Abstract
We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Albuminuria / etiology
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Albuminuria / metabolism
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Albuminuria / prevention & control
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Animals
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Antioxidants / administration & dosage
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Antioxidants / isolation & purification
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Antioxidants / pharmacology*
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Bilirubin / pharmacology
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Biliverdine / pharmacology
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Cells, Cultured
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / metabolism
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Diabetic Nephropathies / etiology
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Diabetic Nephropathies / genetics
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Diabetic Nephropathies / metabolism
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Diabetic Nephropathies / pathology
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Diabetic Nephropathies / physiopathology
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Diabetic Nephropathies / prevention & control*
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Disease Models, Animal
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Fibronectins / metabolism
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Gene Expression Regulation
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Humans
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Kidney / drug effects*
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Kidney / metabolism
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Kidney / pathology
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Kidney / physiopathology
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Male
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Mice
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Mice, Inbred C57BL
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NADPH Oxidases / metabolism
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Oxidative Stress / drug effects*
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Phycobilins / administration & dosage
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Phycobilins / isolation & purification
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Phycobilins / pharmacology*
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Phycocyanin / administration & dosage
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Phycocyanin / isolation & purification
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Phycocyanin / pharmacology*
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Spirulina / chemistry*
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Superoxides / metabolism
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Time Factors
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Transforming Growth Factor beta / metabolism
Substances
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Antioxidants
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Fibronectins
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Phycobilins
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Transforming Growth Factor beta
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Phycocyanin
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Superoxides
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phycocyanobilin
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NADPH Oxidases
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Biliverdine
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Bilirubin