Evaluation of Antioxidant Therapeutic Value of ACE Inhibitor as Adjunct Therapy on Type 2 Diabetes Mellitus Patients with Cardiovascular Disease.

Diabetes mellitus (DM) is believed to promote oxidative stress, which potentially provokes and accelerates complications in conditions such as atherosclerotic cardiovascular, peripheral arterial, and cerebrovascular diseases. In this study, we evaluated the antioxidant therapeutic value of adding an angiotensin-converting enzyme (ACE) inhibitor-a low dose of captopril-as adjunct therapy to the treatment regimen of Type 2 diabetes mellitus (T2DM). Participants were distributed among two different groups: control and treated. T2DM patients in the treated group (group 2) were given a supplement of the ACE inhibitor capotopril, 12.5 mg/day, in addition to standard treatment. All subjects were interviewed for clinical examination. All patients in group 2 were re-examined monthly for 3 months to evaluate FBS, HbA1c, MDA, total GSH, reduced GSH, GSSG, and ox-LDL. All parameters were repeated for patients in group 2 after 1 and 3 months. The study showed improvements in the glycemic and oxidative stress status with the addition of a low dose of captopril-not very prominent but statistically significant. Reduced GSH decreased by 73.6% (P = 0.016) and the TBARS level was decreased by 58.3% (P = 0.018) after 3 months of treatment, while ox-LDL was decreased by 26.4% (P = 0.036) at the end of treatment. In summary, the clinical improvements in the disease indices toward normal levels make the use of low doses of ACE inhibitors as adjunct therapy in T2DM worth pursuing. Thus, investigations directed at preventing or protecting against oxidative damage may open a new window for treatment of diabetes mellitus.

Reduction of Cholesterol and Fasting Blood Sugar Levels by One Month Supplementation of Fresh Garlic in Diabetic Libyan Patients: A Double Blind, Baseline Controlled Study

Background: The therapeutic effects of fresh garlic remain controversial. The aim of this study is to investigate whether supplementation of fresh garlic could improve blood glucose and cholesterol profile in Libyan diabetic patients with moderate blood cholesterol.Methods:Forty-six diabetic patients were randomly assigned to either fresh garlic alone (≈2 grams/day), or fresh garlic in combination with glibenclamide taken on an empty stomach every morning for a month. Serum blood glucose, cholesterol and blood pressure were measured before starting treatment and after the end of the treatment period.Results: Fresh garlic alone was able to decrease the mean serum cholesterol levels by 26 mg/dl (84% of the original base values), while the combination of fresh garlic and glibenclamide produced a 28 mg/dl decrease in the mean serum cholesterol (85% of the original base values). Fresh garlic alone was able as well to decrease the mean blood glucose levels by 20 mg/dl (85% of the original base values), while the combination of fresh garlic and glibenclamide produced a 60 mg/dl decrease in the serum glucose levels (72% of the original base values). Neither treatment had a significant effect on the mean systolic or diastolic blood pressures after 30 days of treatment.Conclusion: Administration of fresh garlic every morning for a month significantly reduced the blood cholesterol and fasting blood glucose levels in diabetic patients. Thus administering dietary fresh garlic daily to diabetic patients might have cardio-protective effects on diabetic patients

Aldolase B knockdown prevents high glucose-induced methylglyoxal overproduction and cellular dysfunction in endothelial cells.

We used cultured endothelial cells as a model to examine whether up-regulation of aldolase B and enhanced methylglyoxal (MG) formation play an important role in high glucose-induced overproduction of advanced glycosylation endproducts (AGEs), oxidative stress and cellular dysfunction. High glucose (25 mM) incubation up-regulated mRNA levels of aldose reductase (an enzyme converting glucose to fructose) and aldolase B (a key enzyme that catalyzes MG formation from fructose) and enhanced MG formation in human umbilical vein endothelial cells (HUVECs) and HUVEC-derived EA. hy926 cells. High glucose-increased MG production in EA. hy926 cells was completely prevented by siRNA knockdown of aldolase B, but unaffected by siRNA knockdown of aldolase A, an enzyme responsible for MG formation during glycolysis. In addition, inhibition of cytochrome P450 2E1 or semicarbazide-sensitive amine oxidase which produces MG during the metabolism of lipid and proteins, respectively, did not alter MG production. Both high glucose (25 mM) and MG (30, 100 µM) increased the formation of N(ε)-carboxyethyl-lysine (CEL, a MG-induced AGE), oxidative stress (determined by the generation of oxidized DCF, H(2)O(2), protein carbonyls and 8-oxo-dG), O-GlcNAc modification (product of the hexosamine pathway), membrane protein kinase C activity and nuclear translocation of NF-κB in EA. hy926 cells. However, the above metabolic and signaling alterations induced by high glucose were completely prevented by knockdown of aldolase B and partially by application of aminoguanidine (a MG scavenger) or alagebrium (an AGEs breaker). In conclusion, efficient inhibition of aldolase B can prevent high glucose-induced overproduction of MG and related cellular dysfunction in endothelial cells.

The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats.

BACKGROUND: Our previous studies have shown that broccoli sprouts high in the glucosinolate glucoraphanin decreases renal and vascular oxidative stress and inflammation as well as blood pressure in spontaneously hypertensive stroke-prone (SHRSP) rats. The objective of this study was to determine whether the metabolite of glucoraphanin, sulforaphane, was responsible for this improved blood pressure and whether this is associated with normalization of renal methylated DNA. METHODS: Sulforaphane was given by gavage to SHRSP and Sprague Dawley (SD) rats over 4 months and blood pressure measured under anesthesia just before euthanasia. Renovascular morphology was determined by histology and methylated deoxycytosine levels analyzed using high-performance liquid chromatography. RESULTS: Mean arterial pressure was 20% higher in vehicle-treated SHRSP when compared to SD. Sulforaphane administration to SHRSP improved blood pressure and lowered this difference to 11%. Vehicle-treated SHRSP had significantly increased wall:lumen ratios in renal arteries, increased numbers of vascular smooth muscle cells (VSMCs), increased renal protein nitration, and decreased (11%) renal DNA methylation compared to SD. Sulforaphane administration to SHRSP significantly lowered arterial wall:lumen ratio by 35%, reduced the number of VSMCs, reduced the level of protein nitration, and increased methylated deoxycytosine levels by 14%. CONCLUSIONS: Sulforaphane administration rectified pathological abnormalities in SHRSP kidneys and significantly improved blood pressure. This was associated with normalization of global kidney DNA methylation suggesting that DNA methylation could be associated with hypertension.

Oxidative stress and aging: is methylglyoxal the hidden enemy?

Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.

Antiischemic effects of topiramate in a transient global forebrain ischemia model: a neurochemical, histological, and behavioral evaluation.

The mechanisms of action of the anticonvulsant topiramate (TPM) are indicative of a potential benefit during cerebral ischemia. TPM was studied in a transient global forebrain ischemia (TGFI) model in gerbils in which 40 mg/kg was administered before or after TGFI. Control groups were administered 0.9% normal saline similarly. The evaluation consisted of neurochemical, histological, and functional analyses. The data obtained indicates that unlike the focal cerebral ischemia model, TPM is not neuroprotective in TGFI. The difference in effect, which may be due to the difference in species or the type of ischemia, points to the need for caution when extrapolating animal data from this drug to humans.