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.
Highlights
Chronic kidney disease (CKD) is a serious global health problem, and is considered a key determinant of the poor health outcomes of major noncommunicable diseases [1]
We have extended our previous observations on the effects of gum arabic (GA) treatment on rats with adenine–induced chronic renal failure (CRF) [21], by investigating the anti-inflammatory and antioxidant mechanisms related to the protective effect of GA on adenineinduced CRF, using several novel parameters such as IL-10, as well as the generation of reactive oxygen species and DNA strand breaks
Gum Arabic Ameliorates Adenine-induced Renal Failure In the CRF model used in the present study, adenine is given mixed with the feed at a concentration of 0.75%, w/w, for 4 weeks
Summary
Chronic kidney disease (CKD) is a serious global health problem, and is considered a key determinant of the poor health outcomes of major noncommunicable diseases [1]. Several factors influence the onset and progression of this CKD, such as obesity, hypertension and diabetes mellitus. Beyond these factors, there is evidence of a pathophysiological role for inflammation and oxidative stress in CKD and its complications [2]. There is evidence of a pathophysiological role for inflammation and oxidative stress in CKD and its complications [2] These two events are prominent features of CKD and its complications in humans [3,4,5,6,7]. Patients with CKD have high plasma concentrations of inflammatory mediators (such as CRP, tumor necrosis factor (TNF)-a and other cytokines) and several markers of oxidative stress [15,16]
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