β-Lapachone enhances Mre11-Rad50-Nbs1 complex expression in cisplatin-induced nephrotoxicity

Background recent studies suggest a potential involvement of the mre11-rad50-nbs1 (mrn) complex,a dna double-strand breaks (dsbs) sensor,in the development of nephrotoxicity following cisplatin administration. β-lapachone is a topoisomerase i inhibitor known to reduce cisplatin-induced nephrotoxicity. in this study,by assessing mrn complex expression,we explored whether β-lapachone was involved in dna damage response in the context of cisplatin-induced nephrotoxicity. methods male balb/c mice were randomly allocated to 4 groups: control,β-lapachone alone,cisplatin alone,and β-lapachone + cisplatin. β-lapachone was administered with the diet (0.066%) for 2 weeks prior to cisplatin injection (18 mg/kg). all mice were sacrificed 3 days after cisplatin treatment. results in the cisplatin-alone group,renal function was disrupted and mrn complex expression increased. as expected,β-lapachone co-treatment attenuated cisplatin-induced pathologic alterations. notably,although β-lapachone markedly decreased cisplatin-induced renal cell apoptosis and dsbs formation,the β-lapachone + cisplatin group showed the highest mrn complex expression. moreover,β-lapachone treatment increased the basal expression level of the mrn complex,which was accompanied by enhanced basal expression of sirtuin1,which is known to regulate nbs1 acetylation. conclusion although,it remains unclear how β-lapachone induces mrn complex expression,our findings suggest that β-lapachone might affect mrn complex expression and participate in dna damage recovery in cisplatin-induced nephrotoxicity. © 2015 institute of pharmacology,polish academy of sciences. all rights reserved.