title: Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.
abstract: The aim of this study was to investigate the therapeutic activity of isoquinoline alkaloid berberine against cisplatin (CP)-induced nephrotoxicity in mice. Berberine was administered at daily doses of 1, 2 and 3 mg/kg by gavage for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Mice were sacrificed 24 h after the last dose of berberine. Histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP were significantly ameliorated by berberine in a dose-dependent manner. Additionally, oxidative/nitrosative stress, evidenced by the increase in renal 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced. The expression of nuclear factor-kappaB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was markedly suppressed by berberine, indicating the inhibition of inflammatory response. Treatment of CP-intoxicated animals with berberine also significantly reduced the expression of p53, active caspase-3 as well as autophagy marker light chain 3B (LC3B) in the kidneys. The results of the current study showed the nephroprotective activity of berberine against CP-induced renal injury, which could be attributed to the inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia. Electronic address: robert.domitrovic@medri.uniri.hr.
authors.forename: Robert
authors.initials: R
authors.lastname: Domitrović
authors.forename: Olga
authors.initials: O
authors.lastname: Cvijanović
authors.forename: Ester
authors.initials: E
authors.lastname: Pernjak-Pugel
authors.forename: Marko
authors.initials: M
authors.lastname: Skoda
authors.forename: Lorena
authors.initials: L
authors.lastname: Mikelić
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Crnčević-Orlić
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009393:Nephritis / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; D020011:Protective Agents; D001599:Berberine; C002744:3-nitrotyrosine; D014443:Tyrosine; D003404:Creatinine; D019392:Cytochrome P-450 CYP2E1; C027576:4-hydroxy-2-nonenal; D002945:Cisplatin
keywords: 3-NT; 3-nitrotyrosine; 4-HNE; 4-hydroxynonenal; Apoptosis; Autophagy; BUN; Berberine; COX-2; CP; CYP2E1; Cisplatin nephrotoxicity; DMSO; FITC; HE; HO-1; IL; Inflammatory response; LC3; NF-κB; NO(); Oxidative stress; PAS; PVDF; RIPA; TNF-α; TUNEL; blood urea nitrogen; cis-diamineplatinum(II) dichloride; cyclooxygenase-2; cytochrome P450 2E1; dimethyl sulfoxide; fluorescein isothiocyanate; hematoxylin and eosin; heme oxygenase-1; iNOS; inducible nitric oxide synthase; interleukin; light chain 3B; nitric oxide; nuclear factor-kappaB; periodic acid-Schiff; polyvinylidene difluoride; radioimmunoprecipitation assay; terminal deoxynucleotidyl transferase dUTP nick end labeling; tumor necrosis factor-alpha