Melatonin is more effective than taurine and 5-hydroxytryptophan against hyperglycemia-induced kidney-cortex tubules injury.
The antioxidative effects of melatonin (Mel), 5-hydroxytryptophan (5-HTP) and taurine (TAU) on hyperglycemia-induced oxidative stress was investigated in primary cultures of kidney-cortex tubule cells grown in metabolically and hormonally defined medium. In the presence of 30 mm glucose (hyperglycemic conditions), cell viability was decreased by about 35% in comparison with that estimated in the glucose-depleted medium probably as a result of induction of apoptosis, as concluded from: (i) chromatin condensation and DNA fragmentation assays, (ii) a significant enhancement of reactive oxygen species (ROS) production, (iii) 8-hydroxydeoxyguanosine (8-OHdG) generation, (iv) an increased protein peroxidation and (v) a decline of reduced glutathione (GSH) levels leading to a disturbed glutathione redox state. The addition of 100 microm Mel to the hyperglycemic medium resulted in a twofold decrease in both 8-OHdG accumulation and protein peroxidation as well as restoration of the control intracellular ROS levels accompanied by a substantial increase in GSH/oxidized glutathione (GSSG) ratio due to a decline in GSSG content. ROS elimination was also achieved in the presence of 1 mm TAU which diminished protein and DNA injuries by about 25% and 30%, respectively. On the contrary, the action of 100 microm 5-HTP on ROS level, 8-OHdG generation, protein peroxidation and GSH/GSSG ratio was negligible. Thus, in contrast to 5-HTP and TAU, Mel might be considered as beneficial for diabetes therapy, particularly in terms of reduction of hyperglycemia-induced kidney injury.
Derlacz
Rafal A
RA
Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, Warsaw University, Warsaw, Poland.
Sliwinska
Malgorzata
M
Piekutowska
Anna
A
Winiarska
Katarzyna
K
Drozak
Jakub
J
Bryla
Jadwiga
J
D006916:5-Hydroxytryptophan / Q000502:physiology*; D000818:Animals; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000502:physiology*; D009924:Organ Culture Techniques; D011817:Rabbits; D013654:Taurine / Q000502:physiology*
D013654:Taurine; D006916:5-Hydroxytryptophan; D008550:Melatonin