Abstract: |
The present study was carried out to explore a novel strategy with the hypothesis that the combined treatment
with standard antidiabetic drug metformin (MET) and chitosan stabilized nanoparticles (CTS-Se-NPs) may have a
potential role on insulin level, hepatic damage and apoptosis, and cardiac injury markers of type 2 diabetes
mellitus (T2DM) in rat model. T2DM was induced by a high fat diet (HFD) for 8 weeks and a single injection of a
low dose streptozotocin (STZ) (35 mg/kg) in Sprague Dawley rats. A total number of one hundred rats were
divided into five groups; the first served as a control (non-diabetic) group and the other four groups served as
diabetic rats. The treatments were even mono or combined therapy by CTS-Se-NPs and/or MET for 8 weeks. A
group was given only MET (500 mg/kg bw/day), another was administered only CTS-Se-NPs at a dose of 2 mg
se/kg/day, while the last group was given both of them (co-treated group). Biochemical, molecular and histopathological
analyses were conducted to figure out the efficiency of the treatment by the monotherapeutic mode
or combination therapy on the insulin level, oxidants/antioxidants status, inflammatory mediators, hepatic and
cardiac injury biomarkers and apoptotic/anti-apoptotic gene expressions. Our results indicated that HFD/STZinduced
toxic effects on the serum, hepatic and cardiac tissues including a remarkable elevation of the oxidative
and inflammatory mediators, and up-regulation of the apoptotic genes (Bax, Caspase-3, Fas, Fas-L)
expression. Histologically, the heart tissue revealed various degenerative, vascular and inflammatory alterations
characteristic to murine cardiomyopathy. Besides, livers from HFD-STZ-treated rats showed numerous
cytotoxic, circulatory and inflammatory alterations. Combined therapy with MET and CTS-Se-NPs resulted in a
better remarkable anti-diabetic effect demonstrated by substantial decreases in fasting blood glucose and insulin
levels, and elevated with up-regulation of anti-apoptotic gene (BCL-2) and down-regulation of apoptotic genes
after 8 weeks of treatment than that revealed in the monotherapeutic strategy. In addition, it ameliorated the
damage of cardiac and hepatic tissues and reduced lipid accumulation, and pro-inflammatory cytokines levels
and restored the antioxidant capacity. It could be concluded that, the combined strategy applied in the current
study have a potential role to limit the diabetic complications and restore insulin resistance to a higher extent
than monotherapeutic strategy and could be considered a promising therapeutic alternative in T2DM rat mode
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