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An inhibitor of advanced glycation end product formation reduces N epsilon-(carboxymethyl)lysine accumulation in glomeruli of diabetic rats.
Am J Kidney Dis 2003; 41(3 Suppl 1):S68-71AJ

Abstract

BACKGROUND

An inhibitor of advanced glycation, OPB-9195, retards the progression of nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus. The aim of this study is to evaluate histologically the role of N(epsilon)-(carboxymethyl)lysine (CML) in the development of diabetic nephropathy and investigate whether inhibition of CML accumulation by OPB-9195 is associated directly with the prevention of glomerular lesions in OLETF rats.

METHODS

Kidneys of OLETF and Long-Evans Tokushima Otsuka rats were obtained at ages 7, 20, 50, and 68 weeks after collecting their blood and urine samples. OPB-9195 had been administered to the rats from age 24 weeks to the end of the experiments. CML in kidneys was detected by using a monoclonal antibody against CML according to an indirect immunofluorescence technique. CML-positive glomerular area was measured using NIH Image software (Research Services Branch of NIMH, Bethesda, MD). Hyalinized and/or sclerotic areas in glomeruli and mesangial and glomerular volume were measured using a point-counting technique.

RESULTS

CML-positive area in glomeruli correlated closely not only with urinary albumin excretion (r = 0.912; P = 0.001), but also with volumes of mesangium and hyalinized and/or sclerotic lesions (r = 0.859; P = 0.0019 and r = 0.833; P = 0.0027, respectively). Treatment with OPB-9195 reduced CML-positive area and prevented the increase in mesangial volume, with no significant change in glomerular volume at age 68 weeks. The volume of hyalinized and/or sclerotic lesions also decreased by treatment with OPB-9195 in three of four rats at age 68 weeks.

CONCLUSION

CML is a major advanced glycation end product contributing to the development of diabetic nephropathy, and inhibition of its accumulation by OPB-9195 results in amelioration of glomerular lesions in OLETF rats.

Authors+Show Affiliations

Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12612956

Citation

Nakamura, Sakurako, et al. "An Inhibitor of Advanced Glycation End Product Formation Reduces N Epsilon-(carboxymethyl)lysine Accumulation in Glomeruli of Diabetic Rats." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 41, no. 3 Suppl 1, 2003, pp. S68-71.
Nakamura S, Tachikawa T, Tobita K, et al. An inhibitor of advanced glycation end product formation reduces N epsilon-(carboxymethyl)lysine accumulation in glomeruli of diabetic rats. Am J Kidney Dis. 2003;41(3 Suppl 1):S68-71.
Nakamura, S., Tachikawa, T., Tobita, K., Aoyama, I., Takayama, F., Enomoto, A., & Niwa, T. (2003). An inhibitor of advanced glycation end product formation reduces N epsilon-(carboxymethyl)lysine accumulation in glomeruli of diabetic rats. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 41(3 Suppl 1), pp. S68-71.
Nakamura S, et al. An Inhibitor of Advanced Glycation End Product Formation Reduces N Epsilon-(carboxymethyl)lysine Accumulation in Glomeruli of Diabetic Rats. Am J Kidney Dis. 2003;41(3 Suppl 1):S68-71. PubMed PMID: 12612956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An inhibitor of advanced glycation end product formation reduces N epsilon-(carboxymethyl)lysine accumulation in glomeruli of diabetic rats. AU - Nakamura,Sakurako, AU - Tachikawa,Tetsuya, AU - Tobita,Kazuki, AU - Aoyama,Isao, AU - Takayama,Fumio, AU - Enomoto,Atsushi, AU - Niwa,Toshimitsu, PY - 2003/3/4/pubmed PY - 2003/3/15/medline PY - 2003/3/4/entrez SP - S68 EP - 71 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 41 IS - 3 Suppl 1 N2 - BACKGROUND: An inhibitor of advanced glycation, OPB-9195, retards the progression of nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus. The aim of this study is to evaluate histologically the role of N(epsilon)-(carboxymethyl)lysine (CML) in the development of diabetic nephropathy and investigate whether inhibition of CML accumulation by OPB-9195 is associated directly with the prevention of glomerular lesions in OLETF rats. METHODS: Kidneys of OLETF and Long-Evans Tokushima Otsuka rats were obtained at ages 7, 20, 50, and 68 weeks after collecting their blood and urine samples. OPB-9195 had been administered to the rats from age 24 weeks to the end of the experiments. CML in kidneys was detected by using a monoclonal antibody against CML according to an indirect immunofluorescence technique. CML-positive glomerular area was measured using NIH Image software (Research Services Branch of NIMH, Bethesda, MD). Hyalinized and/or sclerotic areas in glomeruli and mesangial and glomerular volume were measured using a point-counting technique. RESULTS: CML-positive area in glomeruli correlated closely not only with urinary albumin excretion (r = 0.912; P = 0.001), but also with volumes of mesangium and hyalinized and/or sclerotic lesions (r = 0.859; P = 0.0019 and r = 0.833; P = 0.0027, respectively). Treatment with OPB-9195 reduced CML-positive area and prevented the increase in mesangial volume, with no significant change in glomerular volume at age 68 weeks. The volume of hyalinized and/or sclerotic lesions also decreased by treatment with OPB-9195 in three of four rats at age 68 weeks. CONCLUSION: CML is a major advanced glycation end product contributing to the development of diabetic nephropathy, and inhibition of its accumulation by OPB-9195 results in amelioration of glomerular lesions in OLETF rats. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/12612956/An_inhibitor_of_advanced_glycation_end_product_formation_reduces_N_epsilon__carboxymethyl_lysine_accumulation_in_glomeruli_of_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272638603500683 DB - PRIME DP - Unbound Medicine ER -