New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: comparison with rats.

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.

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 Hibiscus sabdariffa and its anthocyanins on some reproductive aspects in rats.

An aqueous extract of Hibiscus sabdariffa L. is a common beverage in many parts of the world. Reports on its effect on reproduction are conflicting, with anecdotal evidence that the plant is an aphrodisiac, while others report that it is estrogenic, and adversely affects spermatogenesis in rats. We have studied the effect of different concentrations of aqueous extracts of H. sabdariffa calyces (10%, 15% and 20%) used as drinking water for 10 consecutive weeks, and its anthocyanins (50, 100, 200 mg/kg for 5 days, orally) on the weight and histology of the testis, and on some biochemical constituents in testicular homogenates, in addition to the plasma concentrations of testosterone, luteinizing hormone and estradiol. The possible presence of an estrogenic effect of the extract and anthocyanins on the uteri of immature female rats was also tested. Neither the H. sabdariffa extract nor the anthocyanins significantly altered either testicular weight and histology, or uterus weight. Plasma concentrations of the three hormones studied, the testicular concentrations of protein, reduced glutathione and total cholesterol, and superoxide dismutase activity were all insignificantly affected by either the extract or the anthocyanins, except for a slight, but statistically significant, decrease in testicular protein concentration caused by the 15% aqueous extract when compared with controls. These results suggest that H. sabdariffa exerts no adverse effect on the male reproductive system. Consumption of H. sabdariffa aqueous extract inhibited the growth of the rats compared with the controls.

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.