Protective Effects of 6-Shogaol, an Active Compound of Ginger, in a Murine Model of Cisplatin-Induced Acute Kidney Injury

Gwon, Mi‐Gyeong; Gu, Hyemin; Leem, Jaechan; Park, Kwan‐Kyu

doi:10.3390/molecules26195931

Cited by 27 publications

(27 citation statements)

References 57 publications

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“…In the present study, administration of oridonin decreased the amounts of 4-HNE and MDA in kidneys of cisplatin-injected mice. These molecules are well-known lipid peroxidation products and have been shown to be increased in cisplatin nephrotoxicity [ 34 , 35 ]. Moreover, cisplatin injection lowered the GSH/GSSG ratio, indicating increased oxidative stress [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice

Gwon

Kim

et al. 2022

BioMed Research International

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The use of cisplatin, a chemotherapy drug, is often limited due to its renal side effects such as acute kidney injury (AKI). However, there are no validated medications to prevent or treat cisplatin-induced AKI. Oridonin is the major bioactive component of Isodon rubescens (Rabdosia rubescens) and exhibits anticancer, antioxidative, and anti-inflammatory effects. Recent studies have shown that oridonin alleviated a variety of inflammatory diseases, including renal diseases, in rodents. This study was aimed at investigating the potential renoprotective effect of oridonin on cisplatin-induced AKI. Male C57BL/6 mice were administered with cisplatin (20 mg/kg) with or without oridonin (15 mg/kg). Oridonin administration to mice after cisplatin injection attenuated renal dysfunction and histopathological changes. Upregulation of tubular injury markers was also suppressed by oridonin. Mechanistically, oridonin suppressed lipid peroxidation and reversed the decreased ratio of reduced to oxidized glutathione in cisplatin-injected mice. The increase in cisplatin-induced apoptosis was also alleviated by the compound. Moreover, oridonin inhibited cytokine overproduction and attenuated immune cell infiltration in cisplatin-injected mice. Altogether, these data demonstrated that oridonin alleviates cisplatin-induced kidney injury via inhibiting oxidative stress, apoptosis, and inflammation.

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Section: Discussionmentioning

confidence: 99%

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice

Gwon

Kim

et al. 2022

BioMed Research International

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“…To assess renal function, the serum concentrations of creatinine and blood urea nitrogen (BUN), two widely used indicators of kidney function [ 25 ], were measured. As shown in Figure 1 A,B, hispidulin administration significantly decreased the serum levels of creatinine (LPS, 0.80 ± 0.07 mg/dL vs. LPS + His, 0.52 ± 0.05 mg/dL, p < 0.01) and BUN (LPS, 120.8 ± 13.5 mg/dL vs. LPS + His, 71.1 ± 9.6 mg/dL, p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

“…Serum creatinine and BUN levels were measured to assess kidney function. These indicators are widely used in animal experiments to evaluate kidney function [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. We found that hispidulin significantly attenuated the LPS-induced renal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

Kim

Leem

2022

Molecules

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Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death.

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“…However, the LPS-induced neutrophil infiltration was inhibited by carnosic acid (p < 0.001; Figure 5A,B). We also performed IHC staining for F4/80, a macrophage marker [23], on kidney sections to examine macrophage infiltration into the kidney. The number of F4/80-positive cells was increased after LPS injection, which was reduced by carnosic acid (p < 0.05; Figure 5C,D).…”

Section: Carnosic Acid Attenuated Lps-induced Inflammatory Responsesmentioning

confidence: 99%

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

et al. 2021

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Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

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Protective Effects of 6-Shogaol, an Active Compound of Ginger, in a Murine Model of Cisplatin-Induced Acute Kidney Injury

Cited by 27 publications

References 57 publications

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice

Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

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