title: Ginsenosides protect apical transporters of cultured proximal tubule cells from dysfunctions induced by h(2)o(2).
abstract: Oxidative stress has been implicated as a primary cause of renal failure in certain renal diseases. Indeed, renal proximal tubule is a very sensitive site to oxidative stress and retains functionally fully characterized transporters. It has been reported that ginsenosides have a beneficial effect on diverse diseases including oxidative stress. However, the protective effect of ginsenosides on oxidative stress has not been elucidated in renal proximal tubule cells. Thus, we examined the effect of ginsenosides on oxidative stress-induced alteration of apical transporters and its related mechanism in renal proximal tubule cells. In the present study, hydrogen peroxide (H(2)O(2)) (>10(-5) M) inhibited alpha-methyl-D-glucopyranoside uptake in a dose-dependent manner (p < 0.05). It also inhibited Pi and Na(+) uptake. At a concentration of 20 microg/ml, total ginsenosides significantly reduced H(2)O(2)-induced inhibition of apical transporters. In contrast, protopanaxadiol (PD) and protopanaxatriol (PT) saponins exhibited a less preventive effect than total ginsenosides (p < 0.05). Furthermore, we examined its action mechanism. H(2)O(2) increased lipid peroxide formation, arachidonic acid (AA) release, and Ca(2+) uptake. These effects on H(2)O(2) were significantly prevented by total ginsenosides and PD or PT sanponins. However, total ginsenosides appear to be more protective than PD and PT saponins (p < 0.05). In conclusion, ginsenosides prevented H(2)O(2)-induced inhibition of apical transporters via a decrease in oxidative stress, AA release, and Ca(2+) uptake in primary cultured renal proximal tubule cells.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University, Kwangju, Korea. hjhan@chonnam.ac.kr
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Yoon
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Ji Yeong
authors.initials: JY
authors.lastname: Park
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Oh
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism*; D008757:Methylglucosides / Q000493:pharmacokinetics; D018384:Oxidative Stress / Q000502:physiology; D010758:Phosphorus / Q000493:pharmacokinetics; D011817:Rabbits; D012502:Sapogenins / Q000494:pharmacology; D012964:Sodium / Q000493:pharmacokinetics; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D036145:Ginsenosides; D008054:Lipid Peroxides; D026901:Membrane Transport Proteins; D008757:Methylglucosides; D012502:Sapogenins; D014315:Triterpenes; D016718:Arachidonic Acid; D010758:Phosphorus; C081552:protopanaxatriol; C027020:methylglucoside; D012964:Sodium; D006861:Hydrogen Peroxide; C062916:protopanaxadiol; D002118:Calcium