In vivo treatment with stobadine prevents lipid peroxidation, protein glycation and calcium overload but does not ameliorate Ca2+-ATPase activity in heart and liver of streptozotocin-diabetic rats: comparison with vitamin E

Abstract

Hyperglycemia leads to excess production of reactive oxygen species (ROS), lipid peroxidation and protein glycation that may impair cellular calcium homeostasis and results in calcium sequestration and dysfunction in diabetic tissues. Stobadine (ST) is a pyridoindole antioxidant has been postulated as a new cardio- and neuroprotectant. This study was undertaken to test the hypothesis that the treatment with ST inhibits calcium accumulation, reduces lipid peroxidation and protein glycation and can change Ca2+,Mg2+-ATPase activity in diabetic animals. The effects of vitamin E treatment were also evaluated and compared with the effects of combined treatment with ST. Diabetes was induced by streptozotocin (STZ, 55 mg/kg i.p.). Some of diabetic rats and their age-matched controls were treated orally with a low dose of ST (24.7 mg/kg/day), vitamin E (400-500 IU/kg/day) or ST plus vitamin E for 10 weeks. ST and vitamin E separately produced, in a similar degree, reduction in diabetes-induced hyperglycemia. Each antioxidant alone significantly lowered the levels of plasma lipid peroxidation, cardiac and hepatic protein glycation in diabetic rats but vitamin E treatment was found to be more effective than ST treatment alone. Diabetes-induced increase in plasma triacylglycerol levels was not significantly altered by vitamin E treatment but markedly reduced by ST alone. The treatment with each antioxidant completely prevented calcium accumulation in diabetic heart and liver. Microsomal Ca2+,Mg2+-ATPase activity significantly decreased in both tissues of untreated diabetic rats. ST alone significantly increased microsomal Ca2+,Mg2+-ATPase activity in the heart of normal rats. However, neither treatment with ST nor vitamin E alone, nor their combination did change cardiac Ca2+,Mg2+-ATPase activity in diabetic heart. In normal rats, neither antioxidant had a significant effect on hepatic Ca2+,Mg2+-ATPase activity. Hepatic Ca2+,Mg2+-ATPase activity of diabetic rats was not changed by single treatment with ST, while vitamin E alone completely prevented diabetes-induced inhibition in microsomal Ca2+,Mg2+-ATPase activity in liver. Combined treatment with ST and vitamin E provided more benefits in the reduction of hyperglycemia and lipid peroxidation in diabetic animals. This study describes potential mechanisms on cellular effects of ST in the presence of diabetes-induced hyperglycemia that may delay or inhibit the development of diabetic complications. The use of ST together with vitamin E can better control hyperglycemia-induced oxidative stress.

Furan-induced hepatotoxic and hematologic changes in diabetic rats: the protective role of lycopene

“…The albumin level may decrease in rats as a disorder of the liver function after furan exposure; there are studies confirming that chemicals cause a reduction of albumin and total protein levels (22). In previous studies, researchers observed that diabetes caused an increase in the serum levels of total cholesterol and triglyceride (23). Thus, increased parameters can be due to the effects of diabetes on the permeability of membranes of hepatic cells (24).…”

Effect of Stobadine on Leukocyte Free Radical Generation in Streptozotocin-Diabetic Rats: Comparison with Vitamin E

“…Although it has been reported that stobadine has free radical scavenging properties both in vivo and in vitro [4] and that it inhibits STZ-induced lipid peroxidation [7], the mechanism of inhibition of the effects of diabetes on leukocyte free radical release is not known from the present study. We have shown that stobadine reduced hyperglycemia which may involve the restoration of the leukocyte CL response in our study.…”

“…We have shown that stobadine reduced hyperglycemia which may involve the restoration of the leukocyte CL response in our study. Stobadine has been shown to suppress the STZ-induced elevation of the blood glucose levels in rats [7] and the alloxan-induced hyperglycemia in mice in a dose-and time-dependent manner [13]. It has been demonstrated in a recent study [14] that stobadine was able to restore the enzymatic activities related to pentose phosphate pathway and glutathionedependent metabolism in brain and peripheral organs of diabetic rats.…”

“…; n = 8); (4) diabetic rats treated with both stobadine and vitamin E as given in protocols 2 and 3 (n = 10); (5) untreated control rats (n = 5); (6) control rats treated with stobadine as given in protocol 2 (n = 5); (7) control rats treated with vitamin E as given in protocol 3 (n = 5), and (8) control rats treated with stobadine plus vitamin E as given in protocol 4 (n = 5). The dose regimen of stobadine or vitamin E was chosen according to a previous study [7]. The animals were treated for a period of 10 weeks, beginning 48 h after either vehicle or STZ injection.…”

Antiglycation therapy: Discovery of promising antiglycation agents for the management of diabetic complications

“…However, the exact mechanism(s) of the effects of the both antioxidants on abnormal intracellular calcium regulation of diabetic heart and liver are not fully known. It was also observed that by the using both antioxidants together, hyperglycemia-induced oxidative stress can be controlled effectively (Pekiner et al, 2002).…”