Aishwarya Ramkumar

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.

The effect of activated charcoal on adenine-induced chronic renal failure in rats.

Activated charcoal (AC) is a sorbent that has been shown to remove urinary toxins like urea and indoxyl sulfate. Here, the influence of AC on kidney function of rats with experimental chronic renal failure (CRF) is investigated. CRF was induced in rats by feeding adenine (0.75%) for four weeks. As an intervention, AC was added to the feed at concentrations of 10%, 15% or 20%. Adenine treatment impaired kidney function: it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and vanin-1. Furthermore, it raised plasma concentrations of the uremic toxins indoxyl sulfate, phosphate and uric acid. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activity, total antioxidant capacity and reduced glutathione were adversely affected. Most of these changes were significantly ameliorated by dietary administration of AC at a concentration of 20%, while effects induced by lower doses of dietary AC on adenine nephrotoxicity were not statistically significant. The results suggest that charcoal is a useful sorbent agent in dietary adenine-induced CRF in rats and that its usability as a nephroprotective agent in human kidney disease should be studied.

Renal and myocardial histopathology and morphometry in rats with adenine - induced chronic renal failure: influence of gum acacia.

Background/Aim: Chronic kidney disease (CKD) is associated with increased occurrence of cardiovascular system dysfunction. Previous studies have revealed a number of alterations in the kidneys and heart during CKD. However, unbiased quantitative studies on these structures in this disease have so far not been addressed. Materials and Methods: We induced CKD in rats by feeding adenine (0.75% w/w, four weeks) and using unbiased stereological methods, investigated the effect of the ensuing CKD on the kidneys and left ventricular structure. Since gum acacia (GA) has previously been shown to ameliorate the severity of CKD in humans and rodents, we investigated the effect of giving GA (15% w/v in the drinking water concomitantly with adenine) on the kidneys and left ventricular structure using the above model. Results: The CKD was confirmed by standard biochemical indices in plasma and urine and by accumulation of the uremic toxin indoxyl sulfate. Additionally, it increased blood pressure. In rats with CKD absolute volume of left ventricle was significantly increased, and the volume density and absolute volume of myocardial capillaries were decreased, whilst the same parameters of myocardium and interstitial tissue were increased. Renal morphometry demonstrated significant increase in kidney volume and interstitial tissue in adenine- treated rats. Similarly, glomerular Bowmans capsule was significantly thickened. The myocardial and renal changes were significantly mitigated by GA treatment. Conclusions: These results add to our existing knowledge of the pathophysiology of adenine - CKD and provides plausible histopathological and morphometric evidence for the usefulness of GA in CKD.

Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine-induced chronic kidney disease

The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine‐induced chronic kidney disease (CKD) model.

Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia

Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation.

Some physiological and histological aspects of the gastrointestinal tract in a mouse model of chronic renal failure.

INTRODUCTION It has been reported that mice with 5/6 nephrectomy- induced chronic renal failure (CRF) have reduced gastrointestinal transit (GIT) and increased fecal moisture content (FMC). We have recently shown that feeding adenine (0.2%, w/w) to mice can be used as a model of CRF. Here, we investigated the possible effects of adenine-induced CRF on several in vivo and in vitro aspects of GIT physiology and histology of the stomach, duodenum, ileum and colon in mice. METHODS The effects of CRF induced by feeding adenine (0.2%, w/w for 2 or 4 weeks) on the gastric emptying index (GEI), GIT, FMC and bead expulsion test (BET) were investigated. GIT was measured by the charcoal meal test and GEI by the difference between full and empty stomach weights. Fresh and dried feces were weighed to calculate the FMC. Renal function was assessed histologically, and biochemically in plasma and urine. The light microscopic histology of the different parts of the gut, as well as the in vitro contractility of the isolated ileum was also assessed. RESULTS Feeding adenine for 2 or 4 weeks resulted in CRF. The BET was significantly increased in mice given adenine for 2 but not 4 weeks, while the GEI was significantly increased in mice treated with adenine for 4 but not 2 weeks. No significant differences between control and adenine-treated mice were found in GIT, FMC or the histology of the different parts of the gut. Acetylcholine-induced contractions of the ileum of adenine-treated rats were not significantly different from those of the controls. DISCUSSION Feeding adenine for either 2 or 4 weeks resulted in CRF, but it would appear that this model produces effects on the gastrointestinal tract that are milder than those reported before in animal models with 5/6 nephrectomy-induced-CRF.

Fish Waste-Potential Low Cost Substrate for Bacterial Protease Production: A Brief Review

Industrial biotechnology processes have recently been exploited for an economic utilization of wastes to produce value added products. Of which, fish waste is one of the rich sources of proteins that can be utilized as low cost substrates for microbial enzyme production. Fish heads, tails, fins, viscera and the chitinous materials make up the wastes from fish industries. Processing these wastes for the production of commercial value added products could result in a decrease in the cost of production. In addition, we can eliminate the pollution of the environment and health issues due to the improper disposal of these fish wastes. This review highlights the potential use of fish waste as a cheaper substrate for the production of economically important protease enzyme.

Production of thermotolerant, detergent stable alkaline protease using the gut waste of Sardinella longiceps as a substrate: Optimization and characterization

The gut wastes of Sardinella longiceps were used as substrate for protease production. The gut waste has 61.6% proteins, 21.8% lipids, 8.5% carbohydrates on dry weight basis and trace elements. The significant factors of protease fermentation were screened by Plackett-Burman design. A protease activity of 68.56 U/ml was predicted at 46.31 °C, incubation time 71.11 h, inoculum 4.86% (v/v) and substrate concentration 2.66% (w/v), using response surface methodology. However, the validation experiment showed 73.52 U/ml activity. The artificial neural network was found as a better tool to predict the experimental results. The partially purified protease showed higher activity at pH 9 and 10 and retained 90% activity after 120 h at pH 9. It showed maximum activity at 50 °C and retained 88% residual activity until 90 min at 50 °C. Zn++ enhanced the protease activity by 40%. The protease retained an activity of 93, 103, 90 and 98% against urea, β-mercaptoethanol, SDS and tween 80 respectively. The alkaline protease was compatible with all the commercial detergents tested with the residual activity above 90%. The alkaline protease exhibited 22% higher activity on the tryptone soya substrate. The gut waste of S. longiceps is a worthy low cost substrate for the production of industrially important alkaline protease.