Protective effect of probucol on alloxan diabetes in rats.
The diabetogenic action of alloxan is known to be attenuated by several oxygen radical scavengers. The present study was conducted to see if probucol, a drug with strong free radical scavenger action, can reduce pancreatic B-cell damage induced by alloxan in male Wistar rats. After 2 weeks of a 1% probucol diet, 50 mg/kg alloxan was intravenously injected in rats (group PA, n = 34). Urine glucose of most of the injected rats not pretreated with probucol (group A, n = 22) was positive, while more than half of the rats of group PA failed to show urine glucose. The blood glucose level in group PA was significantly lower than that in group A (326 +/- 25 vs. 487 +/- 28 mg/dl, P less than 0.001). Histological examination revealed that most of the pancreatic islets of group A were degranulated, whereas a lot of islets remained unaffected in group PA. Thus, the in vivo diabetogenic action of alloxan was reduced by pretreatment with probucol, although the effect was incomplete. This effect can be explained by probucol's strong free radical scavenger action. Since accumulation of free radicals can be an initial step of B-cell damage in animal models of type 1 (insulin-dependent) diabetes, the drug can be useful for the prevention of type 1 diabetes with its long-term clinical history of safety.
Matsushita
M
M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yoshino
G
G
Iwai
M
M
Matsuba
K
K
Morita
M
M
Iwatani
I
I
Yoshida
M
M
Kazumi
T
T
Baba
S
S
D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D006029:Glycosuria; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology*; D008297:Male; D010636:Phenols / Q000627:therapeutic use*; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D010636:Phenols; D000496:Alloxan; D011341:Probucol