Alteration of antioxidants during the progression of heart disease in streptozotocin-induced diabetic rats.
Involvement of oxidative stress is implicated in the progression of complication of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotocin to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic posterior wall velocity and rate of LV pressure change, and increase in LV end diastolic pressures also proved cardiac dysfunction. These changes were further developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitochondrial metabolism of reactive oxygen species. The level of glutathione (GSH) decreased concomitant with a decrease in the expression of gamma-glutamylcysteine synthetase (gamma-GCS). The expression of transforming growth factor-beta1 (TGF-beta1), known as a growth factor and a suppressor of GSH synthesis, elevated in DM rat hearts. Immunohistochemical estimation showed an increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of Mn-SOD and elevation of the expression of TGF-beta1 to lead suppression of GSH synthesis and induction of fibrous change for the consequent cardiac dysfunction in DM.
Third Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
K
K
Doi
F
F
Sawada
G
G
Toda
S
S
Yamachika
S
S
Seto
Y
Y
Urata
Y
Y
Ihara
N
N
Sakata
N
N
Taniguchi
T
T
Kondo
K
K
Yano
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism*; D004562:Electrocardiography; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism*; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000975:Antioxidants; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione