Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute Nephrotoxicity through the NF-κB-Mediated Inflammation and PI3K/Akt/Apoptosis Signaling Pathways

Zhang, Weizhe; Hou, Jingang; Yan, Xiaohai; Leng, Jing; Li, Rongyan; Zhang, Jing; Xing, Jingjing; Chen, Chen; Wang, Zi; Li, Wei

doi:10.3390/nu10091328

Cited by 47 publications

(37 citation statements)

References 51 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the results of histopathological examination and Tunel assay revealed that cP aggravated kidney damage compared with the con group. The present results were consistent with those from previous studies (38). In the present study, Dex administration significantly inhibited the production of serum Bun and Scr and reversed the alterations in body weight and ri.…”

Section: Discussionsupporting

confidence: 94%

“…However, treatment with cP + dex + atip had a similar effect to cP alone; the expression levels of p-PI3K and p-AKT were significantly decreased in the cP + dex + atip group, indicating that the effects of dex were partially blocked by the α2ar antagonist. Furthermore, a previous study reported that aKT signaling is critical for recovery from renal ischemia-reperfusion injury, and that dex activates aKT via α2ar-dependent and -independent Pi3K coupling (38). Similarly, dex exerts neuroprotective (46), cardioprotective (28) and lung-protective effects (30,47) via activation of the Pi3K/aKT signaling pathway.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

View full text Add to dashboard Cite

cisplatin (cP) is an effective antineoplastic agent; however, cP-induced acute kidney injury (aKi) seriously affects the prognosis of patients with cancer. endoplasmic reticulum (er) stress (erS)-induced apoptosis serves a pivotal role in the pathogenesis of cP-induced aKi. dexmedetomidine (dex), a potent α 2 adrenergic agonist, has been reported to exert protective effects against aKi. However, the protective effects of dex against cP-induced aKi and the potential molecular mechanisms remain unknown. in the present study, male Sprague-dawley rats were divided into four groups (n=10/group), as follows: control group; cP group, rats received an intraperitoneal (i.p.) injection of 5 mg/kg cP; dex + cP group, rats received an i.p. injection of 25 µg/kg dex immediately after cP treatment; and dex + cP + atipamezole (atip) group, rats received an i.p. injection of 250 µg/kg atip, an α 2 adrenoreceptor (α 2 ar) antagonist, and then received the same treatment as the dex + cP group. rats were anesthetized and sacrificed 96 h after CP injection. Subsequently, serum blood urea nitrogen (Bun) and serum creatinine (Scr) were analyzed, and kidney samples were collected for analyses. Pathological changes were examined using hematoxylin and eosin staining, and protein expression levels were assessed using western blotting and immunohistochemical staining. in addition, apoptosis was examined using a terminal deoxynucleotidyl transferase duTP nick-end labeling assay. The present results suggested that dex protected against cP-induced aKi by attenuating histological changes in the kidney, serum Bun and Scr production. Furthermore, the expression levels of 78-kda glucose-regulated protein, c/eBP homologous protein and caspase-12, and the apoptotic rate in the kidney were decreased following dex treatment. in addition, the expression levels of phosphorylated (p)-Pi3K and p-aKT in the dex + cP group were significantly increased. Conversely, the renoprotective effects of dex were attenuated following the addition of atip. in conclusion, dex may alleviate cP-induced aKi by attenuating erS-induced apoptosis, at least in part, via the α 2 ar/Pi3K/aKT signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 96%

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…Determinations of nuclear factor‐κB (NF‐κB), IL‐1β, and TNF‐α were performed using kidney homogenate with the aid of specific ELISA kits (Diaclone Research, France) as per the guidelines of the manufacturer .…”

Section: Methodsmentioning

confidence: 81%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

View full text Add to dashboard Cite

In kidneys, elevated levels of inflammatory cytokines and oxidative stress were observed in nephrotoxicity triggered by cisplatin. Embelin has the anti-inflammatory property. It also got anti-tumorigenic and antioxidant properties. In this research, we analyzed the actions of embelin on nephrotoxicity triggered by cisplatin and vital actions by which it increases antioxidant actions and corrects the inflammation after embelin administration during nephrotoxicity triggered by cisplatin. Kidney function markers including blood urea nitrogen; serum creatinine; the markers of oxidative stress like malondialdehyde (MDA), antioxidant systems like glutathione, superoxide dismutase, glutathione S-transferase, catalase, and glutathione reductase; inflammation markers like nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β); and the extent of nuclear factor-erythroid-2 p45-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were determined. Histopathology studies of kidneys were also used to analyze nephrotoxicity induced by cisplatin. Treatment with embelin (25 and 50 mg/kg) upgrades the function of kidneys, by elevating antioxidant levels and reducing the MDA level in cisplatin-administered rats. Embelin treatment demonstrated a significant curtailment of oxidative stress as well as increased the activities of antioxidant enzymes, endogenously. Cisplatin upregulates cytokines (i.e., TNF-α and IL-1β) and NF-κB, and downregulates Nrf2 and HO-1. Embelin treatment also reduced the infiltration of neutrophils in the renal tubules and thus reduced the level of histological impairment. The outcome of this study implements that the signaling pathway of Nrf2/HO-1 may be the principal mechanism of embelin for protection from nephrotoxicity triggered by cisplatin, and thus, embelin diminishes oxidative stress and inflammation by impeding NF-κB.

show abstract

“…Natural compounds from herbs or medicinal plants are widely used for therapy and prevention of kidney diseases 16,17 . Ginseng, the root of Panax ginseng C.A.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of ginsenoside Rk1, a major rare saponin from black ginseng, on cisplatin‐induced nephrotoxicity in HEK‐293 cells

Jiang

et al. 2020

The Kaohsiung J of Med Scie

Self Cite

View full text Add to dashboard Cite

Cisplatin, as one of the most effective chemotherapeutic agents, its clinical use is limited by serious side effect of nephrotoxicity. Cisplatin‐induced nephrotoxicity is closely related to apoptosis induction and activation of caspase. The present study aimed to explore the potential protective effect of ginsenoside Rk1 (Rk1), a rare ginsenoside generated during steaming ginseng, on cisplatin‐induced nephrotoxicity and the underlying mechanisms in human embryonic kidney 293 (HEK‐293) cells. Our results showed that the reduced cell viability induced by cisplatin could significantly recover by Rk1. Furthermore, glutathione (GSH) as an oxidative index, was elevated and the lipid peroxidation product malondialdehyde (MDA) was significantly decreased after Rk1 treatment compared to the cisplatin group. Additionally, Rk1 can also decrease the ROS fluorescence expression and increase the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) compared to the cisplatin group, which suggested a suppression of oxidative response. More importantly, the cisplatin‐induced elevated protein levels of Bax, cleaved caspase‐3, cleaved caspase‐9, and decreased protein level of Bcl‐2 were reversed after treatment with Rk1. Our results elucidated the possible protective mechanism of Rk1 for the first time, which may involve in its anti‐oxidation and anti‐apoptosis effects.

show abstract

Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute Nephrotoxicity through the NF-κB-Mediated Inflammation and PI3K/Akt/Apoptosis Signaling Pathways

Cited by 47 publications

References 51 publications

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Protective effect of ginsenoside Rk1, a major rare saponin from black ginseng, on cisplatin‐induced nephrotoxicity in HEK‐293 cells

Contact Info

Product

Resources

About