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Low-molecular-weight chitosan scavenges methylglyoxal and N (ε)-(carboxyethyl)lysine, the major factors contributing to the pathogenesis of nephropathy.

Chou CK, Chen SM, Li YC, Huang TC, Lee JA - Springerplus (2015)

Bottom Line: Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction.Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 µg mL(-1).Treatment with lmw-chitosan (500 mg kg(-1) day(-1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 ± 24.34 to 86.15 ± 33.79 µg g(-1) protein (p < 0.05) and CEL levels from 4.60 ± 0.27 to 2.84 ± 0.28 µmol µg(-1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model.

View Article: PubMed Central - PubMed

Affiliation: Chia-Yi Christian Hospital, No. 539 Jhongsiao Rd., Chia-Yi City, 60002 Taiwan ; Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei City, 10002 Taiwan.

ABSTRACT
Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite N (ε)-(carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-molecular-weight chitosan (lmw-chitosan) on MG-induced carbonyl stress in aristolochic acid-induced nephropathy. We used a buffer to investigate whether MG could be scavenged by lmw-chitosan in vitro. In addition, we also used a mouse model of aristolochic acid-induced nephropathy, which exhibits 12-fold greater accumulation of MG in the kidneys than that found in control animals, to examine whether lmw-chitosan could decrease MG levels in vivo. Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 µg mL(-1). Treatment with lmw-chitosan (500 mg kg(-1) day(-1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 ± 24.34 to 86.15 ± 33.79 µg g(-1) protein (p < 0.05) and CEL levels from 4.60 ± 0.27 to 2.84 ± 0.28 µmol µg(-1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model. These data suggest that lmw-chitosan might represent a novel treatment modality for MG-related diseases such as nephropathy.

No MeSH data available.


Related in: MedlinePlus

The protective mechanism of lmw-chitosan. Lmw-chitosan can block MG and CEL accumulation and might improve the damage resulting from protein dysfunction and inflammation. Interactions with carbonyl and oxidative stressors could promote an increase in overall stress. However, the role of lmw-chitosan on carbonyl stress is more vital than that on oxidative stress.
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Fig4: The protective mechanism of lmw-chitosan. Lmw-chitosan can block MG and CEL accumulation and might improve the damage resulting from protein dysfunction and inflammation. Interactions with carbonyl and oxidative stressors could promote an increase in overall stress. However, the role of lmw-chitosan on carbonyl stress is more vital than that on oxidative stress.

Mentions: Figure 4 illustrates a mechanism by which MG accumulation leads to disease and serves as a target for lmw-chitosan binding. Initially, elevated levels of MG and CEL cause significant carbonyl stress in AA-injected mice and in diseases such as nephropathy, and subsequent administration of lmw-chitosan can successfully reverse the increase in MG and CEL levels. However, the lack of response in our animal model suggests that the glutathione level does not represent the primary target of lmw-chitosan; instead, we suggest that the reversal of MG and MG-derived CEL build-up by lmw-chitosan is the key mechanism of this treatment against nephropathy.Figure 4


Low-molecular-weight chitosan scavenges methylglyoxal and N (ε)-(carboxyethyl)lysine, the major factors contributing to the pathogenesis of nephropathy.

Chou CK, Chen SM, Li YC, Huang TC, Lee JA - Springerplus (2015)

The protective mechanism of lmw-chitosan. Lmw-chitosan can block MG and CEL accumulation and might improve the damage resulting from protein dysfunction and inflammation. Interactions with carbonyl and oxidative stressors could promote an increase in overall stress. However, the role of lmw-chitosan on carbonyl stress is more vital than that on oxidative stress.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489968&req=5

Fig4: The protective mechanism of lmw-chitosan. Lmw-chitosan can block MG and CEL accumulation and might improve the damage resulting from protein dysfunction and inflammation. Interactions with carbonyl and oxidative stressors could promote an increase in overall stress. However, the role of lmw-chitosan on carbonyl stress is more vital than that on oxidative stress.
Mentions: Figure 4 illustrates a mechanism by which MG accumulation leads to disease and serves as a target for lmw-chitosan binding. Initially, elevated levels of MG and CEL cause significant carbonyl stress in AA-injected mice and in diseases such as nephropathy, and subsequent administration of lmw-chitosan can successfully reverse the increase in MG and CEL levels. However, the lack of response in our animal model suggests that the glutathione level does not represent the primary target of lmw-chitosan; instead, we suggest that the reversal of MG and MG-derived CEL build-up by lmw-chitosan is the key mechanism of this treatment against nephropathy.Figure 4

Bottom Line: Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction.Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 µg mL(-1).Treatment with lmw-chitosan (500 mg kg(-1) day(-1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 ± 24.34 to 86.15 ± 33.79 µg g(-1) protein (p < 0.05) and CEL levels from 4.60 ± 0.27 to 2.84 ± 0.28 µmol µg(-1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model.

View Article: PubMed Central - PubMed

Affiliation: Chia-Yi Christian Hospital, No. 539 Jhongsiao Rd., Chia-Yi City, 60002 Taiwan ; Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei City, 10002 Taiwan.

ABSTRACT
Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite N (ε)-(carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-molecular-weight chitosan (lmw-chitosan) on MG-induced carbonyl stress in aristolochic acid-induced nephropathy. We used a buffer to investigate whether MG could be scavenged by lmw-chitosan in vitro. In addition, we also used a mouse model of aristolochic acid-induced nephropathy, which exhibits 12-fold greater accumulation of MG in the kidneys than that found in control animals, to examine whether lmw-chitosan could decrease MG levels in vivo. Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 µg mL(-1). Treatment with lmw-chitosan (500 mg kg(-1) day(-1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 ± 24.34 to 86.15 ± 33.79 µg g(-1) protein (p < 0.05) and CEL levels from 4.60 ± 0.27 to 2.84 ± 0.28 µmol µg(-1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model. These data suggest that lmw-chitosan might represent a novel treatment modality for MG-related diseases such as nephropathy.

No MeSH data available.


Related in: MedlinePlus