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

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.

Effect of Acacia gum on blood pressure in rats with adenine-induced chronic renal failure.

Chronic renal failure (CRF) occurring naturally in patients or induced by subtotal nephrectomy in rats induces several alterations in the cardiovascular system (CVS). However, the effect of chemically induced CRF in rats on the CVS is less well known. We induced CRF in rats by feeding adenine (0.75%, w/w, four weeks) and investigated the effect of the ensuing CRF on the systolic and diastolic blood pressure (BP) and heart rate (HR). Further, we investigated the effect of giving acacia gum (AG, 10%, w/v) in the drinking water concomitantly with adenine on the above parameters. AG has been previously shown to ameliorate the severity of CRF in humans and rats. We confirmed here that adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly increased both systolic and diastolic BP, with no significant effect on HR. Both of these actions were significantly mitigated by AG treatment. The antihypertensive angiotenisn-converting enzyme inhibitor lisinopril (10mg/kg) was given by gavage to rats concomitantly with adenine, significantly reduced the rise in blood pressure induced by adenine. In conclusion, adenine-induced CRF in rats significantly increased BP, and this was significantly mitigated by administration of AG. Possible mechanisms of these changes and the protective effect of AG will be investigated.

Motor and behavioral changes in rats with adenine-induced chronic renal failure: influence of acacia gum treatment.

Chronic renal failure (CRF) either occurring naturally in humans or induced surgically in rats causes alterations in behavior and motor functions. However, the effect of chemically induced CRF in rats on behavior is not known. We induced CRF in rats by feeding adenine (0.75% w/w, four weeks) and investigated the effect of the ensuing CRF on a depression model (forced swimming test, FST), analgesia (mechanical nociception), neuromuscular coordination (Rota-rod test) and motor activity (activity meter test). Further, we investigated the effect of giving acacia gum (AG, 10% w/v) in the drinking water concomitantly with adenine using the above models. AG has been previously shown to ameliorate the severity of CRF in humans and rats. Adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly reduced motor activity and increased immobility time in the FST, suggesting a depressant-like effect. Both of these actions were significantly antagonized by AG treatment. Adenine insignificantly reduced the mechanical nociceptive threshold by 15%. The results of the tests for neuromuscular coordination were inconclusive. In conclusion, adenine-induced CRF caused motor and behavioral alterations, and these were significantly mitigated by administration of AG.

Effects of Gum Arabic in rats with adenine-induced chronic renal failure.

Gum Arabic (GA [Acacia senegal]) is reputed, in Arabian medicinal practices, to be useful in treating patients with chronic renal failure (CRF), albeit without strong scientific evidence. We have previously shown that GA had no significant effect in rats with CRF induced by surgical nephrectomy. Here, we used another animal model of human CRF (feeding adenine at a concentration of 0.75%(w/w) for four weeks) to test the effect of GA on CRF. Renal morphology and measurements of plasma concentrations of urea and creatinine (Cr), and Cr clearance, in addition to urinary volume, osmolarity and protein concentrations, and N-acetylglucosamine and lactate dehydrogenase activities were performed. Interleukin-6 and the total antioxidant levels in urine, as well as the activity of superoxide dismutase in renal tissues, were estimated. Adenine feeding resulted in marked renal damage. GA (6%(w/v) and 12%(w/v) in drinking water for four consecutive weeks) significantly ameliorated the adverse biochemical alterations indicative of renal failure, abated the decrease in body weight and reduced the glomerular, tubular and interstitial lesions induced by adenine. Our study provides evidence that GA attenuated renal dysfunction in this model of CRF, suggesting a promising potential for it in protecting against renal failure progression. The mechanism(s) of this nephroprotection is uncertain but may involve anti-oxidant and/or anti-inflammatory actions.

Diesel exhaust particles in the lung aggravate experimental acute renal failure.

Inhaled particles are associated with pulmonary and extrapulmonary effects. Also, acute renal failure (ARF) is associated with increased mortality, related to pulmonary complications. Here, we tested the possible potentiating effect of diesel exhaust particles (DEP) in an animal model of ARF induced by a single ip injection of cisplatin (CP, 6 mg/kg) in rats. Six days later, the rats were intratracheally instilled with either DEP (0.5 or 1 mg/kg) or saline (control) and renal, systemic, and pulmonary variables were studied 24 h thereafter. CP increased the serum concentrations of urea and creatinine and reduced glutathione (GSH) concentration and superoxide dismutase activity in renal cortex. CP caused renal tubular necrosis; increased urine volume, protein concentrations, and N-acetyl-beta-D-glucosaminidase (NAG) activity; and decreased urine osmolality. The combination of DEP and CP aggravated the CP-induced effects on serum urea and creatinine, urine NAG activity, and renal GSH. The arterial O(2) saturation and PO(2) were significantly decreased in CP + DEP versus CP + saline and CP + DEP versus DEP. The number of platelets was reduced in DEP compared to saline-treated rats and CP + DEP versus DEP alone or CP + saline. Increases in macrophage and neutrophils numbers in bronchoalveolar lavage were found in DEP versus saline group and CP + DEP versus CP. Histopathological changes in lungs of DEP-treated rats were aggravated by the combination of CP + DEP. These included marked interstitial cell infiltration and congestion. We conclude that the presence of DEP in the lung aggravated the renal, pulmonary, and systemic effects of CP-induced ARF.