title: Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury.
abstract: In previous studies, we have demonstrated the biological activity of thymoquinone (TQ), an active compound extracted from the Nigella sativa plant, against cisplatin-induced neurotoxicity. Recenty, it was observed that there is an inherent lack in regulation of renal organic anion and cation transporters in cisplatin-induced nephrotoxicity. Here, we report, for the first time, the effect of TQ on alterations in the renal expression of organic anion transporters (OATs) and organic cation transporters (OCTs), as well as multidrug resistance-associated proteins (MRPs) in rats treated with cisplatin. Twenty-eight 8-week-old male Wistar rats were divided into four groups of control, TQ treated (10 mg/kg b.w. in drinking water for 5 days), cisplatin (7 mg/kg b.w., i.p.) and TQ and cisplatin combination treatment. Cisplatin-induced malondialdehyde (MDA) and 8-isoprostane increase was found to be markedly reduced in rats treated with TQ. In cisplatin only treated rats, the induced renal injury increased protein levels of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and OCT2 was reduced. In combination TQ- and cisplatin-treated rats, expression of MRP2 and MRP4 proteins was decreased in the kidneys. Conversely, TQ treatment increased levels of OCT1, OCT2, OAT1 and OAT3 and decreased levels of 8-isoprostane and MDA levels in cisplatin-treated rats. In conclusion, the present study shows that the TQ synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.
authors.affiliation: Department of Nephrology, Faculty of Medicine, Firat University, Elazig, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Ulu
authors.forename: Ayhan
authors.initials: A
authors.lastname: Dogukan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Hasan
authors.initials: H
authors.lastname: Gencoglu
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ulas
authors.forename: Necip
authors.initials: N
authors.lastname: Ilhan
authors.forename: Irfana
authors.initials: I
authors.lastname: Muqbil
authors.forename: Ramzi M
authors.initials: RM
authors.lastname: Mohammad
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D016227:Benzoquinones / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D027361:Organic Anion Transporters / Q000502:physiology*; D027701:Organic Cation Transport Proteins / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D008315:Malondialdehyde; C003466:thymoquinone; D002945:Cisplatin