Modulation of renal superoxide dismutase by telmisartan therapy in C57BL/6-Ins2Akita diabetic mice

Autor: Yuichiro Yamada, Hiroki Fujita, Takamune Takahashi, Mihoko Hosoba, Takuma Narita, Tsukasa Morii, Takuya Sakamoto, Koga Komatsu, Hiromi Fujishima, Keiko Takahashi
Rok vydání: 2011
Předmět:
Blood Glucose
Male
Physiology
telmisartan
Kidney
medicine.disease_cause
Benzoates
angiotensin II type 1 receptor blocker
Mice
chemistry.chemical_compound
Superoxides
Diabetic Nephropathies
Enzyme Inhibitors
Oxidase test
biology
Chemistry
Superoxide
Immunohistochemistry
Original Article
Cardiology and Cardiovascular Medicine
medicine.drug
medicine.medical_specialty
NF-E2-Related Factor 2
Blotting
Western
Dinoprostone
Superoxide dismutase
Internal medicine
Diabetes Mellitus
Internal Medicine
medicine
Animals
Antihypertensive Agents
Superoxide Dismutase
diabetic nephropathy
NAD(P)H oxidase
Acetophenones
NADPH Oxidases
Angiotensin II
Mice
Inbred C57BL
Endocrinology
Hyperglycemia
Apocynin
biology.protein
Benzimidazoles
Amlodipine
NAD+ kinase
Telmisartan
Angiotensin II Type 1 Receptor Blockers
Blood Chemical Analysis
Oxidative stress
Zdroj: Hypertension Research
ISSN: 1348-4214
0916-9636
DOI: 10.1038/hr.2011.176
Popis: Renal superoxide excess, which is induced by an imbalance of the superoxide-producing enzyme NAD(P)H oxidase and the superoxide-scavenging enzyme superoxide dismutase (SOD) under hyperglycemia, increases oxidative stress and contributes to the development of diabetic nephropathy. In this study, we treated non-obese and hypoinsulinemic C57BL/6-Ins2(Akita) (C57BL/6-Akita) diabetic mice with telmisartan (5 mg kg(-1) per day), an angiotensin II type 1 receptor blocker, or amlodipine (5 mg kg(-1) per day), a calcium channel blocker, for 4 weeks and compared the effects of these two anti-hypertensive drugs on renal NAD(P)H oxidase, SOD and transcription factor Nrf2 (NF-E2-related factor 2), which is known to upregulate several antioxidant enzymes including SOD. Vehicle-treated C57BL/6-Akita mice exhibited higher renal NAD(P)H oxidase and lower renal SOD activity with increased levels of renal superoxide than the C57BL/6-wild-type non-diabetic mice. Interestingly, telmisartan treatment not only reduced NAD(P)H oxidase activity but also enhanced SOD activity in C57BL/6-Akita mouse kidneys, leading to a reduction of renal superoxide levels. Furthermore, telmisartan-treated C57BL/6-Akita mice increased the renal protein expression of SOD and Nrf2. In parallel with the reduction of renal superoxide levels, a reduction of urinary albumin levels and a normalization of elevated glomerular filtration rate were observed in telmisartan-treated C57BL/6-Akita mice. In contrast, treatment with amlodipine failed to modulate renal NAD(P)H oxidase, SOD and Nrf2. Finally, treatment of C57BL/6-Akita mice with apocynin, an NAD(P)H oxidase inhibitor, also increased the renal protein expression of SOD and Nrf2. Collectively, our data suggest that NAD(P)H oxidase negatively regulates renal SOD, possibly by downregulation of Nrf2, and that telmisartan could upregulate renal SOD by the suppression of NAD(P)H oxidase and subsequent upregulation of Nrf2, leading to the amelioration of renal oxidative stress and diabetic renal changes.
Databáze: OpenAIRE
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