Dataset Information

Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1?.

ABSTRACT: We investigated the role of HIF-1? in the mitigation of cisplatin-induced nephrotoxicity by Panax notoginseng saponins (PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-?-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1? inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular damage in cisplatin-treated rats and which were exacerbated by 2ME2. Renal tissues from PNS-treated rats showed increased HIF-1? mRNA and nuclear localized HIF-1? protein. Moreover, PNS treatment increased BNIP3 mRNA as well as LC3-II, BNIP3 and Beclin-1 proteins and the LC3-II/LC3-I ratio in rat renal tissues. This suggested that PNS treatment enhanced HIF-1?, which in turn increased autophagy. This was confirmed in transmission electron micrographs of renal tissues that showed autophagosomes in PNS-treated renal tissues. These findings demonstrate that PNS mitigates cisplatin-induced nephrotoxicity by enhancing mitophagy via a HIF-1?/BNIP3/Beclin-1 signaling pathway.

SUBMITTER: Liang X

PROVIDER: S-EPMC5732705 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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<i>Panax notoginseng saponins</i> mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α.

Liang Xueyan X Yang Yufang Y Huang Zhenguang Z Zhou Jinling J Li Yue'e Y Zhong Xiaobin X

Oncotarget 20170803 61

We investigated the role of HIF-1α in the mitigation of cisplatin-induced nephrotoxicity by <i>Panax notoginseng saponins</i> (PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular dama ...[more]

PMID: 29262539

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Project description:Statins cannot be used for some active liver diseases, which limits its application to some extent. The combined use of statins with other drugs may be one of the ways to solve this dilemma.This research aims to evaluate the effects of atorvastatin combined with Panax notoginseng saponins (PNS) on rats with atherosclerosis (AS) complicated with hepatic injury.Seventy-two male Wistar rats were randomly categorized into control group (without any intervention, Group A) and AS model groups, which were divided into hepatic injury (Groups B-E) and nonhepatic injury (Groups F-I) groups. Hepatic and nonhepatic injury groups were intragastrically treated with 5.5 mg/kg·d atorvastatin (Group B, F), 200 mg/kg·d PNS (Group C, G), 5.5 mg/kg·d atorvastatin + 200 mg/kg·d PNS (Group D, H), and normal saline (Group E, I). After 8 weeks, total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol, low density lipoprotein-cholesterol (LDL-C), and serum calcium were analyzed to evaluate the hypolipidemic effect. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and r-glutamyltransferase levels were measured to assess liver function. The thoracic aortas were used for hematoxylin-eosin staining.In both hepatic injury and nonhepatic injury groups, TC, TG and LDL-C levels significantly decreased in Groups B, D, F, and H. ALT and AST levels significantly increased in Group B, but significantly decreased in Groups C and D. The aortic intima thickness was significantly lower in Groups B, D, F, and H than that in the normal saline group.The combination of atorvastatin and PNS treatment showed a significant hypolipidemic effect and hepatic enzyme stability function.The single use of Panax notoginseng saponins (PNS) in the rat model for atherosclerosis significantly reduced Ca2+ content in serum, whereas the effect of lowing total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) is not apparent, especially as compared with atorvastatin treatmentPNS combined with atorvastatin treatment of the rat model for atherosclerosis displayed a noticeable, synergistic effect that allowed for better reduction of TC, TG, LDL-C and Ca2+ in the serum than that with the single use of PNS or atorvastatinIn the rat liver injury combined with atherosclerosis model, the single use of PNS significantly improved liver function, whereas atorvastatin alone only aggravated liver injury in the rat model. The effect of PNS combined with atorvastatin on liver function was significantly better than that of atorvastatin aloneThe combined use of PNS and atorvastatin showed good stability of liver function on the liver injury combined with atherosclerosis model. Abbreviations used: PNS: Panax notoginseng saponins; AS: Atherosclerosis; TC: Total cholesterol; TG: Triglyceride; HDL-C: High density lipoprotein-cholesterol; LDL-C: Low density lipoprotein-cholesterol; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; T-BIL: Total bilirubin; r-GT: R-glutamyltransferase; HE: Hematoxylin-eosin.

Dataset Information

Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1?.

Publications

<i>Panax notoginseng saponins</i> mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α.

Similar Datasets

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