Effect of nutrient antioxidants on oxidative stress indicators in patients with alopecia areata

People with alopecia areata lose their scalp hair in smooth round patches typically causing bald spots about an inch (2cm) across. Recently Al-Jaff et al demonstrate the association of free radicals in the pathogenesis of alopecia areata, and the role of nutrient antioxidants in protecting the immune system from the damaging effect of these radicals.Any imbalances between free radical production and antioxidant deficiency can result in an injury. This clinical study designed to study the role of nutrient antioxidants in protecting the body from damaging effect of radicals and the effect of two month treatment with antioxidants (vitamin A, E, &C) on oxidative stress variable levels and their effect on rate of hair growth in patients with alopecia areata. Treatment with antioxidants significantly elevated body antioxidant defenses component levels, increased Zn levels and decreased Cu levels and corrected the inbalance in these trace metals metabolism in alopecia after 1and 2 months of treatment compared to pretreatment values. The most important point is the clinical significance of antioxidants in improving the hair response of patients with alopecia areata; this may be due to an inhibition of oxidative stress associated with the state of the disease

Alterations in the blood glucose, serum lipids and renal oxidative stress in diabetic rats by supplementation of onion (Allium cepa. Linn)

This study examined the anti-diabetic effect of onion (Allium cepa. Linn) in the streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet or supplemented with onion powder (7% w/w) and diabetic rats fed control diet or supplemented with onion powder. Diabetes was induced by a single injection of STZ (60 mg/kg, ip) in citrate buffer. The animals were fed each of the experimental diet for 5 weeks. Blood glucose levels of rats supplemented with onion were lower than those of rats fed control diet in the diabetic rats. Onion also decreased the total serum lipid, triglyceride, and atherogenic index and increased HDL-cholesterol/total cholesterol ratio in the diabetic rats. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were high in the diabetic rats compared to normal rats and reverted to near-control values by onion. These results indicate that onion decreased blood glucose, serum lipid levels and reduced renal oxidative stress in STZ-induced diabetic rats and this effect might exert the anti-diabetic effect of onion

Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition

<p>Abstract</p> <p>Background</p> <p>Curcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction.</p> <p>Methods</p> <p>Diabetes (DM) was induced in rats by streptozotocin (STZ). Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII) were examined by hydroethidine and immunofluorescence, respectively.</p> <p>Results</p> <p>The dilatory response to acetylcholine (ACh) significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP) was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively) of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O₂^●-) production. O₂^●-production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished.</p> <p>Conclusion</p> <p>Therefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.</p

Oxygen free radical scavenging systems in clinical and experimental (chemical and spontaneous) diabetes mellitus

The extent to which endogenous free radical-scavenging defense mechanisms are involved in experimental and human diabetes was investigated in various tissues of animals with chemically-induced or spontaneous diabetes (BB Wistar rats) and in erythrocytes of patients with either Type I or Type II diabetes. Diabetes was induced in female Wistar rats using alloxan (ALX) or streptozotocin (STZ), each administered in a dose of 50 mg/kg body wt., intravenously. The present study also included a group -of animals in which body wt. loss was induced by food-deprivation for 72 h. The effects of pharmacological interventions (insulin or allopurinol (ALP)), on these processes were also investigated in chemically-induced diabetes., The activities of catalase (CAT), CuZn-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-PX) and glutathione reductase (GSSG-RD) as well as levels of reduced glutathione (GSH) were examined in heart, pancreas, liver and kidney as well as in erythrocytes. Erythrocytes were also examined for their susceptibility to in vitro oxidative stress induced by hydrogen peroxide (H₂0₂). Criteria studied in this regard were GSH-depletion and malondi-aldehyde (MDA) production (an index of lipid peroxidation). The results obtained showed that tissue antioxidant systems are altered in experimental diabetes and that the magnitude of the alterations increased with the degree of body weight loss. Furthermore, the duration of hypoinsulinemia might contribute to the nature of alterations in antioxidant mechanisms. The complex patterns of the alterations observed varied from one tissue to another and may be the result of compensatory increases, usually involving enzymes whose activity in the particular tissue may be limiting, and direct inhibitory effects of endogenous oxidants on the enzymatic components of tissue antioxidant systems. The ability of insulin (9-12 U/kg body wt., subcutaneously) to reverse the many similar alterations of tissue antioxidant enzymes in diabetes induced by either STZ or ALX suggests that these changes are more likely attributable to hypoinsulinemia rather than to direct effects of either diabetogenic drug. The above-mentioned effects indicate that insulin can markedly influence tissue antioxidant status. However, the reason for the persistence of decreased CuZn-SOD activity in both liver and kidney of ALX-diabetic rats after 12 wk of treatment with insulin is not clear at present, and requires further investigation to determine whether this reflects the presence of a residual deficit in tissue antioxidant processes in liver and kidney despite insulin treatment, or whether it is the result of a direct effect exerted by ALX. Acute ALP administration (50 mg/kg body wt., intraperitoneally) was associated with reductions in ketonuria and early mortality among ALX-diabetic rats, and long-term ALP treatment (1.9 mg/day in drinking water) resulted in a normalization of renal CuZn-SOD activity in these animals. Comparable (although not identical) changes in tissue antioxidant status are present in insulin-dependent spontaneously diabetic BB (ISDBB) rats and in animals made diabetic by STZ or ALX administration. Our data also demonstate that the alterations in tissue GSH levels characterizing ALX-diabetes more closely paralleled changes seen in the ISDBB rat than did those in the diabetic state induced by STZ. If the alterations in antioxidant status in uncontrolled chemically-induced diabetes are attributable to a lack of insulin, the observed changes in ISDBB rats are suggestive of sub-optimal insulin therapy in these animals. The results obtained from BB rats demonstrate two types of alterations in antioxidant status: strain-related differences (increased CAT activity in pancreas and decreased GSH levels in pancreas and liver of both ISDBB and their non-diabetic littermates (NDLM)) and diabetes-related changes (mani- fested by an increase in cardiac GSH content and increases in activities of cardiac CAT and GSSG-RD, pancreatic CuZn-SOD and GSSG-RD, and renal GSH-PX). Whether or not these "strain-related" alterations in antioxidant status increase the susceptibility of these animals to developing diabetes remains unknown. Certain alterations were observed in red cells from diabetic patients and from animals with experimental diabetes suggesting that these alterations are more likely to be diabetes-related than species-dependent. Red cells in chemically-induced and clinical diabetes showed an increased resistance to peroxide-induced depletion of GSH, an effect attributed to hyperglycemia, which results in an increased supply of NADPH through the hexose monophosphate shunt for regeneration of GSH from GSSG via the GSSG-RD system. However, the susceptibility of red cells from diabetic patients and animals to lipid peroxidative damage was increased as reflected in augmented MDA production. In addition, insulin treatment did not normalize MDA production in red cells subjected to oxidative challenge and vigorous insulin treatment in both ALX- and STZ-diabetic rats resulted in a markedly decreased MDA production in response to H₂0₂. Moreover, GSSG-RD activity of red cells was increased in both uncontrolled and insulin-treated diabetic animals as well as in diabetic patients. However, some differences in erythrocyte antioxidant enzymes were also observed in erythrocytes from diabetic subjects and animals. For example, diabetic patients showed an increased activity of CuZn-SOD, while erythrocytes from diabetic animals showed no alterations in the activity of this enzyme. Erythrocyte membrane NADH-dehydrogenase activity was increased only in diabetic patients with Type I diabetes, but not in Type II diabetes or in diabetic animals. Erythrocytes from ALX- and STZ-diabetic animals showed an increase in the activity of GSH-PX and those from NDLM BB rats showed a decrease in CAT activity, alterations that were not observed in human diabetes. Finally, as far as antioxidant defense mechanisms are concerned, our results suggest that diabetes is associated with some common alterations in these mechanisms regardless of the model (chemically-induced versus the spontaneous type of diabetes) or the species used (animal versus human diabetes). Some of these alterations seem to be influenced by the degree of diabetic control, while others are apparently independent of it. Future studies will focus on the extent to which alterations in red cells of human diabetics can be used to predict the development of long-term sequelae of the disease.Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat

Effects of Allopurinol on Ketone Body Metabolism and Tissue Lipid Peroxidation in Alloxan Diabetes in Rats

The aim of the present study is to investigate whether or not xanthine oxidase (XO)–derived reactive oxygen species (ROS) may play a role in the pathogenesis of alloxan (ALX)–induced diabetes in rats using the specific XO inhibitor and hydroxyl radical scavenger, allopurinol&#x0D; The involvement of oxidative stress in ALX – diabetes was assessed by the measurement of plasma and various tissues lipid peroxides levels ( using thiobarbituric acid ( TBA ) reactive substances ). Furthermore, the ability of allopurinol to influence these and other biochemical parameters, including plasma and urine ketones levels were also investigated in diabetic rats.&#x0D; Rats were divided into four groups: control, untreated diabetic, allopurinol – treated diabetic, and insulin – treated diabetics. At the end of the one week experimental period, blood and tissue samples were obtained from anesthesized animals for the measurement of the above – mentioned parameters.&#x0D;    Although the single intraperitoneal (i.p.) injection of allopurinol (25 mg/kg body wt.) 1h before or 1h after ALX injection (100 mg/kg body wt., i.p.) failed to prevent the induction of diabetes, it did lower ketonuria and the incidence of early ketosis–associated mortality in diabetic animals in comparison with non–allopurinol–treated diabetic rats. Subsequent administration of allopurinol (25 mg/kg body wt., i.p.) every 48 hr for 1wk (i.e., 3 additional doses) also decreased plasma ketone bodies levels as well as plasma and tissue (heart, liver, kidney, pancreas) lipid peroxides levels in comparison with non–allopurinol–treated diabetic rats. Daily insulin injection (9–12 U/kg body wt., S.C.) for 1wk period normalized all of the above–mentioned abnormalities.&#x0D; The present results suggest that XO–derived ROS play a minor role (if any) in the diabetogenic effect of ALX. On the other hand, although the mechanism (s) underlying the protective effects of allopurinol on the diabetic state is presently unknown, these effects may reflect a possible association between impaired ketone body metabolism and lipid peroxidation: and suggest an effect of allopurinol on ketone body metabolism.</jats:p

Alterations in Free Radical Tissue-Defense Mechanisms in Streptozocin-Induced Diabetes in Rat: Effects of Insulin Treatment

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9–12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.</jats:p