Short-term oral gavage administration of adenine induces a model of fibrotic kidney disease in rats

Zhu, Chang; Doyle, Kelly; Nikkel, Arthur L.; Olsen, Lauren D.; Namovic, Marian T.; Salte, K.; Widomski, D. L.; Su, Zhi; Donnelly‐Roberts, Diana L.; Gopalakrishnan, Murali; McGaraughty, Steve

doi:10.1016/j.vascn.2018.04.003

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…At the end of study 1, mRNA expression levels of genes associated with kidney inflammation and fibrosis (32,46) were higher in the HS group than in the NS group: Timp1 (4.8-fold), Acta2 (1.9-fold), Col3a1 (2.9-fold), Il6 (2.8-fold), Nfkb1 (1.5fold), Tnfa (2.0-fold), Mcp1 (2.2-fold), Vcam1 (1.6-fold), and Icam1 (1.9-fold; Fig. 7).…”

Section: Effect Of Praliciguat On Renal Function and Fibrosis (Studies 1 And 2)mentioning

confidence: 99%

Soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure

Shea

Price

Liu

et al. 2020

American Journal of Physiology-Renal Physiology

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Reduced nitric oxide (NO) and a decrease in cGMP signaling mediated by soluble guanylate cyclase (sGC) has been linked to the development of several cardiorenal diseases. Stimulation of sGC is a potential means for enhancing cGMP production in conditions of reduced NO bioavailability. The purpose of our studies was to determine the effects of praliciguat, a clinical-stage sGC stimulator, in a model of cardiorenal failure. Dahl salt-sensitive rats fed a high-salt diet to induce hypertension and organ damage were treated with the sGC stimulator praliciguat to determine its effects on hemodynamics, biomarkers of inflammation, fibrosis, tissue function, and organ damage. Praliciguat treatment reduced blood pressure, improved cardiorenal damage, and attenuated the increase in circulating markers of inflammation and fibrosis. Notably, praliciguat affected markers of renal damage at a dose that had minimal effect on blood pressure. In addition, liver fibrosis and circulating markers of tissue damage were attenuated in praliciguat-treated rats. Stimulation of the NO-sGC-cGMP pathway by praliciguat attenuated or normalized indicators of chronic inflammation, fibrosis, and tissue dysfunction in the Dahl salt-sensitive rat model. Stimulation of sGC by praliciguat may present an effective mechanism for treating diseases linked to NO deficiency, particularly those associated with cardiac and renal failure. Praliciguat is currently being evaluated in patients with diabetic nephropathy and heart failure with preserved ejection fraction.

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Section: Effect Of Praliciguat On Renal Function and Fibrosis (Studies 1 And 2)mentioning

confidence: 99%

Soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure

Shea

Price

Liu

et al. 2020

American Journal of Physiology-Renal Physiology

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“…Purine bases guanine (G) and adenine (A) are helpful biomarkers for a variety of medical conditions such as immune disorders, metabolic disorders, hearing and vision disorders, hyperuricosuria, neurological disorders, and arthritis. − The presence of G and A in physiological fluids might be attributed to nucleic acid metabolism via tissue breakdown or nutritional intake, or to enzyme deficiency in other metabolic pathways . Adenine is involved in a variety of critical actions, including heredity and metabolism. , Its metabolic faults can cause a variety of catastrophic disorders, including arthritis, cardiovascular disease, mental retardation, toxemia, and kidney failure. , Furthermore, this nitrogenous base not only contributes to the storage of genetic information, but it is also involved in a variety of biological mechanisms such as control of metabolic enzyme activities, cell signaling, and system energy transmission . Adenine concentration abnormalities in human systems have been linked to AIDS, renal illness, cancer, Parkinson’s disease, and a variety of other disorders that disrupt the metabolic pathways of this molecule. − Consequently, it is critical to develop a speedy and sensitive analytical method for determining and quantifying the concentration of adenine for clinical diagnostic purposes.…”

Section: Resultsmentioning

confidence: 99%

“…61,62 Its metabolic faults can cause a variety of catastrophic disorders, including arthritis, cardiovascular disease, mental retardation, toxemia, and kidney failure. 63,64 Furthermore, this nitrogenous base not only contributes to the storage of genetic information, but it is also involved in a variety of biological mechanisms such as control of metabolic enzyme activities, cell signaling, and system energy transmission. 65 Adenine concentration abnormalities in human systems have been linked to AIDS, renal illness, cancer, Parkinson's disease, and a variety of other disorders that disrupt the metabolic pathways of this molecule.…”

Section: ■ Introductionmentioning

confidence: 99%

Direct Metal-Free Synthesis of Uracil- and Pentaazaphenalene-Functionalized Porous Organic Polymers via Quadruple Mannich Cyclization and Their Nucleobase Recognition Activities

et al. 2022

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The development of new interconnections and synthetic approaches for the formation of porous organic polymers (POPs) is a challenging endeavor. Herein, we report a facile gramscale approach for the synthesis of uracil-and pentaazaphenalenefunctionalized porous organic polymers (Ur-POPs), namely, Ur-TPA, Ur-TPB, Ur-TPP, and Ur-TPT POPs, through a one-pot quadruple Mannich polycondensation of 6-aminouracil with paraformaldehyde and triamine linkers having various degrees of planarity, without the need for any additives such as templates and catalysts. Interestingly, the obtained Ur-POPs exhibited a uniform rod-like morphology, and depending on the planarity of the triamine linkers, a diameter variety of the rod was observed. These Ur-POPs possessed high specific surface areas, as high as 360 m 2 g −1 , and high thermal stability. In addition, the presence of uracil units in the primary skeleton of Ur-POPs combined with their regular rod-like structures endowed them with superior capabilities for remarkable selective recognition toward adenine in an aqueous solution.

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“…Following one week of acclimatization, rats (n = 48) were randomly divided into eight equal groups (n = 6 per group) and treated for 33 consecutive days. Flaxseed was mixed with the diet at a concentration of 15% w/w as described before [ 22 ]. The details of the treatments of the different groups are summarized in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Effect of flaxseed on systemic inflammation and oxidative stress in diabetic rats with or without chronic kidney disease

Za’abi

Ali

2021

PLoS ONE

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Background Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine–induced CKD. Methods Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. Results Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1β and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination. Conclusion These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.

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Short-term oral gavage administration of adenine induces a model of fibrotic kidney disease in rats

Cited by 10 publications

References 22 publications

Soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure

Soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure

Direct Metal-Free Synthesis of Uracil- and Pentaazaphenalene-Functionalized Porous Organic Polymers via Quadruple Mannich Cyclization and Their Nucleobase Recognition Activities

Effect of flaxseed on systemic inflammation and oxidative stress in diabetic rats with or without chronic kidney disease

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