title: Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in rat models.
abstract: This study investigates the mechanism of the protective effect of Panax notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a single dose of cisplatin and a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the concentrations of urinary N-acetyl-β-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue was examined using H&E-staining, and the mitochondria of renal tubular epithelial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein-1 light chain (LC)3, autophagy-related gene (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western blotting. The expression of HIF-1 was detected by immunohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and Scr, the attenuation of renal histopathological changes and the mitochondrial damages of renal cells, and the increase of mitochondria autophagosome in renal tubular epithelial cells. Additionally, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5 and Beclin-1 in rat renal tissue. In conclusion, the protective effect of PNS on cisplatin-induced nephrotoxicity was mainly due to its ability to enhancing the mitochondrial autophagy of renal tissue via the HIF-1α/BNIP3 pathway, and here is the first demonstration about it.
authors.affiliation: a Department of Pharmacy , the First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Department of Pharmacy , the First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Zhenguang
authors.initials: Z
authors.lastname: Huang
authors.affiliation: a Department of Pharmacy , the First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zou
authors.affiliation: a Department of Pharmacy , the First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Department of Pharmacy , the First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: a Department of Pharmacy , the First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000627:therapeutic use*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000648:ultrastructure; D053723:Panax notoginseng / Q000737:chemistry*; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D051793:Hypoxia-Inducible Factor 1; D002945:Cisplatin
keywords: Autophagy; Panax notoginseng saponins; cisplatin-induced nephrotoxicity; mitochondria