The effect of glibenclamide on performance, carcass characteristics, blood parameters, immunity, intestinal microbial flora, intestinal morphology and breast muscle fatty acid profile in broilers

Document Type : Research Paper

Authors

Department of Animal Science, Rasht Branch, Islamic Azad University, Rasht, Iran

Abstract

Glibenclamide, with IUPAC name chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl] phenethyl)-2-methoxybenzamide, is a sulfonylurea derivative with a melting point of 169-174 ◦C. This substance is in the form of a white crystalline powder, often without smell and taste, insoluble in water but soluble in methylene chloride. Glibenclamide is classified as sulfonylurea drugs which act by stimulating beta cells of the pancreas to secrete more insulin throught increased intercellular cAMP. These drugs are only effective in people who have minimal ability to secrete insulin. At the same time, these drugs have been suggested to increase the binding of insulin to receptors and increase the number of insulin receptors (Rambiritch et al., 2007). Recent studies have reported that glibenclamide also plays a role in the hypoglycemic effects in the regulation of inflammation. No data are available regarding the effect of glibenclamide in broilers and whether glibenclamide can have an effect on performance, carcass characteristics, blood parameters, immunity, intestinal microbial flora, intestinal morphology, and fatty acid profile and not clear whether it is benefit in chicken or not and it needs further investigation. This research was conducted in 2022 at a broiler farm located in Rasht. The trial utilized 120 one-day-old broiler chickens of the commercial strain Ross 308 with an average weight of 43±1g. The experiment was conducted as a completely randomized design with 3 treatments and 4 replications of 10 chickens per pen for 42 days. Experimental treatments include three dietary concentrations of glibenclamide: 0 (Control), 75, or 100 mg/kg glibenclamide). The ration was formulated to meet the minimum nutritional requirements of the Ross 308 strain. Chickens were reared in 1×1 m cages on a bed of cellulose rolls for 42 days. The weight gain of all chickens in each pen was calculated by a digital scale with an accuracy of ±10 g during periods of 1 to 10, 11 to 21, and 22 to 42 d. At the end of each period, the amount of remaining feed (beginning 1 to 10, growth 11 to 21 and ending 22 to 42) at the beginning of each period, the amount of feed consumed was calculated by weighing in each feeder and deducting from the amount of feed given. Also, feed conversion was calculated by dividing the amount of feed consumption by the weight gain for days 1 to 10, 11 to 21, and 22 to 42 and the entire period. Economic efficiency, carcass characteristics, digestive organs, blood parameters, immune responses, intestinal microbial flora, intestinal morphology, and breast fatty acid profile were measured. All data collected during the experiment and laboratory traits were analyzed by analyses of variance using statistical software. Means were compared with Duncan's multiple range test at 5% statistical levels. The results indicate that during all of the growing periods, the use of glibenclamide did not affect the performance of broiler chickens (P≥0.05). Also, weight at 42 d of age, feed cost per kg live weight (Rial/kg), and European index were not different among dietary concentrations of glibenclamide (P≥0.05). Use of two different levels of glibenclamide did not have a difference on live weight, featherless weight, thigh percentage, breast percentage and abdominal fat (P≥0.05), but 75 mg/kg was reported to reduce fat in the ventricular area. Glibenclamide did not affect blood glucose concentrations (P>0.05). Feeding 0 or 75 mg/kg of glibenclamide as a sulfonylurea derivative reduced cholesterol, triglycerides, HDL, VLDL and LDL concentrations (P<0.05). The LDL to HDL ratio was highest for 75 compared with 0 and 100 mg/kg glibenclamide (P<0.05). In contrast, concentrations of total protein, albumin and globulin were greatest for 0 mg/kg, intermediate for 75 mg/kg and highest for 100 mg/kg (P<0.05). No differences were observed among treatments on humoral immune system function in response to SRBC antigen injection, except for 35 d which was highest for 100 mg/kg glibenclamide, and antibody titer against Newcastle virus and influenza (Table 7). In response to SRBC antigen injection, Newcastle and influenza titers increased at the end of the course. Feeding glibenclamide did not increase the relative weight of the bursa of Fabricius or the weight of the spleen (P≥0.05). Feeding 0 or 75 mg/kg glibenclamide supported lower numbers of Escherichia coli bacteria compared to other treatments (P<0.05); however, no differences were observed in the number of Lactobacillus acidophilus. The highest villi length was observed with the consumption of 75 mg/kg glibenclamide. The depth of the crypt increased in the same dose of glibenclamide compared to the control group, but the ratio of villi length to the depth of the crypt decreased. The results indicate that lower percentages of myristic and palmitic acid were observed when 75 mg/kg of glibenclamide was fed compared with 100 mg/kg; however, palmitoleic, steric, oleic, linoleic, and linolenic acid percentages were lowest and the ratio of saturated to unsaturated fatty acids was highest when 100 kg/kg of glibenclamide was fed. In general, the results of this trial indicate that glibenclamide does not improved feed consumption, weight gain, conversion rate, total cost per kilogram of live chicken and production index in the rearing period. However, feeding low concentrations could reduce abdominal fat. Feeding low concentrations of glibenclamide led to a positive effect on blood factors, including triglycerides, cholesterol, VLDL, LDL, total protein. Populations of Escherichia coli were reduced in the intestine which appeared to improve villi length and crypt depth as well as the ratio of villi length to crypt depth compared to the control group. In comparison of saturated and unsaturated fatty acids, its low dose was able to reduce the ratio of saturated to unsaturated fatty acids. Therefore, according to the positive effects of glibenclamide on performance, carcass characteristics, blood parameters, immunity, intestinal flora, intestinal morphology and fatty acid profile, this food additive can be used as an alternative to commercial antibiotics and a cheap growth promoter.

Keywords

Main Subjects


Abbas A, Zubair M, Rasool N and Rizwan K, 2015. Antimicrobial potential of Glycyrrhiza glabra. Journal of Drug Design and Medicinal Chemistry 1(2): 17-20.
Adeshara K and Tupe R, 2016. Antiglycation and cell protective actions of metformin and glipizide in erythrocytes and monocytes. Molecular Biology Reports 43: 195-205.‏
Al-Sultany D, Hasan AB, Ali EA, and Sahib TR, 2013. Effect of Glibenclamide drug on some productive characteristics of meat Chicken. Proceedings of 2nd International Conference on Agriculture and Natural Resources. Razi University, Kermanshah, Iran. pp 21-27.
Al-Taraji HJ, 2012. Influence of drinking water supplementation with licorice extract on certain blood traits of broiler chickens during heat stress. Pharmacognosy Communications 2(4): 29-33.‏
Al-Qarawi AA, Abdel-Rahman HA, Ali BH and El Mougy SA, 2002. Liquorice (Glycyrrhiza glabra) and the adrenal-kidney-pituitary axis in rats. Food and chemical toxicology 40(10): 1525-1527.‏
Al-Razzuqi R, Al-Jawad FH, Al-Hussaini JA and Al-Jeboori A, 2012. Hepatoprotective effect of Glycyrrhiza glabra in carbon tetrachloride-induced model of acute liver injury. Journal of Physiology and Pharmacology Advance 2(7): 259-263.‏
Al-Snafi AE, 2018. Glycyrrhiza glabra: A phytochemical and pharmacological review. IOSR Journal of Pharmacy 8(6): 1-17.‏
Ansel Richard S, 2005. Clinical anatomy. Translation: Hassanzadeh Gholamrazaf, Fath Elahi Alireza, volume 1-Tanhaf, Nesl Farda Publications, 1st edition, 6th edition, 1381.
Armanini D, De Palo CB, Mattarello MJ, Spinella P, Zaccaria M, Ermolao A, Palermo M, Fiore C, Sartorato P, Francini-Pesenti F and Karbowiak I, 2003. Effect of licorice on the reduction of body fat mass in healthy subjects. Journal of Endocrinological Investigation 26: 646-650.‏
Armanini D, Fiore C, Mattarello MJ, Bielenberg J and Palermo M, 2002. History of the endocrine effects of licorice. Experimental and Clinical Endocrinology and Diabetes 110(06) 257-261.‏
Arvelo F, Sojo F and Cotte C, 2015. Biology of colorectal cancer. Ecancermedica Science, 9.‏
Awadein NB, Eid YZ and Abd El-Ghany FA, 2010. Effect of dietary supplementation with phytoestrogens sources before sexual maturity on productive performance of mandarah hens. Poultry Science 30(3): 829-846.‏
Aziz MA, Khan AH, Adnan M and Ullah H, 2018. Traditional uses of medicinal plants used by Indigenous communities for veterinary practices at Bajaur Agency, Pakistan. Journal of Ethnobiology and Ethnomedicine 14(1): 1-18.‏
Baker ME, 1994. Licorice and enzymes other than 11β-hydroxysteroid dehydrogenase: an evolutionary perspective. Steroids 59(2): 136-141.‏
Benko S, Philpott DJ and Girardin SE, 2008. The microbial and danger signals that activate Nod-like receptors. Cytokine 43(3): 368-373.
Codreanu I, Aschembrener C, Constantinescu I and Codreanu, M, 2009. Studies concerning the effect of glibenclamide, streptozotocine, and insulin upon pancreatic juice flow and pancreatic amylase and lipase activity, in hens. Lucrări Științifice-Medicină Veterinară, Universitatea de Științe Agricole și Medicină Veterinară" Ion Ionescu de la Brad" Iași, 52(11): 62-69.
Dibaji SM, Seidavi A, Asadpour L and Moreira da Silva F, 2014. Effect of a symbiotic on the intestinal microflora of chickens. Journal of Applied Poultry Research, 23(1): 1-6.
Donahue SR, Turner KC and Patel S, 2002. Pharmacokinetics and pharmacodynamics of glyburide/metformin tablets (Glucovance™) versus equivalent doses of glyburide and metformin in patients with type 2 diabetes. Clinical Pharmacokinetics 41: 1301-1309.
Felipa A, Xochitl T, Enrique S, Rocıo M, Alfredo S, Monica O and Miguel H, 2011. Glibenclamide increases post-fatigue tension in slow skeletal muscle fibers of the chicken". Journal of Comparative Physiology B. 181: 403-412.
Erejuwa OO, Sulaiman SA, Wahab MSA, Salam SKN, Salleh MSM and Gurtu S, 2011. Comparison of antioxidant effects of honey, glibenclamide, metformin, and their combinations in the kidneys of streptozotocin-induced diabetic rats. International Journal of Molecular Sciences 12(1): 829-843.
Folch J, Lees M and Stanley GS, 1957. A simple method for the isolation and purification of total lipides from animal tissues. Journal of Biological Chemistry 226(1): 497-509.
Ghosian MMH, Khalli NM, Ghasemi DS, and Shoja SF, 2015. Therapeutic effect of a combination of caffeine and glibenclamide on serum glucose and lipids in type 2 diabetic rats.‏ Shahed University,10.
Gilani SRM and Feizabad AK, 2019. The effects of aerobic exercise training on mental health and self-esteem of type 2 diabetes mellitus patients. Health Psychology Research 7(1).‏
Golrokh AJ, Bouyeh M, Seidavi A, van den Hoven R, Laudadio V and Tufarelli V, 2016. Effect of different dietary levels of atorvastatin and L-carnitine on performance, carcass characteristics and plasma constitutes of broiler chickens. The Journal of Poultry Science 53(3): 201-207.
Gore AB and Qureshi MA, 1997. Enhancement of humoral and cellular immunity by vitamin E after embryonic exposure. Poultry Science 76(7): 984-991.
Guyton AC, and Hall JE, 2011. Textbook of medical physiology. 12th ed. Philadelphia. USA: Saunders.
Haj HV, Rabani M, Asghari GR and Karami SZ, 2004. Effects of Otostegia persica (Burm.) Boiss on morphine withdrawal syndrome in mice.‏ Iranian Journal of Pharmaceutical Research 3: 171- 175.
Hanrahan JR, Chebib M and Johnston GA, 2011. Flavonoid modulation of GABAA receptors. British Journal of Pharmacology 163(2): 234-245.‏
Harper Harold A, 2004. Harper Biochemistry. Translation: Karimzadeh Hamidreza, Behabhari Alireza, Noormohamedian Maryam. Under the supervision of Malik Niya Nasser, Shahbazi Parviz. Shahr Ab Publications 177-343.
Henquin JC, 2021. Glucose-induced insulin secretion in isolated human islets: Does it truly reflect β-cell function in vivo?. Molecular Metabolism 48: 101212.
Hosseintabar B, Dadashbeiki M, Bouyeh M and Seidavi A, 2014. Is the amount of l-carnitine and methionine-lysine affect on the microbial flora of broiler cecum. Journal of Pure and Applied Microbiology 8(1): 353-360.
Huang YS, Huang WC, Li CW and Chuang LT, 2011. Eicosadienoic acid differentially modulates production of pro-inflammatory modulators in murine macrophages. Molecular and Cellular Biochemistry 358(1-2): 85-94.
Ishibashi Y, Matsui T, Takeuchi M and Yamagishi S, 2012. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression. Hormone and Metabolic Research 44(12): 891-895.‏
Jang IS, Ko YH, Kang SY and Lee CY, 2007. Effect of a commercial essential oil on growth performance, digestive enzyme activity and intestinal microflora population in broiler chickens. Animal Feed Science and Technology 134(3-4): 304-315.
Jun Quira L, Carlos Carneiro JA and Kelly R, 2013. Basic histology. Translated by Montazeri Mahdi, because Bahadri Muslim's opinion. Arjmand Publications, 10th edition, Tehran, 1389, pages 21-6.
Kagami K, Morita H, Onda K, Hirano T and Oka K, 2008. Protective effect of caffeine on streptozotocin-induced beta-cell damage in rats. Journal of Parmacy and Pharmacology, 60(9): 1161-1165.
Kalantari-Hesari A, Morovvati H, Babaei M, Nourian A, Esfandiari K, Elmi T and Soltani S, 2022. Modified methods to simplification histochemical, immunohistochemical, and hematoxylin-eosin staining. Iranian Veterinary Journal 18(3): 63-73.‏
Koh GC, Weehuizen TA, Breitbach K, Krause K, de Jong HK, Kager LM, Hoogendijk AJ, Bast A, Peacock SJ, Poll TVD, Steinmetz L and Wiersinga WJ, 2013. Glyburide reduces bacterial dissemination in a mouse model of melioidosis. PLoS Neglected Tropical Diseases 7(10): e2500.‏
Larypoor M, Akhavan Sepahy E and Tabatabaee Alavi A, 2020. Investigating the effect of synergistic glycyrrhiza glabra and astraglus gossypinus on improvement of gastrointestinal wound in rats. Iranian Journal of Medical Microbiology 14(4): 314-341.
Lerner KG, Glick B and McDuffie FC, 1971. Role of the bursa of Fabricius in IgG and IgM production in the chicken: evidence for the role of a non-bursal site in the development of humoral immunity. The Journal of Immunology 107(2): 493-503.
Li J, Wu Y, Zhang S, Zhang J, Ji F, Bo W and Li Z, 2015. Baicalein protect pancreatic injury in rats with severe acute pancreatitis by inhibiting pro-inflammatory cytokines expression. Biochemical and Biophysical Research Communications 466(4): 664-669.
Liao MZ, 2018. Understanding Pregnancy-induced Changes in the Disposition of Norbuprenorphine, Metformin and Glyburide in Mice and Humans for Optimizing Drug Therapy during Pregnancy (Doctoral dissertation).‏ University of Washington, USA. 191pp.
Mirershadi F, Ogagzadeh H, Faghihi M and Alizadeh L, 2015. Role of nitric-oxide in cardiac effects of glibenclamide in rat. Journal of Inflammatory Diseases 19(1): 17-23.‏
Mohseni S, Tabatabaei MO, Bandarian F and Larijani B, 2022. Pharmacogenomics of glibenclamide in patients with type 2 diabetes mellitus: A systematic review.‏ Koomesh -Volume 24, Issue 2 “Personalized Medicine Supplement”, 183-190.
Naddaf-Fahmideh M, Seidavi A and Bouyeh M, 2023. The effect of different levels of vitamin C on performance, carcass characteristics, digestive organs, immunity, blood parameters, liver enzymes, cecal microflora, evaluation of meat taste and fatty acid profile of breast meat of broilers. Journal of the Hellenic Veterinary Medical Society 74(4): 6525-6542.
Ocak N, Erener G, Ak F, Sungu M, Altop A and Ozmen A, 2008. Performance of broilers fed diets supplemented with dry peppermint (Mentha piperita L.) or thyme (Thymus vulgaris L.) leaves as growth promoter source. Czech Journal of Animal Science 53(4).
Phillips CJ, Hosseintabar-Ghasemabad B, Gorlov IF, Slozhenkina MI, Mosolov AA and Seidavi A, 2023. Immunomodulatory effects of natural feed additives for meat chickens. Life 13(6): 1287.‏
Pourhossein Z, Qotbi AAA, Seidavi A, Laudadio V, Centoducati G and Tufarelli V, 2015. Effect of different levels of dietary sweet orange (Citrus sinensis) peel extract on humoral immune system responses in broiler chickens. Animal Science Journal 86(1): 105-110.
Qousian Moghadam MH, Khalili Najafabadi M, Ghasemi Daulatabadi S and Shoja Shafiei F, 2014. The therapeutic effect of the combination of caffeine and glybenclamide on serum lipids and glucose in type 2 diabetic rats. Daneshvar Mezizi 22(116): 70-65.
Rambiritch V, Naidoo P and Butkow N, 2007. Dose-response relationships of sulfonylureas: will doubling the dose double the response? Southern Medical Journal 100(11): 1132-1136.
Ryan RM, Ahmed Q and Lakshminrusimha S, 2008. Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia. Clinical Reviews in Allergy and Immunology 34: 174-190.
Sahin K, Orhan C, Smith MO and Sahin N, 2013. Molecular targets of dietary phytochemicals for the alleviation of heat stress in poultry. World's Poultry Science Journal 69(1): 113-124.
Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, van Teunenbroek A, van Leeuwen WJ, Asarfi A, Rijn RRV and Drop SL, 2001. Bone mineral density assessed by phalangeal radiographic absorptiometry before and during long-term growth hormone treatment in girls with Turner's syndrome participating in a randomized dose-response study. Pediatric research 50(3): 417-422.‏
Seidavi A, Hosseintabar-Ghasemabad B, Gorlov IF, Slozhenkina MI, Mosolov AA, Oteri M, Chiofalo B and Liotta L, 2023. Feed Additives and Future Perspectives. In Sustainable Use of Feed Additives in Livestock: Novel Ways for Animal Production (pp. 929-961). Springer International Publishing.
Shahabinejad S, 2006. Determining the prevalence of fatty liver in sonography in the age group of 30-60 years in Zahedan city. Doctoral thesis in radiology, number T-205, Zahedan University of Medical Sciences.
Sigolo S, Deldar E, Seidavi A, Bouyeh M, Gallo A and Prandini A, 2019. Effects of dietary surpluses of methionine and lysine on growth performance, blood serum parameters, immune responses, and carcass traits of broilers. Journal of Applied Animal Research 47(1): 146-153.
Silvares RR, Pereira ENGDS, Flores EEI, Estato V, Reis PA, Silva IJD and Daliry A, 2016. Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high‐fat diet‐/streptozotocin‐induced diabetes. International journal of experimental pathology, 97(3): 266-277.‏
Tanaka Y, Uchino H, Shimizu T, Yoshii H, Niwa M, Ohmura C, Mitsuhashi N, Onuma T and Kawamori R, 1999. Effect of metformin on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats. European Journal of Pharmacology 376(1-2): 17-22.
Van der Zipp AJ, Frankena K, Boneschancher J and Nieuwland MGB, 1983. Gentic analysis of primary and secondary immune response in the chicken. Poultry Science 62: 565-572.
Visavadiya NP, Soni B and Dalwadi N, 2009. Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models. International Journal of Food Sciences and Nutrition 60(sup2): 135-149.‏
Wang X, Lin H and Gu Y, 2012. Multiple roles of dihomo-γ-linolenic acid against proliferation diseases. Lipids in Health and Disease 11(1): 25.
Woodhari S, 1999. Familiarity with diabetes. Translated by Khazaei Mohsen et al. Publications of Mashhad University of Medical Sciences, 1375, p. 25.
Wright DC, Hucker KA, Holloszy JO and Han DH, 2004. Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions. Diabetes 53(2): 330-335.
York JM, Castellanos KJ, Cabay RJ and Fantuzzi G, 2014. Inhibition of the nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 inflammasome reduces the severity of experimentally induced acute pancreatitis in obese mice. Translational Research 164(4): 259-269.
Zhang T, Hu X, Cai Y, Yi B and Wen Z, 2014. Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein. Molecular Biology Reports 41: 1335-1340.