Adenine‐induced chronic kidney disease in rats

Diwan, Vishal; Brown, Lindsay; Gobé, Glenda C.

doi:10.1111/nep.13180

Cited by 191 publications

(166 citation statements)

References 56 publications

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“…The validity of feeding adenine as a rodent model for human CKD has been confirmed before by several authors [10]. Recently a new model of CKD, using spontaneously diabetic Torii rats has been reported, and was found to be particularly useful in CKD with mineral bone disorder [35].…”

Section: Discussionmentioning

confidence: 62%

Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease

Za’abi

Al-Salam

Suleimani

et al. 2018

Cell Physiol Biochem

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Background/Aims: The effect of treatment with gum acacia (GA), a prebiotic shown previously to ameliorate chronic kidney disease (CKD), in diabetic and non – diabetic rats with adenine – induced CKD has been investigated using several conventional and novel physiological, biochemical, and histopathological parameters. Methods: Diabetes mellitus was induced in rats by a single injection of streptozotocin (STZ). Diabetic and non – diabetic rats were randomly divided into several groups, and given either normal food or food mixed with adenine (0.25% w/w, for five weeks) to induce CKD. Some of these groups were also concomitantly treated orally with GA in the drinking water (15% w/w). Results: Rats fed adenine alone exhibited physiological (decreased body weight, increased food and water intake and urine output), biochemical (increase in urinary albumin/creatinine ratio, plasma urea and, creatinine, indoxyl sulfate and phosphorus), inflammatory biomarkers (increased in neutrophil gelatinase-associated lipocalin, transforming growth factor beta -1, tumor necrosis factor alpha, adiponectin, cystatin C and interleukin-1β), oxidative biomarkers (8-isoprostane, 8 -hydroxy -2-deoxy guanosine), nitrosative stress biomarkers (nitrite and nitrate) and histopathological (increase in tubular necrosis and fibrosis) signs of CKD. STZ - induced diabetes alone worsened most of the renal function tests measured. Administration of adenine in STZ – diabetic rats further worsened the renal damage induced by adenine alone. GA significantly ameliorated the renal actions of adenine and STZ, given either singly or in combination, especially with regards to the histopathological damage. Conclusion: GA is a useful dietary agent in attenuating the progression of CKD in rats with streptozotocin-induced diabetes.

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Section: Discussionmentioning

confidence: 62%

Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease

Za’abi

Al-Salam

Suleimani

et al. 2018

Cell Physiol Biochem

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“…In conclusion, in this work we show that the limited time slot and overall induced toxicity dramatically limits the feasibility to deploy AAI as a chemical to set-up a renal fibrosis model in zebrafish. However, it can be expected that other renal fibrogenic compounds like adenine or folic acid [5,6] with substantially lower systemic toxicity could offer advantages over AAI, and further experimental work exploring the renal fibrogenic potential of these compounds in tert −/− but possibly also in wild type (WT) zebrafish is warranted.…”

Section: Discussionmentioning

confidence: 99%

“…These include TGFb1-induced in vitro fibrosis models [2] and in vivo CKD models such as the TGFb1 overexpressing mice model [3] and the unilateral ureteral obstruction (UUO) model [4]. In addition, also chemically-induced models based on the chronic treatment of rodents with compounds like adenine [5], folic acid [6], and aristolochic acid [7,8] have been used. Aristolochic acid (AA)-induced nephropathy in humans is characterized by progressive renal interstitial fibrosis leading to ESRD and urothelial malignancy and has been observed after unintentional oral intake of Aristolochia species [9].…”

Section: Introductionmentioning

confidence: 99%

Nephrotoxic Effects in Zebrafish after Prolonged Exposure to Aristolochic Acid

Wang

Giusti

et al. 2020

Toxins

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With the aim to explore the possibility to generate a zebrafish model of renal fibrosis, in this study the fibrogenic renal effect of aristolochic acid I (AAI) after immersion was assessed. This compound is highly nephrotoxic able to elicit renal fibrosis after exposure of rats and humans. Our results reveal that larval zebrafish at 15 days dpf (days post-fertilization) exposed for 8 days to 0.5 µM AAI showed clear signs of AKI (acute kidney injury). The damage resulted in the relative loss of the functional glomerular filtration barrier. Conversely, we did not observe any deposition of collagen, nor could we immunodetect α-SMA, a hallmark of myofibroblasts, in the tubules. In addition, no increase in gene expression of fibrogenesis biomarkers after whole animal RNA extraction was found. As zebrafish have a high capability for tissue regeneration possibly impeding fibrogenic processes, we also used a tert−/− zebrafish line exhibiting telomerase deficiency and impaired tissue homeostasis. AAI-treated tert−/− larvae displayed an increased sensitivity towards 0.5 µM AAI. Importantly, after AAI treatment a mild collagen deposition could be found in the tubules. The outcome implies that sustained AKI induced by nephrotoxic compounds combined with defective tert−/− stem cells can produce a fibrotic response.

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“…As most rodent models for CKD have studied male animals only [11], we focused on this sex, expecting more homogenous and pronounced effects. Frequently used rat CKD models are induced by ureteral obstruction, ischemia/reperfusion injury, or subtotal 5/6 nephrectomy.…”

Section: Discussionmentioning

confidence: 99%

A Novel Model of Chronic Kidney Disease in Rats: Dietary Adenine in Combination with Unilateral Nephrectomy

et al. 2019

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Background: Adenine at 0.75% in the diet (AD) triggers renal impairment in rats. This model of kidney disease is largely reversible when AD feeding is stopped. Testing of novel drugs parallel to AD administration may result in unwanted interference. Objectives: We hypothesized that combining AD with unilateral nephrectomy (UNx) would result in progressive chronic kidney disease (CKD) even after cessation of AD. Methods: In an explorative study, 16 rats with UNx (AD-1K rats) and 10 sham-operated rats (AD-2K rats) received AD-supplemented feed for 3 weeks, followed by 4 weeks of standard chow. Ten sham-operated rats receiving only standard chow served as controls. Laboratory parameters in blood and urine were frequently assessed during and after cessation of AD feeding. Comprehensive pathological examinations were performed in all rats at the end of the experiment. Results: Rats with UNx were more affected by impaired glomerular filtration rate, anemia, hyperphosphatemia, and hypocalcemia. After cessation of AD feeding, recovery was poorest in AD-1K rats, paralleled by increased proteinuria indicative of progressive CKD. Scores in histopathological damage of the kidneys indicative of CKD were seen in both AD-fed groups, with key parameters being more affected in AD-1K rats. Histopathological changes in the heart were most prominent in AD-1K rats. Conclusions: Combining AD feeding with UNx provides a time window after cessation of AD feeding for the testing of drugs without interference. Our findings in rats may have implications for research in other target animal species as well.

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Adenine‐induced chronic kidney disease in rats

Abstract: Summary at a Glance This invited review article describes the adenine model of chronic kidney disease in rodents and compares its features with other rodent models of kidney disease.

Cited by 191 publications

References 56 publications

Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease

Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease

Nephrotoxic Effects in Zebrafish after Prolonged Exposure to Aristolochic Acid

A Novel Model of Chronic Kidney Disease in Rats: Dietary Adenine in Combination with Unilateral Nephrectomy

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