The Hepatoprotective Effect of Jaboticaba Peel Powder in a Rat Model of Type 2 Diabetes Mellitus Involves the Modulation of Thiol/Disulfide Redox State through the Upregulation of Glutathione Synthesis.

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzyme δ-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects.

Hypercholesterolemia and oxidative stress have been implicated in the pathophysiology of atherosclerosis and coronary artery disease. We investigated whether the carotenoid bixin (BIX) may reduce oxidative damage, inflammatory response, and the atherosclerotic lesion induced by hypercholesterolemia in rabbits. Rabbits received regular chow (control) or a hypercholesterolemic diet (0.5% cholesterol) alone or supplemented with BIX (10, 30 or 100 mg/kg body weight, b.w.) or simvastatin (15 mg/kg b.w.) for 60 days. Treatment with BIX or simvastatin reduced the atherosclerotic lesions in cholesterol-fed rabbits (up to 55 and 96% reduction, respectively). This protective effect of BIX was accompanied by decrease in the levels of tumor necrosis factor alpha by 15%, interleukin 6 by 19%, lipid peroxidation by 60%, non-high-density lipoprotein cholesterol (non-HDL-C) by 37%, and triglycerides by 41%. BIX increased by 160% the HDL-C levels and decreased by 67% the atherogenic index of hypercholesterolemic rabbits. In atherosclerotic rabbits, the non-protein thiol groups content and the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase were increased in the aortic tissue, whereas paraoxonase activity was reduced in the serum. All these changes were completely prevented by BIX or simvastatin treatment. These results demonstrate that BIX reduces the extent of atherosclerotic lesions and this effect was associated with the decrease in oxidative stress, inflammatory response, and improvement of dyslipidemia, which were most effectively controlled after treatment with 10-30 mg BIX/kg b.w. BIX consumption may, therefore, be an adjuvant to prevent atherosclerosis reducing risk factors for coronary diseases.

Bixin and norbixin have opposite effects on glycemia, lipidemia, and oxidative stress in streptozotocin-induced diabetic rats.

The present study investigated the effects of oral administration of annatto carotenoids (bixin (BIX) and norbixin (NBIX)) on glucose levels, lipid profiles, and oxidative stress parameters in streptozotocin (STZ)-induced diabetic rats. Animals were treated for 30 days in the following groups: nondiabetic control, diabetic vehicle, diabetic 10 mg/kg BIX, diabetic 100 mg/kg BIX, diabetic 10 mg/kg NBIX, diabetic 100 mg/kg NBIX, diabetic metformin, and diabetic insulin. Blood glucose, LDL cholesterol, and triglyceride levels were reduced in the diabetic rats treated with BIX. BIX treatment prevented protein oxidation and nitric oxide production and restored superoxide dismutase activity. NBIX treatment did not change most parameters assessed, and at the highest dose, it increased LDL cholesterol and triglycerides levels and showed prooxidant action (increased protein oxidation and nitric oxide levels). These findings suggested that BIX could have an antihyperglycemic effect, improve lipid profiles, and protect against damage induced by oxidative stress in the diabetic state. Because NBIX is a water-soluble analog of BIX, we propose that lipophilicity is crucial for the protective effect of annatto carotenoids against streptozotocin-induced diabetes.

Acute exposure to low lead levels and its implications on the activity and expression of cytosolic thioredoxin reductase in the kidney.

Renal thioredoxin reductase-1 (TrxR-1) activity is stimulated at lead doses lower than that necessary to inhibit δ-aminolevulinate dehydratase activity (δ-ALA-D), which is a classical early biomarker of lead effects. Thus, we hypothesized that the activity of TrxR-1 could be a more sensitive early indicator of lead effects than is δ-ALA-D. To evaluate this hypothesis, we assessed the blood and renal TrxR-1 activity and its gene expression along with biomarkers of oxidative damage, antioxidant enzyme activities and biomarkers of lead exposure in rats acutely exposed to lead. A histopathological analysis was performed to verify renal damage. The increase in renal TrxR-1 activity paralleled the increase in the blood and renal lead levels at 6, 24 and 48 hr after the exposure to 25 mg/kg lead acetate (p < 0.05), whereas its expression was increased 24 and 48 hr after exposure. These effects were not accompanied by oxidative or tissue damage in the kidneys. Blood TrxR-1 activity was not affected by lead exposure (up to 25 mg/kg). Erythrocyte δ-ALA-D activity was inhibited 6 hr after the exposure to 25 mg/kg lead acetate (p < 0.05) but recovered thereafter. Renal δ-ALA-D activity decreased 24 and 48 hr after the exposure to 25 mg/kg lead acetate. There were no changes in any parameters at lead acetate doses <25 mg/kg. Our results indicate that blood TrxR-1 activity is not a suitable indicator of lead effects. In contrast, the increase in renal TrxR-1 expression and activity is implicated in the early events of lead exposure, most likely as a protective cellular mechanism against lead toxicity.