Saikosaponin-D reduces cisplatin-induced nephrotoxicity by repressing ROS-mediated activation of MAPK and NF-κB signalling pathways

Ma, Xiaolong; Dang, Chengxue; Kang, Huafeng; Dai, Zhijun; Lin, Shuai; Guan, Huaijin; Liu, Xiaoxu; Wang, Xijing; Hui, Wentao

doi:10.1016/j.intimp.2015.06.020

Cited by 98 publications

(58 citation statements)

References 42 publications

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“…Oxidative stress is caused by a range of oxygen‐derived free radicals (ROS), including superoxide anion, hydrogen peroxide and hydroxyl radical. Excessive production of these free radicals and lipid peroxidation, as have been found in CDDP‐induced renal dysfunction (Chirino et al , ), can activate many pro‐inflammatory cytokine responses and cause irreversible renal damage (Ma et al , ).…”

Section: Introductionmentioning

confidence: 99%

“…Sirt1 is involved in diverse biological processes including metabolism, oxidative stress and inflammation by deacetylation of some genes including those for NF‐κB, FOXO3, p53 and histones (Luo et al , ; Vaziri et al , ; Motta et al , ; Yeung et al , ). Sirt1 can lead to the rapid activation of NF‐κB associated with CDDP‐induced renal inflammation through increasing the levels of pro‐inflammatory cytokines and inflammatory mediators including IL‐1β, IL‐6 and TNF‐α (Ma et al , ). Thus, miR‐34a/Sirt1‐mediated NF‐κB signalling is an important pathway of controlling inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of dioscin against cisplatin‐induced nephrotoxicity via the microRNA‐34a/sirtuin 1 signalling pathway

Zhang

Tao

Yin

et al. 2017

British J Pharmacology

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effects of dioscin against cisplatin‐induced nephrotoxicity via the microRNA‐34a/sirtuin 1 signalling pathway

Zhang

Tao

Yin

et al. 2017

British J Pharmacology

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“…In response to cisplatin, several signaling pathways, which can be activated by lipid peroxidation and oxidative stress, modulate the cell survival or apoptosis [18, 19]. The mitogen-activated protein kinase ( MAPK ) pathways regulate differentiation, proliferation, apoptosis and are activated by chemical and physical stresses [20]. The three major MAPK pathways terminate in ERK , p38 , and JNK/SAPK enzymes.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats

et al. 2017

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BackgroundCisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats.MethodsForty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group intraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin group orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys were harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis factors alpha (TNF-α), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-α).ResultsThe cisplatin single dose administration to rats induced nephrotoxicity associated with a significant increase in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in kidney tissues by 230 ± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a significant increase in the expression levels of the IL-1α (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%), JNK (680%) and TNF-α (300%) genes compared to control group. Additionally, histopathological examination showed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute tubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in gene expression and structural and functional changes in the kidney. Additionally, histopathological examination of kidney tissues confirmed gene expression data.ConclusionThe present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent CP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK signaling pathways, and repairing the histopathological changes against cisplatin administration.

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“…However, some studies (both in vitro and in vivo ) have demonstrated that triterpene saponins show a protective effect against cisplatin‐induced cell damage. Saikosaponin D (SSD), isolated from the root of Bupleurum falcatum (Apiaceae), reduces cisplatin‐induced nephrotoxicity by repressing ROS‐mediated activation of MAPK, p38, and NF‐κB signaling pathways in the human kidney proximal tubule HK‐2 cell line (Ma et al, ). Similarly, two saponins (gypsogenin 3‐ O ‐β‐ d ‐galactopyranosyl(1→2)‐(α‐ l ‐rhamnopyranosyl(1→3))‐β‐ d ‐glucuronopyranoside and quillaic acid 3‐ O ‐β‐ d ‐galactopyranosyl(1→2)‐(α‐ l ‐rhamnopyranosyl(1→3))‐β‐ d ‐glucuronopyranoside) obtained from Momordica cochinchinensis Spreg.…”

Section: Triterpene Saponins and Cisplatinmentioning

confidence: 99%

Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug—Minireview of in vitro studies

Koczurkiewicz

Klaś

Grabowska

et al. 2019

Phytotherapy Research

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Triterpene saponins (saponosides) are found in higher plants and display a wide range of biological and pharmacological activities. The antitumor effects of saponins have been proved by their cytotoxic, cytostatic, proapoptotic, and anti‐invasive effects in many cellular models. Saponins hold great potential for being developed into chemopreventive and chemotherapeutic drugs. A promising way of reducing the adverse effects of chemotherapy without attenuating its efficiency is provided by the combined application of chemotherapeutic agents and saponosides in subtoxic concentrations. Until recently, saponosides were primarily used as adjuvants that enhance the effect of vaccines. In cancer therapy, saponins are applied in combination with immunotoxins because they increase the selectivity of given immunotoxins against cancer cells and therefore inure normal cells to the cytotoxic effects of immunotoxins. Significantly, certain saponins have been identified that drastically enhance the efficacy of many chemotherapeutic agents, including cisplatin, paclitaxel, doxorubicin, docetaxel, mitoxantrone, and cyclophosphamide. Moreover, saponins used in combination therapy enhance the sensitivity of chemoresistant tumor cells to clinically used chemotherapeutic agents. This review sheds light on the molecular mechanisms underlying cancer co–treatment with saponins and chemotherapy, with a particular focus on modulation of the cell signaling pathways associated with the promotion and progression of cancer cell proliferation, apoptosis, and metastasis.

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Saikosaponin-D reduces cisplatin-induced nephrotoxicity by repressing ROS-mediated activation of MAPK and NF-κB signalling pathways

Cited by 98 publications

References 42 publications

Protective effects of dioscin against cisplatin‐induced nephrotoxicity via the microRNA‐34a/sirtuin 1 signalling pathway

Protective effects of dioscin against cisplatin‐induced nephrotoxicity via the microRNA‐34a/sirtuin 1 signalling pathway

Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats

Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug—Minireview of in vitro studies

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