title: Riceberry bran extract prevents renal dysfunction and impaired renal organic anion transporter 3 (Oat3) function by modulating the PKC/Nrf2 pathway in gentamicin-induced nephrotoxicity in rats.
abstract: OBJECTIVE
  This study investigated the protective effects of Riceberry bran extract (RBBE) on renal function, and the function and expression of renal organic anion transporter 3 (Oat3) in gentamicin-induced nephrotoxicity in rats and explored the mechanisms for its protective effects.
  
  
  METHODS
  Male Sprague Dawley rats (n= 42) were divided into six groups to receive normal saline, gentamicin (100mg/kg), co-treatment of gentamicin and RBBE (at dose of 250, 500 and 1000mg/kg), and RBBE (at dose of 1000mg/kg) only, for consecutive fifteen days. Renal function, oxidative and antioxidative markers, the function and expression of Oat3 and histological changes in the kidney were evaluated.
  
  
  RESULTS
  Elevation of BUN, serum creatinine levels and reduction in urine creatinine and creatinine clearance indicated decreased renal function in the gentamicin-treated rats. The decrease of [3H]ES uptake in the renal cortical slices of these rats, reflecting the attenuation of Oat3 transport function that was accompanied by decreased expression of Oat3. Moreover, increased MDA level and reduced superoxide dismutase (SOD) and glutathione (GSH) activities were found in gentamicin-treated rats compared to the control group. These changes were associated with the upregulated PKCα, Nrf-2, Keap 1, NQO-1 and HO-1 expressions in kidneys. RBBE treatment improved the renal function and Oat3 transport function and expression in gentamicin-treated rats. The oxidative status was also restored by RBBE treatment.
  
  
  CONCLUSIONS
  RBBE protects kidney injury by its antioxidant effect, subsequently leading to modulation of the PKC/Nrf2 antioxidant defense pathway.
authors.affiliation: Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Phatchawan
authors.initials: P
authors.lastname: Arjinajarn
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Pongchaidecha
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nuttawud
authors.initials: N
authors.lastname: Chueakula
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Krit
authors.initials: K
authors.lastname: Jaikumkao
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Varanuj
authors.initials: V
authors.lastname: Chatsudthipong
authors.affiliation: Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sugunya
authors.initials: S
authors.lastname: Mahatheeranont
authors.affiliation: Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Orranuch
authors.initials: O
authors.lastname: Norkaew
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Electronic address: onanusorn@yahoo.com.
authors.forename: Anusorn
authors.initials: A
authors.lastname: Lungkaphin
mesh_terms: D000818:Animals; D008297:Male; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D005839:Gentamicins / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism; D007677:Kidney Function Tests; D027361:Organic Anion Transporters / Q000378:metabolism; D012275:Oryza; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011493:Protein Kinase C / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012639:Seeds; D013482:Superoxide Dismutase / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005839:Gentamicins; D005978:Glutathione; D027361:Organic Anion Transporters; D010936:Plant Extracts; D020011:Protective Agents; D011493:Protein Kinase C; D013482:Superoxide Dismutase; D051267:NF-E2-Related Factor 2
keywords: Gentamicin; Nephrotoxicity; Organic anion transporter 3; Oxidative stress; Riceberry bran extract