A copper chelating agent suppresses carbonyl stress in diabetic rat lenses.
To clarify whether transition metals are involved in carbonyl stress in diabetic tissues, we observed the effects of a metal chelating agent, trientine (TE) hydrochloride on the levels of methylglyoxal (MG), 3-deoxyglucosone (3-DG), advanced glycation end products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and polyol pathway metabolites along with semicarbazide-sensitive amine oxidase (SSAO) enzyme activity in lenses from streptozotocin-induced diabetic rats. Lens MG and 3-DG levels were significantly higher in diabetic rats than nondiabetic controls, and TE significantly restored the increase of these compounds. Lens argpyrimidine was also increased in diabetic rats as compared with controls and was significantly reduced by TE. Lens SSAO activity and 8-OHdG were also significantly elevated in diabetic rats, and TE suppressed both of them, whereas TE showed no effect on the polyol pathway metabolites. The results indicate that transition metals play a significant role in the formation of MG and 3-DG via oxidative stress and SSAO activity.
Hamada
Yoji
Y
Division of Metabolic Diseases, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. yhama@med.nagoya-u.ac.jp
Nakashima
Eitaro
E
Naruse
Keiko
K
Nakae
Mika
M
Naiki
Mitsuru
M
Fujisawa
Hiroki
H
Oiso
Yutaka
Y
Hotta
Nigishi
N
Nakamura
Jiro
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D006631:Amine Oxidase (Copper-Containing) / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D003300:Copper / Q000378:metabolism*; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009952:Ornithine / Q000031:analogs & derivatives / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011108:Polymers / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014266:Trientine / Q000627:therapeutic use*
D002614:Chelating Agents; D017127:Glycation End Products, Advanced; D011108:Polymers; D011743:Pyrimidines; C107313:argpyrimidine; C024617:polyol; D011765:Pyruvaldehyde; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003847:Deoxyglucose; D009952:Ornithine; D006631:Amine Oxidase (Copper-Containing); C016350:3-deoxyglucosone; D003849:Deoxyguanosine; D014266:Trientine