Effect of Gum Arabic on Oxidative Stress and Inflammation in Adenine–Induced Chronic Renal Failure in Rats

Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Muscat, Sultanate of Oman.
PLoS ONE (Impact Factor: 3.23). 02/2013; 8(2):e55242. DOI: 10.1371/journal.pone.0055242
Source: PubMed


Inflammation and oxidative stress are known to be involved in the pathogenesis of chronic kidney disease in humans, and in chronic renal failure (CRF) in rats. The aim of this work was to study the role of inflammation and oxidative stress in adenine-induced CRF and the effect thereon of the purported nephroprotective agent gum arabic (GA). Rats were divided into four groups and treated for 4 weeks as follows: control, adenine in feed (0.75%, w/w), GA in drinking water (15%, w/v) and adenine+GA, as before. Urine, blood and kidneys were collected from the rats at the end of the treatment for analysis of conventional renal function tests (plasma creatinine and urea concentration). In addition, the concentrations of the pro-inflammatory cytokine TNF-α and the oxidative stress markers glutathione and superoxide dismutase, renal apoptosis, superoxide formation and DNA double strand break frequency, detected by immunohistochemistry for γ-H2AX, were measured. Adenine significantly increased the concentrations of urea and creatinine in plasma, significantly decreased the creatinine clearance and induced significant increases in the concentration of the measured inflammatory mediators. Further, it caused oxidative stress and DNA damage. Treatment with GA significantly ameliorated these actions. The mechanism of the reported salutary effect of GA in adenine-induced CRF is associated with mitigation of the adenine-induced inflammation and generation of free radicals.

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    • "We have previously shown, in rats, that GA possesses both anti-oxidant and anti-inflammatory properties (Ali et al., 2010), and this might be the basis of its beneficial effect in the adenine-induced CRF. The possible mechanism by which GA ameliorates adenine-induced CRF has been discussed before (Ali et al., 2013). Here, we have confirmed the salutary action of GA in adenine CRF in both mice and rats. "
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    ABSTRACT: Introduction: This study aimed at comparing the effects of feeding mice and rats with adenine to induce a state of chronic renal failure (CRF), and to assess the effect of treatment with gum acacia (GA) thereon. Methods: We compared the outcome, in mice, of feeding adenine at three different doses (0.75%, 0.3%, and 0.2%, w/w). Biochemical and histopathological studies were conducted in plasma, urine and renal homogenates from both species. Results: When mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1-2 days. The dosage in mice was reduced to 0.3%, w/w, for 4 weeks, but again all treated mice died within 3-4 days. A further reduction in the dosage in mice to 0.2%, w/w, for 4 weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4 weeks. Plasma creatinine, urea and urinary protein were significantly increased (P<0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P<0.05), reversed by GA. Adenine significantly (P<0.001) reduced superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P<0.05) ameliorated by GA. Discussion: Our data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4 weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4 weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.
    Journal of pharmacological and toxicological methods 05/2013; 68(3). DOI:10.1016/j.vascn.2013.05.001 · 2.39 Impact Factor
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    • "The remaining glomeruli did not show extensive signs of sclerosis or mesangiolysis . The fibrosis and inflammation indices on the other hand were similar to our last study (Ali et al., 2013a). "

    The FASEB Journal 01/2013; 27:889.1. · 5.04 Impact Factor
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    ABSTRACT: Gum arabic (GA), a water-soluble dietary fiber rich in Ca(2+), Mg(2+) and K(+), is used in Middle Eastern countries for the treatment of patients with chronic kidney disease. Recent animal experiments shed some light into mechanisms involved in the therapeutic action of GA. According to experiments in healthy mice, GA treatment increases creatinine clearance, enhances renal excretion of ADH, Mg(2+) and Ca(2+), decreases plasma phosphate concentration as well as urinary excretion of phosphate and Na(+). In diabetic mice GA treatment increases urinary Ca(2+) excretion, and decreases plasma phosphate concentration, plasma urea concentration, urinary flow rate, natriuresis, phosphaturia, glucosuria, proteinuria as well as blood pressure. Extrarenal effects of GA treatment in mice include decreased expression of intestinal Na(+) coupled glucose carrier SGLT1 with subsequent delay of electrogenic intestinal glucose transport, glucose-induced hyperglycemia, hyperinsulinemia and body weight gain. GA treatment decreases colonic transcription of the angiogenetic factors angiogenin 1, angiogenin 3 and angiogenin 4, of CD38 antigen, aquaporin4, interleukin18, vav-3-oncogene, y(+)-amino acid-transporter, sulfatase1, ubiquitinD and chemokine ligand5. Moreover, GA treatment decreases angiogenin and ß-catenin protein expression. Accordingly, GA treatment counteracts the development of tumors following chemical cancerogenesis. In mouse dendritic cells, antigen-presenting cells linking innate and adaptive immunity, GA treatment modifies maturation and cytokine release. GA treatment further favourably influences the course of murine malaria. The effects of GA treatment on plasma phosphate concentration, blood pressure and proteinuria may prove beneficial in chronic renal failure and diabetic nephropathy. The effect of GA on intestinal glucose transport may be useful in the prophylaxis and treatment of obesity and diabetes, the effect of GA on angiogenin and ß-catenin expression could be exploited for the prophylaxis against colon carcinoma, the effects of GA on angiogenin expression and dendritic cells may be useful in the treatment of inflammatory disease and malaria. © 2013 S. Karger AG, Basel.
    Kidney and Blood Pressure Research 08/2013; 37(4-5):269-279. DOI:10.1159/000350152 · 2.12 Impact Factor
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