Xenobiotics constantly influence biological systems through several means of interaction. These interactions are disturbed in type 2 diabetes, with implications for disease outcome. We aimed to study the implications of such disturbances on type 2 diabetes and rice consumption, the results of which could affect management of the disease in developing countries. In a type 2 diabetic rat model induced through a combination of high fat diet and low dose streptozotocin injection, up-regulation of xenobiotic metabolism genes in the diabetic untreated group was observed. Xenobiotic metabolism genes were upregulated more in the white rice (WR) group than the diabetic untreated group while the brown rice (BR) group showed significantly lower expression values, though not as effective as metformin, which gave values closer to the normal non-diabetic group. The fold changes in expression in the WR group compared to the BR group for Cyp2D4, Cyp3A1, Cyp4A1, Cyp2B1, Cyp2E1, Cyp2C11, UGT2B1, ALDH1A1 and Cyp2C6 were 2.6, 2, 1.5, 4, 2.8, 1.5, 1.8, 3 and 5, respectively. Our results suggest that WR may upregulate these genes in type 2 diabetes more than BR, potentially causing faster drug metabolism, less drug efficacy and more toxicity. These results may have profound implications for rice eating populations, constituting half the world's population.
Hyperglycemia exerts toxic effects on the pancreatic beta-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage.
Vitamin E is composed of various subfamilies that include tocopherols and tocotrienols. These compounds have antioxidant properties but differ in structure, dietary source and potency. In this study we evaluated the efficacy of alpha-tocopherol as an antioxidant and its role in wound closure in normal and streptozotocin-induced diabetic rats. The healing of 6 cm linear incisions created on the back of each male Sprague-Dawley rat (250-300 g) was monitored by measuring the length of the wounds daily. The rats were divided into two categories; normal and streptozotocin-induced diabetic rats. For each category, the animals were further divided into two groups; those untreated and those receiving 200 mg/kg bodyweight alpha-tocopherols daily by oral gavage. All rats were fed standard food and water ad libitum. Blood samples were taken at 0, 5 and 10 days after the wounds were created for the determination of malondialdehyde levels and red cell superoxide dismutase, catalase and glutathione peroxidase activities. The results showed that alpha-tocopherol reduced plasma malondialdehyde levels, increased glutathione peroxidase activity and accelerated the rate of wound closure in treated rats.
This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.
One vital therapeutic approach for the treatment of type 2 diabetes mellitus is the use of agents that can decrease postprandial hyperglycaemia by inhibiting carbohydrate digesting enzymes. The present study investigated the effects of bioassay-guided extract and fractions of the dried fruit pericarp of Phaleria macrocarpa, a traditional anti-diabetic plant, on α-glucosidase and α-amylase, in a bid to understand their anti-diabetic mechanism, as well as their possible attenuation action on postprandial glucose increase.
Diabetes is associated with endothelial dysfunction, which is characterized by impaired endothelium-dependent relaxations. The present study aimed to examine the role of nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH), in the relaxation of ventral tail arteries of rats under diabetic conditions. Relaxations of tail arteries of control and diabetic rats were studied in wire myograph. Western blotting and immunostaining were used to determine the presence of proteins. Acetylcholine-induced relaxations were significantly smaller in arteries of diabetic compared to control rats (Rmax; 70.81 ± 2.48% versus 85.05 ± 3.15%). Incubation with the combination of non-selective cyclooxygenase (COX) inhibitor, indomethacin and potassium channel blockers, TRAM 34 and UCL 1684, demonstrated that NO-mediated relaxation was attenuated significantly in diabetic compared to control rats (Rmax; 48.47 ± 5.84% versus 68.39 ± 6.34%). EDH-type (in the presence of indomethacin and NO synthase inhibitor, LNAME) and prostacyclin-mediated (in the presence of LNAME plus TRAM 34 and UCL 1684) relaxations were not significantly reduced in arteries of diabetic compared to control rats [Rmax: (EDH; 17.81 ± 6.74% versus 34.16 ± 4.59%) (prostacyclin; 15.85 ± 3.27% versus 17.23 ± 3.75%)]. Endothelium-independent relaxations to sodium nitroprusside, salbutamol and prostacyclin were comparable in the two types of preparations. Western blotting and immunostaining indicated that diabetes diminished the expression of endothelial NO synthase (eNOS), while increasing those of COX-1 and COX-2. Thus, since acetylcholine-induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction.
The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress.
Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.