Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivo.
Exposure of cells to gamma-rays induces the production of reactive oxygen species (ROS) that play a main role in ionizing radiation damage. We have investigated the radioprotective effect of phloroglucinol (1,3,5-trihydroxybenzene), phlorotannin compound isolated from Ecklonia cava, against gamma-ray radiation-induced oxidative damage in vitro and in vivo. Phloroglucinol significantly decreased the level of radiation-induced intracellular ROS and damage to cellular components such as the lipid, DNA and protein. Phloroglucinol enhanced cell viability that decreased after exposure to gamma-rays and reduced radiation-induced apoptosis via inhibition of mitochondria mediated caspases pathway. Phloroglucinol reduced radiation-induced loss of the mitochondrial membrane action potential, reduced the levels of the active forms of caspase 9 and 3 and elevated the expression of bcl-2. Furthermore, the anti-apoptotic effect of phloroglucinol was exerted via inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1), c-Jun NH(2)-terminal kinase (JNK) and activator protein-1 (AP-1) cascades induced by radiation exposure. Phloroglucinol restored the level of reduced glutathione (GSH) and protein expression of a catalytically active subunit of glutamate-cysteine ligase (GCL), which is a rate-limiting enzyme in GSH biosynthesis. In in vivo study, phloroglucinol administration in mice provided substantial protection against death and oxidative damage following whole-body irradiation. We examined survival with exposure to various radiation doses using the intestinal crypt assay and determined a dose reduction factor (DRF) of 1.24. Based on our findings, phloroglucinol may be possibly useful as a radioprotective compound.
Kang
Kyoung Ah
KA
Jeju National University School of Medicine and Applied Radiological Science Research Institute, Jeju-si 690-756, Republic of Korea.
Zhang
Rui
R
Chae
Sungwook
S
Lee
Su Jae
SJ
Kim
Jihoon
J
Kim
Jeongtae
J
Jeong
Jinwoo
J
Lee
Juyeon
J
Shin
Taekyun
T
Lee
Nam Ho
NH
Hyun
Jin Won
JW
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage; D005260:Female; D005720:Gamma Rays; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D010696:Phloroglucinol / Q000737:chemistry / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D010696:Phloroglucinol; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020169:Caspases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione