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Int J Clin Exp Pathol 2011;4(3):255-266

Original Article
Enhancement of reactive oxygen species and induction of apoptosis in
streptozotocin-induced diabetic rats under hyperbaric oxygen exposure

Tokio Matsunami, Yukita Sato, Yuki Hasegawa, Satomi Ariga, Haruka Kashimura, Takuya Sato, Masayoshi Yukawa  

Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa 252-0880,
Japan.

Received January 31, 2011; accepted February 17, 2011; Epub February 20, 2011; published April 1, 2011

Abstract: An important source of reactive oxygen species (ROS) production is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase,
which on activation induces superoxide production via oxidation in the mitochondria, inflammation and stress; such ROS are implicated in the
pathogenesis of diabetic complications, including neuropathy. Hyperbaric oxygen (HBO) treatments are applied various diseases including
diabetic patients with unhealing foot ulcers, however, and also increases the formation of ROS. In a previous study, we showed that a clinically
recommended HBO treatment significantly enhanced oxidative stress of pancreatic tissue in the diabetic rats. However, no study has been
undertaken with regard to the effects of HBO on the activity and gene expression of the NADPH oxidase complex and on apoptosis in the
pancreas of diabetic animals. The purpose of this study was to investigate the effect of HBO exposure on gene expression of the NADPH
complex, and pancreatic expression of genes related to apoptosis via the mitochondria, using the NADPH oxidase inhibitor apocynin. The
mRNA expression of genes related to NADPH oxidase complex and apoptosis increased significantly (P < 0.05) in the pancreas of diabetic rats
under HBO exposure. Similarly, activities of NADPH oxidase and caspase-3 changed in parallel with mRNA levels. These results suggest that
oxidative stress caused by HBO exposure in diabetic animals induces further ROS production and apoptosis, potentially through the
up-regulation of NADPH oxidase complex. Thus, this study can contribute to development of a better understanding of the molecular
mechanisms of apoptosis via the mitochondria in diabetes, under HBO exposure. (IJCEP1101009).

Keywords: Diabetes mellitus, hyperbaric oxygen, reactive oxygen species, nicotinamide adenine dinucleotide phosphate, apoptosis, apocynin

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Address all correspondence to:
Dr. Yukita Sato
Laboratory of Biomedical Science
Department of Veterinary Medicine, College of Bioresource Sciences
Nihon University, Fujisawa 252-0880, Japan.
Tel and Fax: +81-466-84-3445
E-mail:
sato.yukita@nihon-u.ac.jp