Effect of gum arabic on oxidative stress and inflammation in adenine-induced chronic renal failure in rats

Badreldin H Ali, Isehaq Al-Husseni, Sumyia Beegam, Ahmed Al-Shukaili, Abderrahim Nemmar, Simone Schierling, Nina Queisser, Nicole Schupp, Badreldin H Ali, Isehaq Al-Husseni, Sumyia Beegam, Ahmed Al-Shukaili, Abderrahim Nemmar, Simone Schierling, Nina Queisser, Nicole Schupp

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Plasma creatinine (A) and creatinine…
Figure 1. Plasma creatinine (A) and creatinine clearance (B), as well as proteinuria (C) in control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days.
Each column and vertical bar represents the mean ± SEM (n = 6). ** p# p≤0.05, ### p<0.001 vs. adenine treatment.
Figure 2. Occurrence of inflammation (A) in…
Figure 2. Occurrence of inflammation (A) in kidneys of control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days.
Black arrows in the representative pictures of tissue stained with hemytoxylin point to leucocyte infiltration. Occurrence of fibrosis (B) in the kidneys of control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days. Shown are representative pictures of fibrosis in the kidney, with black arrows pointing to examples of collagen disposition, visualized by Sirius Red staining.
Figure 3. Plasma C-reactive protein concentration in…
Figure 3. Plasma C-reactive protein concentration in control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days.
Each column and vertical bar represents the mean ± SEM (n = 6). # p≤0.05 vs. adenine treatment.
Figure 4. Tumor necrosis factor-α concentration in…
Figure 4. Tumor necrosis factor-α concentration in urine (A) and plasma (B) in control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days.
Each column and vertical bar represents the mean ± SEM (n = 6). ** p# p<0.05, ## p<0.01,### p<0.001 vs. adenine treatment.
Figure 5. Interleukin 10 (IL-10) concentration in…
Figure 5. Interleukin 10 (IL-10) concentration in the plasma of control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days.
Each column and vertical bar represents the mean ± SEM (n = 6). *** p### p<0.001 vs. adenine treatment.
Figure 6. Representative pictures of superoxide formation…
Figure 6. Representative pictures of superoxide formation visualized by using the dye dihydroethidium on kidney cryosections (A). Superoxide (B) and DNA double strand break formation (C) in control rats, rats treated with gum arabic (15% w/v in drinking water) and rats treated with adenine (0.75% w/w) alone in feed, or with adenine and gum arabic given concomitantly at the same dose for 28 days.
Each column and vertical bar represents the mean ± SEM (n = 5). ** p## p<0.01, ### p<0.001 vs. adenine treatment.

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