obesity of these dogs.
       
Since it is costly and difficult to determine the increase in ROS, MDA measurement is made; therefore, oxidative stress can be determined (Holguin and Fitzpatrick, 2010). MDA is a product of lipid peroxidation reaction and MDA levels increase in parallel with increased oxidative stress in obesity (Holguin and Fitzpatrick, 2010; Tabakoglu and Durgut, 2013; Amirkhizi et al., 2010). In a study conducted on dogs with hyperlipidemia, serum MDA levels were measured before and after treatment and it was determined that the MDA level decreased after treatment (Li et al., 2014). In another study by Kawasumi et al., (2018), MDA levels were found to increase, although not statistically, in obese dogs fed high-fat diets for a long period. In our study, serum MDA levels were significantly higher in obese dogs than in dogs with normal body condition (p<0.001). With the formation of fat accumulation, obesity can alone increase oxidative stress in dogs, resulting in an increase in biomarker levels such as MDA. Chronic postprandial change may affect oxidative stress and ADMA metabolism (Mah et al., 2011). This study suggested that increases in ADMA and MDA values might also be associated with chronic postprandial increase.
       
In vivo and in vitro studies have reported that bilirubin is an antioxidant that can physiologically inhibit lipid and lipoprotein oxidation (Tomaro and Batlle, 2002; Liu et al., 2006). It is thought that bilirubin constitutes one-tenth of all antioxidant effects in healthy adult humans and bilirubin levels are negatively correlated with serum oxidative biomarker levels (Kalousova et al., 2005; Demir et al., 2013). It has been reported that antioxidant levels increase due to increased oxidative stress during the development of obesity (Sabitha et al., 2014). Previous studies determined higher bilirubin levels in obese or hyperlipidemic dogs and humans (Yamka et al., 2006; Li et al., 2014; Piantedosi et al., 2016; Bosco et al., 2018). The bilirubin level determined in obesity increases to reduce the increasing oxidative stress load in metabolism and creates an antioxidant effect (Zhong et al., 2017). In our study, the serum total bilirubin level was higher in obese dogs compared to dogs with normal body condition, but it was within the reference range in both groups. Thus, it was concluded that bilirubin could not have a negative effect on MDA, which is a secondary product produced during lipid peroxidation and is considered a biomarker for oxidative stress due to its insufficient antioxidant effect.
               
Some studies have reported high serum BUN values in obese dogs (Tribuddharatana et al., 2011; Kawasumi et al., 2018). The reasons for the increased serum BUN levels in obesity can be counted as an increased excretory load of the kidney, increased renal sodium retention and lipotoxicity (Bagby, 2014). Our study determined that obese dogs had higher serum BUN levels than those with normal body conditions. The fact that the serum BUN values we obtained were in the reference range showed parallelism with the study by Abinaya et al., (2018). These researchers evaluated age-related biochemical parameters in obese dogs and found serum BUN values in the reference range of all obese dogs. In addition, the presented study found a positive correlation between BUN and MDA levels. This situation raises the opinion that it may explain the possible increases in BUN levels with the increase in oxidative stress.

CONCLUSION

In conclusion, serum ADMA levels in obese dogs were higher than normal body condition group. This difference supports that ADMA may be a diagnostic biomarker in obese dogs. Statistically significant correlations between bilirubin, BUN and MDA will shed light on future studies. Examining routine hemograms and biochemicals with oxidative stress parameters and ADMA in evaluating the health status of obese dogs will provide us with prognostically essential data. However, it may be helpful to assess these parameters in more dogs with optimum conditions, which are obese and in normal body condition. We believe this study will form the basis for future studies on obesity in dogs.

ACKNOWLEDGEMENT

The present study was implemented with the support of Bursa Uludag University Scientific Research Project Unit Number: (DDP (V)-2016/10).

CONFLICT OF INTEREST

None.

REFERENCES


  1. Abinaya, A., Karu, P., Kunakaran, R., Cecilia, J., Senthil, N.R., Vairamuthu, S. (2018). Influence of age on blood biochemical  profile of obese dogs. International Journal of Chemical Studies. 6(3): 991-993. 

  2. Amirkhizi, F., Siassi, F., Minaie, S., Djalali, M., Rahimi A., Chamari, M. (2010). Is obesity associated with increased plasma lipid peroxidation and oxidative stress in women? Arya Atherosclerosis. 2(4): 189-192.

  3. Aydin, M., Erdogmus, F., Armutcu F, Yigitoglu, M.R. (2013). Metabolism  of asymmetric dimethyl arginine (ADMA). International Journal of Basic and Clinical Medicine. 1: 61-66. 

  4. Bagby, S.P. (2014). Obesity-initiated metabolic syndrome and the kidney: A recipe for chronic kidney disease? Journal of the American Society of Nephrology. 15: 2775-2791.

  5. Barko, P.C., Mcmichael, M.A., Swanson K.S., Williams, D.A. (2017). The gastrointestinal microbiome: A review. Journal of Veterinary Internal Medicine. 32(1): 9-25.

  6. Bosco, A.M., Almeida, B.F.M., Valadares, T.C., Baptistiolli, L., Hoffmann, D.J., Pereira, A.A.F., Lima V.M.F., Ciarlini, P.C. (2018). Preactivation of neutrophils and systemic oxidative  stress in dogs with hyperleptinemia. Veterinary Immunology  and Immunopathology. 202: 18-24. 

  7. Candellone, A., Morgan, D., Buttignol S., Meineri, G. (2017). Leaner, healthier, happier together-A family-centred approach to weight loss with the overweight dog and her caregivers. Veterinary Sciences. 4(3): 41. doi: 10.3390/vetsci4030041.

  8. Chmelar, J., Chung K.J., Chavakis, T. (2013). The role of innate immune cells in obese adipose tissue inflammation and development of insulin resistance. Journal of Thrombosis and Haemostasis. 109(3): 399-406. 

  9. Cihan, H. and Tural, M. (2019). Assessment of asymmetric dimethyl arginine, cardiac troponin I, thyroxine, cholesterol and triglyceride levels in obese dogs and dogs with normal body condition. Turkish Journal of Veterinary and Animal Sciences. 43(2): 271-275.

  10. Demir, M., Demir C., Cosar, S. (2013). The relationship between serum bilirubin concentration and coronary slow flow. Therapeutic Advences in Cardiovascular Diseases. 7(6): 316-321. 

  11. Gori, E., Pierini, A., Lippi, I., Meucci, V., Perondi, F., Marchetti, V. (2020). Evaluation of asymmetric dimethylarginine as an inflammatory and prognostic marker in dogs with acute pancreatitis. Journal of Veterinary Internal Medicine. 34(3): 1144-1149.

  12. Hoenig, M., Pach, N., Thomaseth, K., Le, A., Schaeffer, D., Ferguson, D.C. (2013). Cats differ from other species in their cytokine  and antioxidant enzyme response when developing obesity. Obesity (Silver Spring, Md.). 21(9): E407-E414. 

  13. Holguin, F. and Fitzpatrick, A. (2010). Obesity, asthma and oxidative stress. Journal of Applied Physiology. 108: 754-759. 

  14. Huang, F., Del-Río-Navarro, B.E., Torres-Alcántara, S., Pérez- Ontiveros, J.A., Ruiz-Bedolla, E., Saucedo-Ramírez, O.J., Villafaña, S., Sánchez Muñoz, F., Bravo G., Hong, E. (2017). Adipokines, asymmetrical dimethylarginine and pulmonary function in adolescents with asthma and obesity. Journal of Asthma. 54(2): 153-161.

  15. Isiklar, O.O. and Mutaf, I. (2010). Asymmetric dimethyl arginine and its clinical significance (Asimetrik dimetilarginin ve klinik önemi). Turkish Journal of Biochemistry. 8(2): 75-89.

  16. Kalousova, M., Novotny, L., Zima, T., Braun M., Vítek, L. (2005). Decreased levels of advanced glycation end-products in patients with Gilbert syndrome. Cellular and Molecular Biology. 51(4): 387-392. 

  17. Kawasumi, K., Murai, T., Mizorogi, T., Okada, Y., Yamamoto, I., Suruga, K., Kadokura K., Arai, T. (2018). Changes in plasma metabolites concentrations in obese dogs supplemented with antioxidant compound. Frontiers in Nutrition. 7(5): 74. doi: 10.3389/fnut.2018.00074.

  18. Kawauchi, I.M., Jeremias, J.T., Takeara, P., De Souza, D.F., Balieiro, J.C.C., Pfrimer, K., Brunetto M.A., Pontieri, C.F.F. (2017). Effect of dietary protein intake on the body composition and metabolic parameters of neutered dogs. Journal of Nutritional Science. 18(6): e40. doi: 10.1017/jns.2017.41.

  19. Kocak, H., Oner-Iyidogan, Y., Gurdol, F., Oner P., Esin, D. (2011). Serum asymmetric dimethylarginine and nitric oxide levels in obese postmenopausal women. Journal of Clincal Laboratory Analysis. 25(3): 174-178. 

  20. Korkmaz, H., Asil, M., Temel, T., Ozturk B., Kebapcilar, L. (2021). Evaluation of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and their relations with disease type and activity in inflammatory bowel diseases. Turkish Journal of Medical Sciences. 51(5): 2403-2412. 

  21. Li, G., Kawasumi, K., Okada, Y., Ishikawa, S., Yamamoto, I., Arai T., Mori, N. (2014). Comparison of plasma lipoprotein profiles and malondialdehyde between hyperlipidemia dogs with/without treatment. BMC Veterinary Research. 10(1): 67. https://doi.org/10.1186/1746-6148-10-67.

  22. Li, T., Feng, R., Zhao, C., Wang, Y., Wang, J., Liu, S., Cao, J., Wang, H., Wang, T., Guo Y., Lu, Z. (2017). Dimethylarginine  dimethylaminohydrolase 1 protects against high-fat diet- induced hepatic steatosis and insulin resistance in mice. Antioxidants and Redox Signaling. 26(11): 598-609. 

  23. Liu, Y., Liu, J., Tetzlaffi, W., Paty D.W., Cynader, M.S. (2006). Biliverdin reductase, a major physiologic cytoprotectant, suppresses experimental autoimmune encephalomyelitis.  Free Radical Biology and Medicine. 40(6): 960-967. 

  24. Mah, E., Noh, S.K., Ballard, K.D., Matos, M.E., Volek J.S., Bruno, R.S. (2011). Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine: Arginine. The Journal of Nutrition. 141(11): 1961-1968. 

  25. Manna, P. and Jain, S.K. (2015). Obesity, oxidative stress, adipose tissue dysfunction and the associated health risks: Causes and therapeutic strategies. Metabolic Syndrome and Related Disorders. 13(10): 423-444. 

  26. Marliss, E.B., Chevalier, S., Gougeon, R., Morais, J.A., Lamarche, M., Adegoke O.A., Wu, G. (2006). Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover. Diabetologia.  49(2): 351-359. 

  27. Nabity, M.B., Lees, G.E., Boggess, M.M., Yerramilli, M., Obare, E., Yerramilli, M., Rakitin, A., Aguiar, J., Relford, R. (2015). Symmetric dimethylarginine assay validation, stability and evaluation as a marker for the early detection of chronic kidney disease in dogs. Journal of Veterinary Internal Medicine. 29(4): 1036-1044. 

  28. Piantedosi, D., Di Loria, A., Guccione, J., De Rosa A., Fabbri, S. (2016). Serum biochemistry profile, inflammatory cytokines,  adipokines and cardiovascular findings in obese dogs. The Veterinary Journal. 216: 72-78. 

  29. Radakovich, L.B., Truelove, M.P., Pannone, S.C., Olver C.S., Santangelo, K.S. (2017). Clinically healthy overweight and obese dogs differ from lean controls in select CBC and serum biochemistry values. Veterinary Clinical Pathology. 46(2): 221-226. 

  30. Rafaj, R.B., Kuleš, J., Turkoviæ V., Rapselj, B. (2016). Prospective hematological and biochemical evaluation of spontaneously  overweight and obese dogs. Veterinarski Arhiv. 86(3): 383-394.

  31. Sabitha, K., Venugopal, B., Rafi M.D., Ramana, K.V. (2014). Role of antioxidant enzymes in glucose and lipid metabolism in association with obesity and type 2 diabetes. American Journal of the Medical Sciences. 1: 21-24. 

  32. Surmeli, E. (2013). Measurement of asymmetrical dimethylarginine, nitric oxide and total antioxidant capacity levels in rats with experimental diabetes (Deneysel diyabet oluºturulan ratlarda; asimetrik dimetilarginin, nitrik oksit ve total antioksidan kapasite düzeylerinin ölçülmesi). Master’s Thesis, Adnan Menderes University, Institute of Health Sciences, Aydin, Turkiye. 

  33. Tabakoglu, E. and Durgut, R. (2013). Oxidative stress in veterinary medicine and the effects of oxidative stress in some important diseases (Veteriner hekimlikte oksidatif stres ve bazý önemli hastalýklarda oksidatif stresin etkileri). Avkae Journal. 3(1): 69-75. 

  34. Tomaro, M.L. and Batlle, A.M. (2002). Bilirubin: Its role in cytoprotection  against oxidative stress. International Journal of Biochemistry  and Cell Biology. 34: 216-220. 

  35. Torkanlou, K., Bibak, B., Abbaspour, A., Abdi, H., Moghaddam, M.S., Tayefi, M., Mohammadzadeh, E., Bana, H.S., Aghasizade, M., Ferns, G.A., Avan A., Mobarhan, M.G. (2016). Reduced serum levels of zinc and superoxide dismutase in obese individuals. Annals of Nutrition and Metabolism. 69 (3-4): 232-236. 

  36. Tribuddharatana, T., Kongpiromchean, Y., Sribhen K., Sribhen, C. (2011). Biochemical alterations and their relationships with the metabolic syndrome components in canine obesity. Kasetsart Journal Natural Science. 45: 622-628. 

  37. Tvarijonaviciute, A., Ceron, J.J., Holden, S.L., Cuthbertson, D.J., Biourge, V., Morris P.J., German, A.J. (2012). Obesity- related metabolic dysfunction in dogs: A comparison with human metabolic syndrome. BMC Veterinary Research. 8(1): 147. doi: 10.1186/1746-6148-8-147.

  38. Webb, C. B. and Falkowski, L. (2009). Oxidative stress and innate immunity in feline patients with diabetes mellitus: The role of nutrition. Journal of feline medicine and surgery. 11(4):  271-276. 

  39. Yamka, R.M., Friesen K.G., Frantz, N.Z. (2006). Identification of canine markers related to obesity and the effects of weight loss on the markers of interest. International Journal of Applied Research in Veterinary Medicine. 4(4): 282-292.

  40. Yvan-Charvet, L., Welch, C., Pagler, T.A., Ranalletta, M., Lamkanfi, M., Han, S., Ishibashi, M., Li, R., Wang N., Tall, A.R. (2008). Increased inflammatory gene expression in ABC transporter deficient macrophages: Free cholesterol accumulation, increased signaling via Toll-like receptors and neutrophil infiltration of atherosclerotic lesions. Circulation. 118(18): 1837-1847. 

  41. Zhong, P., Sun, D.M., Wu, D.H., Li, T.M., Liu X.Y., Liu, H.Y. (2017). Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: A community- based study. Brazilian Journal of Medical Biology and Research. 2650(2): e5252. doi: 10.1590/1414-431X20165252.

  42. Zoran, D.L. (2010). Obesity in dogs and cats: A metabolic and endocrine disorder. The Veterinary clinics of North America.  Small Animal Practice. 40(2): 221-239. 
Reviewed By

Download Article
In this Article
    Contact us
    Follow us

    Editorial Board

    View all (0)