Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 May 2003 : Case report  

Use of PARP inhibitors to counteract the side effects of cytotoxic drugs

B. Sumegi, P. Deres

Med Sci Monit 2003; 9(1): 65- :: ID: 15204


Many antitumor drugs (doxorubicin (DOX), cisplatin (CisP), and AZT) induce oxidative stress in several tissues, which can contribute to their side effects [1–3]. Oxidative stress can trigger DNA damage and poly(ADP-ribose) polymerase (PARP) activation, which may contribute to an important pathway of cell dysfunction and tissue injury under the conditions associated with oxidative insult [4]. Oxidative injury is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), in the cardiotoxicity of AZT and in the nephrotoxicity caused by cisplatin. Thus, we and others hypothesized that the activation of PARP may contribute to the antitumor drug-induced cardiotoxicity and cisplatin-induced nephrotoxicity. DOX administration in PARP-1+/+ mice depressed left ventricular performance, while the heart function of PARP-1–/– ones and PARP-1+/+ mice treated with PJ34 (1) or HO-3089 (experimental PARP inhibitors) was deteriorated only to a smaller extent. Our data showed that PARP inhibitors activated cardiac Akt and GSK-3b, which may have contributed to their protective effect. Cisplatin-induced kidney dysfunction was prevented by another PARP inhibitor, BGP-15. The cisplatin-caused edema formation was reversed as showed by MRI analysis. High-energy phosphate intermediate levels were reestablished by BGP-15 treatment demonstrated in vivo by localized NMR spectroscopy, which was correlated with the diminished ADP-ribosylation in BGP-15-treated mice [3]. However, the anti-cytostatic effect of cisplatin was not compromised. These data indicate that PARP inhibitors may be applied in combination with cytostatic drugs and their side effects in the heart and kidney can be attenuated without compromising their antitumor efficacy. References: 1.Pacher P, Liaudet L, Bai P et al: Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure. J Pharmacol Exp Ther, 2002 Mar; 300(3): 862-7 2.Szabados E, Fisher MG, Toth K et al: Role of reactive oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced cardiomyopathy in rat. Free Rad Biol & Med, 1999; 26: 309-317 3.Rabloczky G, Jaszlits L, Bárdos G, et al: Chemoprotective Effect Of A Novel PARP Inhibitor. Therapeutic utilities of PARP inhibitors, 2002; 223-228 4.Halmosi R, Berente Z, Osz E et al: Effect of Poly (ADP-Ribose) Polymerase Inhibitors on the Ischemia-Reperfusion Induced Oxidative Cell Damage and Mitochondrial Metabolism in Langendorff Heart Perfusion System. Mol Pharmacol, 2001; 59: 1497-1505

Keywords: PARP, ADP-ribose, cancer, Doxorubicin, akt. Phosphorylation



01 May 2022 : Editorial  

Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937048

Med Sci Monit 2022; 28:e937048


24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

04 May 2022 : Clinical Research  

Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936069  

27 May 2022 : Clinical Research  

Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)

Med Sci Monit 2022; 28:e936547

In Press

25 May 2022 : Review article  

Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation

Med Sci Monit In Press; DOI: 10.12659/MSM.935665  

24 May 2022 : Clinical Research  

Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936580  

24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

23 May 2022 : Clinical Research  

Fully Automatic Knee Joint Segmentation and Quantitative Analysis for Osteoarthritis from Magnetic Resonanc...

Med Sci Monit In Press; DOI: 10.12659/MSM.936733  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750