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. 2010 Feb 26;393(1):118-22.
doi: 10.1016/j.bbrc.2010.01.095. Epub 2010 Feb 1.

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type 1) diabetic rats

Ryoji Nagai  1 , Mime Nagai, Satoko Shimasaki, John W Baynes, Yukio Fujiwara
Affiliations

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type 1) diabetic rats

Ryoji Nagai et al. Biochem Biophys Res Commun. .

Abstract

Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end-products (AGEs) such as N(epsilon)-(carboxyethyl)lysine (CEL) and N(epsilon)-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis. We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes.

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Figures

Fig. 1
Fig. 1. Changes in body weight and clinical parameters
Control and diabetic rats were maintained for 27 weeks. Body weight (A) of normal (closed circle), diabetic control (DM) (open triangle), diabetic with insulin therapy (closed circle) and diabetic with citric acid (open circle) was measured continuously, and ketone bodies (B) were measured at the end of the study. Progression of nephropathy was assessed by measurements of 24-h urinary total protein (C) and albumin (D) excretion at 27 weeks. Data are mean±SD. *, P < 0.05; **, P < 0.01 vs diabetic control (DM) group.
Fig. 2
Fig. 2. Cataractogenesis and AGEs accumulation in lens proteins
Rat lenses were removed from eye balls and backscattering of light was determined by putting the lenses on a grid sheet (A), and the progression of cataract was compared in each group (B). The contents of CEL (C) and CML (D) in lenses were analyzed by GC-MS/MS as described in materials and methods. Data are mean±SD. *, P < 0.05; **, P < 0.01 vs diabetic control (DM) group.
Fig. 3
Fig. 3. Formation of CEL from the metabolite of ketone body
Formation of CEL during incubation of HSA with acetol was determined by ELISA (A) in the presence of DTPA (open circle), citric acid (triangle) or absence of interventions (closed circle). CEL content was also measured by HPLC (B) as described in materials and methods.
Fig. 4
Fig. 4
Possible pathway of CEL formation during incubation of protein with acetol
See this image and copyright information in PMC

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