Norbixin, a natural dye that improves serum lipid profile in rabbits and prevents LDL oxidation.

We hypothesized that norbixin, which is a carotenoid used as an orange/red natural food coloring additive, has anti-atherogenic properties. An in vitro oxidation assay with human LDL and a rabbit model of atherosclerosis were used to test this hypothesis. Norbixin inhibited the oxidation of isolated human LDL in a concentration-dependent manner. In the in vivo assay, rabbits were fed with a regular chow (control) or an atherogenic diet (0.5% cholesterol) alone or supplemented with norbixin (10, 30 or 100 mg/kg b.w.) for 60 days. Norbixin supplementation (30 and 100 mg/kg b.w.) increased HDL levels and reduced triglyceride levels and the atherogenic index of rabbits. This effect was associated with the decrease of serum levels of oxidized LDL, oxidized LDL antibodies and aortic tissue levels of lipid and protein oxidation in the atherogenic rabbits supplemented with norbixin. Atherogenic diet increased enzymatic (superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase-1) and non-enzymatic (non-protein thiol groups content) antioxidant defense systems in the aortic tissue but reduced the activity of paraoxonase-1 in the serum. All these changes were prevented by norbixin supplementation (10, 30 and 100 mg/kg b.w.). These results suggest that norbixin has atheroprotective potential by improving serum lipid profile and preventing oxidative modifications of circulating LDL and aortic tissue. Norbixin may, therefore, be beneficial in the control of atherosclerosis risk factors and can be further investigated as a candidate to be used not only as a functional food ingredient but also for therapeutic applications and in the nutraceutical industry.

Bioactivity, bioavailability, and gut microbiota transformations of dietary phenolic compounds: implications for COVID-19.

The outbreak of mysterious pneumonia at the end of 2019 is associated with widespread research interest worldwide. The coronavirus disease-19 (COVID-19) targets multiple organs through inflammatory, immune, and redox mechanisms, and no effective drug for its prophylaxis or treatment has been identified until now. The use of dietary bioactive compounds, such as phenolic compounds (PC), has emerged as a putative nutritional or therapeutic adjunct approach for COVID-19. In the present study, scientific data on the mechanisms underlying the bioactivity of PC and their usefulness in COVID-19 mitigation are reviewed. In addition, antioxidant, antiviral, anti-inflammatory, and immunomodulatory effects of dietary PC are studied. Moreover, the implications of digestion on the putative benefits of dietary PC against COVID-19 are presented by addressing the bioavailability and biotransformation of PC by the gut microbiota. Lastly, safety issues and possible drug interactions of PC and their implications in COVID-19 therapeutics are discussed.

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.

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.

Astaxanthin prevents changes in the activities of thioredoxin reductase and paraoxonase in hypercholesterolemic rabbits.

This study explored the effects of the antioxidant astaxanthin on paraoxonase and thioredoxin reductase activities as well as on other oxidative stress parameters and on the lipid profile in hypercholesterolemic rabbits. Rabbits were fed a standard or a hypercholesterolemic diet alone or supplemented with 50, 100 and 500 mg/100 g of astaxanthin for 60 days. Antioxidant enzymes activities, lipid profile and oxidative stress markers were evaluated in the serum. The hypercholesterolemic diet increased lipids, including unsaturated fatty acids level, whereas it decreased saturated fatty acids level. These changes were accompanied by increased levels of oxidized low-density lipoprotein and oxidized low-density lipoprotein antibodies, as well as lipid and protein oxidation. Astaxanthin (100 and 500 mg/100 g) prevented hypercholesterolemia-induced protein oxidation, whereas 500 mg/100 g of astaxanthin decreased protein oxidation per se. The activities of superoxide dismutase and thioredoxin reductase were enhanced, whereas paraoxonase activity was inhibited in hypercholesterolemic rabbits. All astaxanthin doses prevented changes in thioredoxin reductase and paraoxonase activities. This effect was not related to a direct effect of astaxanthin on these enzymes, because in vitro astaxanthin enhanced thioredoxin reductase and had no effect on paraoxonase activity. Astaxanthin could be helpful in cardiovascular diseases by restoring thioredoxin reductase and paraoxonase activities.

Astaxanthin reduces oxidative stress, but not aortic damage in atherosclerotic rabbits.

We evaluated whether carotenoid astaxanthin (ASX) could prevent oxidative and atherosclerotic damage in rabbits. Rabbits received regular chow (control) or an atherogenic diet (1% cholesterol) alone or supplemented with 50, 100, and 500 mg% ASX for 60 days (n = 5-9 per group). The atherogenic diet increased the serum cholesterol levels and the ratio of the intima/media area in the aortic arch. These changes were not prevented by ASX. Atherosclerotic rabbits showed increased aortic lipid peroxidation and nonprotein thiol group (NPSH) levels along with inhibition of glutathione peroxidase (GSH-Px). All ASX doses attenuated lipid peroxidation and the increase in NPSH but not the inhibition of GSH-Px. Aortic superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TrxR) activities were enhanced in atherosclerotic rabbits. Although all ASX doses prevented the increase in SOD activity, only 100 and 500 mg% ASX prevented the increase in CAT activity. Furthermore, these same doses partially prevented the increase in TrxR activity, while 50 mg% ASX completely prevented the effects of the atherogenic diet on this enzyme. However, ASX did not attenuate the hypercholesterolemia or the atherosclerotic lesions caused by the atherogenic diet at any of the doses evaluated. Our results indicate that although ASX did not prevent hypercholesterolemia or atherosclerotic lesions, it could play a beneficial role by preventing lipid peroxidation and changes in antioxidant enzyme activities.

Effects of bone disease and calcium supplementation on antioxidant enzymes in postmenopausal women.

OBJECTIVES: The study was aimed at investigating the effects of osteopenia and calcium supplementation on antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) in postmenopausal women. DESIGN AND METHODS: Postmenopausal women (n=75) were divided into two groups, control (no bone disease) and osteopenia, according to their bone mineral density. Each group was still divided into calcium-supplemented and nonsupplemented sub-groups. Antioxidant enzyme activities were determined in whole blood using spectrophotometric methods. RESULTS: CAT and SOD activities were not different among the studied groups. However, GPx activity was significantly higher in osteopenia groups as compared to control groups. Calcium supplementation had no effect on the parameters evaluated. Bone mineral density was negatively correlated with GPx activity (p<0.05). CONCLUSIONS: Increased GPx activity could be interpreted as a defense response to counteract the overproduction of reactive oxygen species in women with osteopenia, and this effect was not prevented by calcium supplementation.

Effect of lead acetate on cytosolic thioredoxin reductase activity and oxidative stress parameters in rat kidneys.

Oxidative stress has been suggested to be an important molecular mechanism of toxic effects of lead in the kidney. Thioredoxin reductase-1 is a selenoprotein involved in many cellular redox processes. This study evaluated the effect of acute and chronic exposure intraperitoneally to lead acetate on thioredoxin reductase-1 activity and on other oxidative stress parameters in the rat kidney, as well as on indicators of renal function commonly used to assess lead poisoning. Acute exposure to 25 mg/kg lead acetate increased superoxide dismutase and thioredoxin reductase-1 activity (after 6, 24 and 48 hr), while exposure to 50 mg/kg lead acetate increased catalase activity (after 48 hr) and inhibited delta-aminolevulinate dehydratase activity (after 6, 24 and 48 hr) in the kidney (P < 0.05). Chronic exposure (30 days) to 5 mg/kg lead acetate inhibited delta-aminolevulinate dehydratase and increased glutathione S-transferase, non-protein thiol groups, catalase, thioredoxin reductase-1 and uric acid plasma levels, while exposure to 25 mg/kg lead acetate reduced body weight and delta-aminolevulinate dehydratase, but increased glutathione S-transferase, non-protein thiol groups and uric acid plasma levels (P < 0.05). No changes were observed in thiobarbituric acid reactive substances, glutathione peroxidase, creatinine or inorganic phosphate levels after either acute or chronic exposure. Our results suggest that thioredoxin reductase-1 may be an early indicator of acute exposure to low lead doses.

Effect of lycopene on nephrotoxicity induced by mercuric chloride in rats.

Oxidative stress is an important molecular mechanism for kidney injury in mercury poisoning. We studied lycopene, a potent carotenoid found in tomatoes due to its large antioxidant properties, and also evaluated the ability of lycopene to prevent HgCl(2) nephrotoxicity. Rats were injected with HgCl(2) (0 or 5 mg/kg body weight, subcutaneously) 6 hr after lycopene administration (0, 10, 25 or 50 mg/kg by gavage) and were killed 12 hr after HgCl(2) exposure. HgCl(2)-induced inhibition of delta-aminolevulinate dehydratase activity (approximately 35%) and increase of lipid peroxidation in kidney (approximately 37%) were prevented by lycopene. However, lycopene did not prevent the increase of plasma creatinine levels (approximately 123%) and renal tubular necrosis induced by HgCl(2). Glutathione peroxidase and catalase activities were enhanced (approximately 71% and approximately 41%), while superoxide dismutase activity was depressed (approximately 44%) in HgCl(2)-treated rats when compared to control and these effects were prevented by lycopene. Our results indicate that although lycopene did not prevent HgCl(2)-induced renal failure, it could play a beneficial role against HgCl(2) toxicity by preventing lipid peroxidation and changes in the activity of delta-aminolevulinate dehydratase and antioxidant enzymes.