Anti-apoptotic effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, against multiple organ damage induced by gamma irradiation in rats

Abstract

Purpose: This study aimed to investigate the effect of 3-aminobenzamide (3-AB) in doses of 5, 10 and 15 mg/kg on the inhibition of Poly (ADP-ribose) polymerase (PARP) when combined with ionizing radiation (IR).

Material and methods: Rats were treated intraperitonealy, one hour prior to irradiation at a dose level of 6 Gray (Gy) and were sacrificed 24 hours after irradiation. Control groups were run concurrently.

Results: IR led to an increase of thiobarbituric acid reactive substance (TBARS), nitrite as well as a decrease in total antioxidant capacity associated increase in myeloperoxidase (MPO) with the expression of cyclooxygenase-2 (COX-2). Moreover, IR caused an increase in serum lactate dehydrogenase (LDH) activity and cytosolyic Ca⁺² associated with an expression of Caspase-3 as well as a decline in complex-I activity and adenosine triphosphate (ATP) level. Pretreatment with 5 and 10 mg/kg of 3AB guarded against the changes in all the measured parameters, conversely the dose of 15 mg/kg showed no effect on the damage induced by irradiation in the selected tissues. Moreover, 3AB has a dose-dependent effect on viability of Vero cells.

Conclusion: The selected low doses of 3AB rather than the higher dose (15 mg/kg) protected against radiation-induced multiple organ damage.

Keywords:

• Ionizing radiation
• multiple organ damage
• apoptosis
• 3-aminobenzamide
• (PARP) inhibition

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval: All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Notes on contributors

Marwa Mohey El-Sheikh, MSc, Assistant Lecturer in Pharmacology and Toxicology, Department of Drug Radiation Research, NCRRT, Atomic Energy Authority, Cairo, Egypt.

Rania Mostafa El-Hazek, PhD, Lecturer in Pharmacology and Toxicology, Department of Drug Radiation Research, NCRRT, Atomic Energy Authority, Cairo, Egypt.

Aiman Saad El-Khatib, PhD, Professor in Pharmacology and Toxicology, Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Mona AbdEl-Latif El-Ghazaly, PhD, Professor in Pharmacology and Toxicology, Department of Drug Radiation Research, NCRRT, Atomic Energy Authority, Cairo, Egypt.