title: Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury.
abstract: The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30mg/kg for two successive days, 48h after intraperitoneal injection of CP (13mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery of kidney tissue form CP injury was accompanied by increased proliferating nuclear cell antigen (PCNA) expression. The results of this study suggest that CA attenuates CP-induced kidney injury through suppression of oxidative stress, inflammation, apoptosis and autophagy, with the improvement in kidney regeneration.
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: robert.domitrovic@medri.uniri.hr.
authors.forename: Robert
authors.initials: R
authors.lastname: Domitrović
authors.affiliation: Department of Anatomy, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Olga
authors.initials: O
authors.lastname: Cvijanović
authors.affiliation: Department of Epidemiology, Institute of Public Health, Primorje-Gorski Kotar County, Rijeka, Croatia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Šušnić
authors.affiliation: Department of Clinical Laboratory Diagnostics, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Katalinić
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D002726:Chlorogenic Acid / Q000494:pharmacology*; D002945:Cisplatin; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000097:blood; D000075102:Organic Cation Transporter 2; D018384:Oxidative Stress / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D053148:Caspase 3; D002726:Chlorogenic Acid; D002945:Cisplatin; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D019392:Cytochrome P-450 CYP2E1; D051547:Heme Oxygenase-1; D018836:Inflammation Mediators; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D018809:Proliferating Cell Nuclear Antigen; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C494827:Bax protein, mouse; C530105:Ccnd1 protein, mouse; C480860:Map1lc3b protein, mouse; C491012:Slc22a2 protein, mouse; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; C505409:Casp3 protein, mouse; C027576:4-hydroxy-2-nonenal; C421109:multidrug resistance-associated protein 1
keywords: Apoptosis; Autophagy; Chlorogenic acid; Cisplatin nephrotoxicity; Inflammatory response; Oxidative stress