Enhanced menadione cytotoxicity in platelets isolated from streptozotocin-induced diabetic rats.
To study whether chemically induced cytotoxicity occurs in diabetic platelets, platelets isolated from rats made hyperglycemic (diabetic) by a prior intravenous administration of streptozotocin were incubated with menadione and the cytotoxicity was assessed by the amount of lactate dehydrogenase (LDH) released from the menadione exposed platelets as a function of time. Platelets isolated from diabetic rats released greater amount of LDH in response to menadione than those from normal rats. Consistent with this finding, induction of menadione cytotoxicity was not dependent on glutathione depletion, but on greater generation of free radicals in diabetic platelets. Greater sensitivity of diabetic platelets to the menadione-induced cytotoxicity was accompanied by release of serotonin from dense granules, suggesting that this mechanism contributes to cardiovascular diseases in diabetic subjects.
Bae
Ok-Nam
ON
Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinrim-dong San 56-1, 151-742, Seoul, South Korea.
Lee
Joo-Young
JY
Chung
Ga-Young
GY
Chung
Seung-Min
SM
Lee
Moo-Yeol
MY
Yun
Yeo-Pyo
YP
Kim
Young-Chul
YC
Moon
Chang-Kiu
CK
Chung
Jin-Ho
JH
D000818:Animals; D000933:Antifibrinolytic Agents / Q000633:toxicity*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology*; D013997:Time Factors; D024483:Vitamin K 3 / Q000633:toxicity*
D000933:Antifibrinolytic Agents; D005609:Free Radicals; D017382:Reactive Oxygen Species; D012701:Serotonin; D013311:Streptozocin; D024483:Vitamin K 3; D007770:L-Lactate Dehydrogenase; D005978:Glutathione