BGP-15 - A novel poly(ADP-ribose) polymerase inhibitor - Protects against nephrotoxicity of cisplatin without compromising its antitumor activity

Ildiko Racz, Kalman Tory, Ferenc Gallyas, Zoltán Berente, Erzsebet Osz, Laszlo Jaszlits, Sandor Bernath, Balazs Sumegi, Gyorgy Rabloczky, Peter Literati-Nagy

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70 Citations (Scopus)


Nephrotoxicity is one of the major dose limiting side effects of cisplatin chemotherapy. The antitumor and toxic effects are mediated in part by different mechanisms, thus, permitting a selective inhibition of certain side effects. The influence of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) - a poly(ADP-ribose) polymerase (PARP) inhibitor - on the nephrotoxicity and antitumor efficacy of cisplatin has been evaluated in experimental models. BGP-15 either blocked or significantly reduced (60-90% in 100-200mg/kg oral dose) cisplatin induced increase in serum urea and creatinine level in mice and rats and prevented the structural degeneration of the kidney, as well. The nephroprotective effect of BGP-15 treatment was revealed also in living mice by MRI analysis manifesting in the lack of oedema which otherwise developed as a result of cisplatin treatment. The protective effect was accompanied by inhibition of cisplatin-induced poly-ADP-ribosylation and by the restoration of the disturbed energy metabolism. The preservation of ATP level in the kidney was demonstrated in vivo by localized NMR spectroscopy. BGP-15 decreased cisplatin-induced ROS production in rat kidney mitochondria and improved the antioxidant status of the kidney in mice with cisplatin-induced nephropathy. In rat kidney, cisplatin caused a decrease in the level of Bcl-x, a mitochondrial protective protein, and this was normalized by BGP-15 treatment. On the other hand, BGP-15 did not inhibit the antitumor efficacy of cisplatin in cell culture and in transplantable solid tumors of mice. Treatment with BGP-15 increased the mean survival time of cisplatin-treated P-388 leukemia bearing mice from 13 to 19 days. PARP inhibitors have been demonstrated to diminish the consequences of free radical-induced damage, and this is related to the chemoprotective effect of BGP-15, a novel PARP inhibitor. Based on these results, we propose that BGP-15 represents a novel, non-thiol chemoprotective agent.

Original languageEnglish
Pages (from-to)1099-1111
Number of pages13
JournalBiochemical Pharmacology
Issue number6
Publication statusPublished - Mar 15 2002


  • Chemoprotection
  • Cisplatin
  • Nephrotoxicity
  • Poly(ADP-ribose) polymerase
  • Side effect

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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