In vitro and in vivo phototoxicity on gastric mucosa induced by methylene blue
Hui Yeong Oh1, Hyun Ho Choi1, Eui Jin Kim1, Ji Hye Choi1, Sung Sook Choi2, Hae Kyung Lee3, Hyung-Keun Kim1, Sang Woo Kim1, Won Sang H. Park4, Hiun Suk Chae1
1 Department of Internal Medicine, Uijongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
2 College of Pharmacy, Sahmyook University, Seoul, Republic of Korea
3 Department of Laboratory Medicine, Uijongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
4 Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Prof. Hiun Suk Chae
Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea
Republic of Korea
Source of Support: None, Conflict of Interest: None
Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity.
Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay.
Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10.
Conclusions: Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.