Protective effect of panaxydol against repeated administration of aristolochic acid on renal function and lipid peroxidation products via activating Keap1‐Nrf2/ARE pathway in rat kidney

Guo, Yinxue; Hu, Maorong; Ma, Juan; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Shair, Omar H.M.; Ge, Pingyu

doi:10.1002/jbt.22619

Cited by 15 publications

(11 citation statements)

References 45 publications

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“…Finally, lipid peroxidation, one of the final responses of oxidation in CKD [ 40 , 41 ], was studied by staining for 4-HNE. A significant increase of lipid peroxidation was only observed in the kidneys of 18-month-old mice, but not at 12-months-old ( Figure 9 ).…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, NRF2 activation goes beyond cytoprotective properties, as it is implicated in lipid metabolism [ 67 ]. In CKD, aberrant quantities of plasma lipids are a target of ROS, creating subproducts such as 4-HNE, among others [ 40 ]. In our study, we only observed 4-HNE production at 18 months, suggesting an excess of ROS production and lipid deposition, not compensated by efficient antioxidant responses, as evidenced by low Cat and Sod-1 gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, Hmox1 mRNA levels were elevated in the kidneys from 18-month-old mice, but not at earlier time points (Figure 8). Finally, lipid peroxidation, one of the final responses of oxidation in CKD [40,41], was studied by staining for 4-HNE. A significant increase of lipid peroxidation was only observed in the kidneys of 18-month-old mice, but not at 12-months-old (Figure 9).…”

Section: A Progressive Redox Imbalance Is Established In the Aging Kidneymentioning

confidence: 99%

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Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

et al. 2022

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Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non-invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senescence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was observed by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, characterized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progression.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: A Progressive Redox Imbalance Is Established In the Aging Kidneymentioning

confidence: 99%

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Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

et al. 2022

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“…However, the degree of lung injury in mice pretreated with the ferroptosis inhibitor ferrostatin-1 was significantly improved, suggesting that ferroptosis plays an important role in the occurrence and development of ALI caused by MTB and LPS [51,52]. In addition, panaxydol can inhibit ferroptosis in ALI induced by LPS, and its effect is due to the upregulation of the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2/heme oxygenase-1 (HO-1) pathway [53,54]. Pseudomonas aeruginosa is an important pathogen that causes nosocomial infection.…”

Section: Infection-related Alimentioning

confidence: 99%

The role of ferroptosis in acute lung injury

2022

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common disease with high morbidity and mortality, and its pathogenesis is believed to be related to oxidative stress, apoptosis, inflammation, and hypoxia. Ferroptosis is a type of nonapoptotic cell death characterized by iron-dependent lipid peroxide accumulation and is involved in many cellular physiological processes. Recent studies have confirmed that ferroptosis may be involved in the development of ALI. This review summarizes the most recent discoveries on the role of ferroptosis in ALI to provide new strategies for its prevention and treatment. Keywords Ferroptosis • Glutathione peroxidase 4 • Lipid peroxidation • Acute lung injuryAcute lung injury/acute respiratory distress syndrome (ALI/ ARDS) is a common and critical disease caused by several factors, including infection, trauma, radiation, and ischemiareperfusion [1][2][3][4]. Although significant advancements have been achieved, such as mechanical ventilation and corticosteroid administration, the annual mortality of ALI remains 40% [5]. Thus, efforts to develop new targets that interrupt the progression of ALI to ARDS are an attractive endeavor. The pathogenesis of ALI was previously believed to involve oxidative stress, apoptosis, inflammation, and hypoxia [6][7][8].Recent studies have demonstrated that ferroptosis might be involved in the development of ALI [9]. In this review, the most recent discoveries regarding the role of ferroptosis in ALI are reviewed to provide new strategies for its prevention and treatment.

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“…The major characteristics of extensive tubulointerstitial fibrosis and the scar formation accompanied by renal tubular atrophy have been found in mouse and human AAN [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Recent studies have revealed that AAI causes severe a reduction in the capillaries around the renal tubules, leading to hypoxia and the death of the renal tubular epithelial cells [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Furthermore, AAI increased the expression of fibrotic cytokine transforming growth factor 1 (TGF-1) and connective tissue growth factor (CTGF), which enhance fibrosis and scar formation [ 5 , 6 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease

Chen

et al. 2021

Toxins

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Chronic kidney disease (CKD) is a commonly occurring complex renal syndrome that causes overall mortality in many diseases. The clinical manifestations of CKD include renal tubulointerstitial fibrosis and loss of renal function. Metallothionein-I/II (MT-I/II) is potentially expressed in the liver and kidney, and possesses antioxidant and metal detoxification properties. However, whether MT-I/II expression is associated with the prognosis of nephropathy remains unknown. In this study, we investigated the MT-I/II level in human CKD, using immunohistochemistry. MT-I/II is located on the proximal tubules and is notably reduced in patients with CKD. MT-I/II expression was significantly correlated with the functional and histological grades of CKD. In an aristolochic acid (AAI)-induced nephropathy mouse model, MT-I/II was abundantly increased after AAI injection for 7 days, but decreased subsequently compared to that induced in the acute phase when injected with AAI for 28 days. Furthermore, we found that ammonium pyrrolidinedithiocarbamate (PDTC) restored AAI-induced MT-I/II reduction in HK2 cells. The injection of PDTC ameliorated AAI-induced renal tubulointerstitial fibrosis and reduced the concentrations of blood urea nitrogen and creatinine in mouse sera. Taken together, our results indicate that MT-I/II reduction is associated with advanced CKD, and the retention of renal MT-I/II is a potential therapeutic strategy for CKD.

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Protective effect of panaxydol against repeated administration of aristolochic acid on renal function and lipid peroxidation products via activating Keap1‐Nrf2/ARE pathway in rat kidney

Cited by 15 publications

References 45 publications

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

The role of ferroptosis in acute lung injury

Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease

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