Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway

Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Yanhan; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

doi:10.1016/j.tox.2014.01.008

Cited by 62 publications

(47 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in the case of resveratrol, human studies are currently ongoing. Another NRF-2 activator, bardoxolone methyl, was shown to successfully improve kidney function during AKI and CKD in both animals and humans (113,229,325). However, a phase 3 study, in which bardoxolone methyl was administered to patients with kidney disease, was recently discontinued due to the high toxicity of the drug and an associated increase in mortality.…”

Section: Naturally Occurring Antioxidantsmentioning

confidence: 99%

Oxidant Mechanisms in Renal Injury and Disease

Ratliff

Abdulmahdi

Pawar

et al. 2016

Antioxidants & Redox Signaling

537

513

View full text Add to dashboard Cite

Significance: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/ disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. Recent Advances: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/ RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. Critical Issues: The review summarizes the critical sources of oxidative stress in the kidney during injury/ disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules. Future Directions: Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones.

show abstract

Section: Naturally Occurring Antioxidantsmentioning

confidence: 99%

Oxidant Mechanisms in Renal Injury and Disease

Ratliff

Abdulmahdi

Pawar

et al. 2016

Antioxidants & Redox Signaling

537

513

View full text Add to dashboard Cite

show abstract

“…37 Pharmacologic Nrf2 activation also improved aristolocholic acid-induced AKI in mice. 38 Because persistent oxidant stress is a feature of AKI models leading to fibrosis, pharmacologic Nrf2 activation is theoretically a promising approach to attenuate the AKI to CKD transition.…”

Section: Question 3 What Are the Relevant Biochemical Pathways Relatmentioning

confidence: 99%

Progression after AKI

Basile

Bonventre

Mehta

et al. 2016

Journal of the American Society of Nephrology

368

298

View full text Add to dashboard Cite

Recent clinical studies indicate a strong link between AKI and progression of CKD. The increasing prevalence of AKI must compel the nephrology community to consider the long-term ramifications of this syndrome. Considerable gaps in knowledge exist regarding the connection between AKI and CKD. The 13th Acute Dialysis Quality Initiative meeting entitled "Therapeutic Targets of Human Acute Kidney Injury: Harmonizing Human and Experimental Animal Acute Kidney Injury" convened in April of 2014 and assigned a working group to focus on issues related to progression after AKI. This article provides a summary of the key conclusions and recommendations of the group, including an emphasis on terminology related to injury and repair processes for both clinical and preclinical studies, elucidation of pathophysiologic alterations of AKI, identification of potential treatment strategies, identification of patients predisposed to progression, and potential management strategies.

show abstract

“…Mice in the treatment group were one of the groups fed a HF diet for 21 weeks, which also received an oral daily dose of BM (10 mg/kg) in their drinking water. We chose the BM dose according to a previous study (Wu et al , 2014). Body weight was measured weekly for the duration of the experiment (Final average body weight after 21 weeks: LC, 27.15g; HF, 40.84g; HF+BM, 28.13g).…”

Section: Animals and Hf Diet-induced Obesity Modelmentioning

confidence: 99%

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Camer

Szabo

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

X. (2015). Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 59 68-75. Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory AbstractHigh fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood-brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF dietinduced impairment in recognition memory (p < 0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p < 0.05), however, no changes were seen in the hippocampus (p > 0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p < 0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus. AbstractHigh-fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), HF (40% of energy as fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p<0.05). BM a...

show abstract

Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway

Cited by 62 publications

References 42 publications

Oxidant Mechanisms in Renal Injury and Disease

Oxidant Mechanisms in Renal Injury and Disease

Progression after AKI

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Contact Info

Product

Resources

About