The aim of this study was to investigate some biochemical indices of inflammation and oxidative and nitrosative stresses in the gastrointestinal tract of mice with experimental chronic kidney disease (CKD) and treated with gum arabic (GA). Male CD1 mice (n = 28) were randomly distributed into four groups and treated for four consecutive weeks: group 1: Control: received the same diet without treatment until the end of the study; group 2: Adenine: switched to a powder diet containing adenine (0.2% w/w in feed); group 3: Gum acacia (GA): given normal feed and GA in drinking water at a concentration of 15% w/v; and group 4: Adenine + GA: given adenine in the feed as in the second group plus GA in the drinking water at concentration of 15% w/v. CKD was induced to mice by adenine feeding and concomitantly treated with the prebiotic dietary fiber gum acacia, GA (15% in drinking water). Duodenal mucosa from CKD mice had significantly higher concentrations of TNF-alfa, IL- 6, and TGF-beta-1 and lipid peroxidation. Moreover, low concentrations of IL-10, some antioxidants (catalase, glutathione reductase, total antioxidant capacity, and superoxide dismutase), and nuclear factor erythroid 2–related factor 2 were found in the duodenum. The levels of nitrosative stress (nitrite, nitrate, and total nitrate) were significantly increased by CKD, as well as the concentrations of ammonia and urea creatinine in the cecal content. Concomitant GA treatment significantly mitigated these harmful effects. Taken together, GA reduces inflammation and duodenal oxidative and nitrosative stress in the gastrointestinal tract of mice with CKD.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Ahmed AA, Fedail JS, Musa HH, Kamboh AA, Sifaldin AZ, Musa TH (2015) Gum arabic extracts protect against hepatic oxidative stress in alloxan induced diabetes in rats. Pathophysiology 22(4):189–194
Al Za’abi M, Al Busaidi M, Yasin J, Schupp N, Nemmar A, Ali BH (2015) Development of a new model for the induction of chronic kidney disease via intraperitoneal adenine administration, and the effect of treatment with gum acacia thereon. Am J Transl Res 7:28–38
Al Za’abi M, Shalaby A, Manoj P, Ali BH (2017) The in vivo effects of adenine -induced chronic kidney disease on some renal and hepatic function and CYP450 metabolizing enzymes. Physiol Res 66:263–271
Al Za’abi M, Al Salam S, Al Suleimani Y, Manoj P, Nemmar A, Ali BH (2018) Gum acacia improves renal function and ameliorates systemic inflammation, oxidative and nitrosative stress in streptozotocin-induced diabetes in rats with adenine-induced chronic kidney disease. Cell Physiol Biochem 45:2293–2304
Ali BH, Al-Husseni I, Beegam S, Al-Shukaili A, Nemmar A, Schierling S, Queisser N, Schupp N (2013) Effect of gum arabic on oxidative stress and inflammation in adenine - induced chronic renal failure in rats. PLoS One 8(2):e55242
Ali BH, Al Balushi K, Al-Husseini I, Mandel P, Nemmar A, Schupp N, Ribeiro DA (2015) Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats. Eur J Clin Investig 45(12):1221–1227
Ali BH, Al Salam S, Al Suleimani Y, Al Za’abi M, Abdelrahman AM, Ashique M, Manoj P, Adham SA, Hartmann C, Schupp N, Nemmar A (2019) Effects of the SGLT-2 inhibitor canagliflozin on adenine-induced chronic kidney disease in rats. Cell Physiol Biochem 52:27–39
Bao YW, Yuan Y, Chen JH, Lin WQ (2018) Kidney disease models: tools to identify mechanisms and potential therapeutic targets. Zool Res 39:72–86
Braga VNL, Juanes CC, Peres Júnior HS, Sousa JR, Cavalcanti BC, Jamacaru FVF, Lemos TLG, Dornelas CA (2019) Gum arabic and red propolis protecteting colorectal preneoplastic lesions in a rat model of azoxymethane. Acta Cir Bras 34(2):e201900207
Claramunt D, Gil-Peña H, Fuente R, García-López E, Loredo V, Hernández-Frías O, Ordoñez FA, Rodríguez-Suárez J, Santos F (2015) Chronic kidney disease induced by adenine: a suitable model of growth retardation in uremia. Am J Physiol Renal Physiol 309:F57–F62
Cosola C, Rocchetti MT, Cupisti A, Gesualdo L (2018) Microbiota metabolites: pivotal players of cardiovascular damage in chronic kidney disease. Pharmacol Res 130:132–142
Dandekar A, Mendez R, Zhang K (2015) Cross talk between ER stress, oxidative stress, and inflammation in health and disease. Methods Mol Biol 1292:205–214
de Frutos S, Luengo A, García-Jérez A, Hatem-Vaquero M, Griera M, O'Valle F, Rodríguez-Puyol M, Rodríguez-Puyol D, Calleros L (2019) Chronic kidney disease induced by an adenine rich diet upregulates integrin linked kinase (ILK) and its depletion prevents the disease progression. Biochim Biophys Acta Mol Basis Dis
Deloose E, Verbeure W, Depoortere I, Tack J (2019) Motilin: from gastric motility stimulation to hunger signalling. Nat Rev Endocrinol 15:238–250
Diwan V, Brown L, Gobe GC (2018) Adenine - induced chronic kidney disease in rats. Nephrology (Carlton) 23:5–11
Dos Santos IF, Sheriff S, Amlal S, Ahmed RP, Thakar CV, Amlal H (2019) Adenine acts in the kidney as a signaling factor and causes salt- and water-losing nephropathy: early mechanism of adenine-induced renal injury. Am J Physiol Renal Physiol 31:F743–F757
Gluhovschi G, Velciov S, Petrica L, Gluhovschi C (2014) Aspects of renal - pulmonary pathogenic relationships in chronic kidney disease and chronic pulmonary diseases — a less-known connection. Rom J Intern Med 52:68–77
Gluhovschi G, Petrică L, Sporea I, Timar R, Curescu M, Velciov S, Gluhovschi C (2015) Chronic kidney disease - chronic liver disease. An immunologic cross-talk. Rom J Intern Med 53:3–12
Hammad FT, Salam SA, Nemmar A, Ali M, Lubbad L (2019) The effect of Arabic gum on renal function in reversible unilateral ureteric obstruction. Biomolecules 11:9(1)
Hung TV, Suzuki T (2018) Dietary fermentable fibers attenuate chronic kidney disease in mice by protecting the intestinal barrier. J Nutr 148:552–561
Ishimoto Y, Tanaka T, Yoshida Y, Inagi R (2018) Physiological and pathophysiological role of reactive oxygen species and reactive nitrogen species in the kidney. Clin Exp Pharmacol Physiol 45:1097–1105
Kaddam L, Fadl-Elmula I, Eisawi OA, Abdelrazig HA, Salih MA, Lang F, Saeed AM (2017) Gum arabic as novel anti-oxidant agent in sickle cell anemia, phase II trial. BMC Hematol 17:4
Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL (2017) Oxidative stress in atherosclerosis. Curr Atheroscler Rep 19(11):42
Kitazawa T, Kaiya H (2019) Regulation of gastrointestinal motility by motilin and ghrelin in vertebrates. Front Endocrinol (Lausanne) 10:278
Kujal P, Vernerová Z (2008) 5/6 nephrectomy as an experimental model of chronic renal failure and adaptation to reduced nephron number. Cesk Fysiol 57:104–109
Kume T (2017) Therapeutic potential of the activators of the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway in brain disorders. Biol Pharm Bull 40(5):553–556
Lim PS, Chang YK, Wu TK (2019) Serum lipopolysaccharide-binding protein is associated with chronic inflammation and metabolic syndrome in hemodialysis patients. Blood Purif 47:28–36
Lv W, Booz GW, Fan F, Wang Y, Roman RJ (2018) Oxidative stress and renal fibrosis: recent insights for the development of novel therapeutic strategies. Front Physiol 9:105
Ma Q (2013) Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426
Mazumder MK, Paul R, Bhattacharya P, Borah A (2019) Neurological sequel of chronic kidney disease: from diminished acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain. Sci Rep 9(1):3097
Meijers B, Farré R, Dejongh S, Vicario M, Evenepoel P (2018) Intestinal barrier function in chronic kidney disease. Toxins (Basel) 10(7):298
Nemmar A, Karaca T, Beegam S, Yuvaraju P, Yasin J, Ali BH (2017) Lung oxidative stress, DNA damage, apoptosis, and fibrosis in adenine-induced chronic kidney disease in mice. Front Physiol 8:896
Nemmar A, Al-Salam S, Beegam S, Yuvaraju P, Ali BH (2019) Gum arabic ameliorates impaired coagulation and cardiotoxicity induced by water-pipe smoke exposure in mice. Front Physiol 10:53
Ojo A (2014) Addressing the global burden of chronic kidney disease through clinical and translational research. Trans Am Clin Climatol Assoc 125:229–243
Onal EM, Afsar B, Covic A, Vaziri ND, Kanbay M (2019) Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease. Hypertens Res 42:123–140
Ortiz A, Sanchez-Niño MD, Izquierdo MC, Martin-Cleary C, Garcia-Bermejo L, Moreno JA, Ruiz-Ortega M, Draibe J, Cruzado JM, Garcia-Gonzalez MA, Lopez-Novoa JM, Soler MJ, Sanz AB (2015) Red de Investigacion Renal (REDINREN) and Consorcio Madrileño para investigación del fracaso renal agudo (CIFRA). Translational value of animal models of kidney failure. Eur J Pharmacol 759:205–220
Santana AC, Degaspari S, Catanozi S, Dellê H, de Sá LL, Silva C, Blanco P, Solez K, Scavone C, Noronha IL (2013) Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice. Nephrol Dial Transplant 28(5):1140–1149
Shuvy M, Nyska A, Beeri R, Abedat S, Gal-Moscovici A, Rajamannan NM, Lotan C (2011) Histopathology and apoptosis in an animal model of reversible renal injury. Exp Toxicol Pathol 63:303–306
Vaziri ND, Yuan J, Nazertehrani S, Ni Z, Liu S (2013) Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction. Am J Nephrol 38:99–103
Wang X, Luo S, Liu Y (1996) Effects of changes of plasma motilin level on the motility of gallbladder in patients with chronic renal failure. Zhonghua Nei Ke Za Zhi 35:86–88
Wu GJ, Cai XD, Xing J, Zhong GH, Chen JDZ (2017) Circulating motilin, ghrelin, and GLP-1 and their correlations with gastric slow waves in patients with chronic kidney disease. Am J Physiol Regul Integr Comp Physiol 313:R149–R157
Yang T, Richards EM, Pepine CJ, Raizada MK (2018) The gut microbiota and the brain-gut- kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol 14:442–456
Yokozawa T, Zheng PD, Oura H, Koizumi F (1986) Animal model of adenine- induced chronic renal failure in rats. Nephron 44:230–234
Zhu Z, Sun L, Hao R, Jiang H, Qian F, Ye RD (2017) Nedd8 modification of Cullin-5 regulates lipopolysaccharide-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 313:L104–L114
We thank the staff of SQU Animal Facility for looking after the animals.
This work was supported financially by an internal grant (SQU). DAR is a researcher on Productivity at CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico), level 1C.
Ethical approval for conducting the work was obtained from Sultan Qaboos University (SQU) Animal Ethics Committee, on 12.12.2017, code # (SQU/AEC/2017-15). All procedures involving animals and their care were carried out in accordance with international laws and policies (EEC Council directives 2010/63/EU, September 22, 2010 and NIH Guide for the Care and Use of Laboratory Animals).
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by Animal Ethics Committee from Sultan Qaboos University (SQU) Animal Ethics Committee, on 12.12.2017, code # (SQU/AEC/2017-15).
For this type of study, formal consent is not required.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Ali, B.H., Al Za’abi, M., Al Suleimani, Y. et al. Gum arabic reduces inflammation, oxidative, and nitrosative stress in the gastrointestinal tract of mice with chronic kidney disease. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1427–1436 (2020). https://doi.org/10.1007/s00210-020-01844-y