Free Radical-mediated Oxidative Stress Research Articles

Assessment of antidiabetogenic potential of fermented soybean extracts in streptozotocin-induced diabetic rat

Most of the available drugs for the treatment of diabetes mellitus (DM) produce detrimental side effects, which has prompted an ongoing search for plant with the antidiabetic potential. The present study investigated the effect of soybean extracts fermented with Bacillus subtilis MORI, fermented soybean extracts (BTD-1) was investigated in streptozotocin (STZ)-induced diabetic rats. The possible effects of BTD-1 against hyperglycemia and free radical-mediated oxidative stress was investigated by assaying the plasma glucose level and the activity of enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). A significant increase in the levels of both plasma glucose and reactive oxygen species (ROS) was observed in the diabetic rats when compared to normal control group. After administration of BTD-1 (500 and 1000mg/kg/day), the elevated plasma glucose level was significantly reduced while the plasma insulin level and the activities of SOD, GSH-Px, CAT and MDA were significantly increased. The results suggest that administration of BTD-1 can inhibit hyperglycemia and free radical-mediated oxidative stress. The administration of BTD-1 also inhibited the contractile response by norepinephrine (10−10–10−5M) in the presence of endothelium, and caused significant relaxation by carbachol (10−8–10−5M) in rat aorta. These findings indicate that BTD-1 improves vascular functions on STZ-induced diabetic rats. Therefore, subchronic administration of BTD-1 could prevent the functional changes in vascular reactivity in STZ-induced diabetic rats. The collective findings support that administration of BTD-1 may prevent some diabetes-related changes in vascular reactivity directly and/or indirectly due to its hypoglycaemic effect and inhibition of production of ROS.

Abstract 3846: Vitamin D3 potentiates the antitumor effects of arsenic trioxide in human leukemia (HL-60) cells

Abstract Arsenic trioxide (ATO) is an innovative form of therapy that has recently been found to benefit acute promyelocytic leukemia (APL) patients. Our laboratory has demonstrated that ATO stimulates oxidative stress therefore causing ATO-induced cytotoxicity in human leukemia (HL-60) cells. Pro-oxidants have been known to play a role in free radical-mediated oxidative stress. Vitamin D3, an active metabolite of vitamin D, inhibits the growth of a number of cancer types such as prostate, breast, colorectal, leukemia, and skin cancers. The specific aim of this research was to determine whether co-exposure to vitamin D3 increases the efficacy of ATO through cytotoxicity, oxidative stress and apoptosis associated with increased ATO toxicity in human leukemia (HL-60) cells. In our current investigation, we performed the MTT assay and trypan blue exclusion test to measure cell viability. We also performed the lipid peroxidation assay to determine the levels of malondialdehyde (MDA) production in HL-60 cells co-exposed to ATO and vitamin D3 in combination. The results of trypan blue exclusion and MTT assay indicated that vitamin D3 exposure potentiates the toxic activity of ATO in HL-60 cells in a dose dependent manner. Co-administration of vitamin D3 and ATO resulted in a significant (P<0.05) increase in MDA level compared to ATO alone. A statistically significant and dose-dependent increase (p <0.05) was recorded in annexin V positive cells (apoptotic cells) with increasing doses of vitamin D3 in ATO-treated cells. This finding was confirmed by the result of DNA laddering assay showing clear evidence of DNA fragmentation in ATO and vitamin D3 treated HL-60 cells. Overall, the present study indicates that vitamin D3 potentiates the antitumor effects of ATO at least part, via cytotoxicity, oxidative stress, nucleosomal fragmentation and phosphatidylserine externalization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3846. doi:1538-7445.AM2012-3846

Micronutrients as therapeutic tools in the management of sickle cell disease, malaria and diabetes

The Global use of micronutrients in health care delivery has taken center stage due to the realization of their importance in disease management. Sickle cell disease, malaria and diabetes are among the diseases plaguing a good population of the developing world and the cost implication for their management is very high. Sickle cell disease and malari have anemia as a common factor and immunological disturbances are also prevalent in these disease conditions. Free radicals are generated in sickle cell disease, malaria and diabetes so a balance between minerals and antioxidants is imperative to maintain membrane integrity and function. Protection of red cell membranes from free radical-mediated oxidative stress is crucial to their management. Minerals such as copper, iron, chromium, magnesium, selenium and vanadium as well as vitamins like A, C, E, folate and the B group have been found to relieve oxidative stress associated with them. Micronutrients and their importance in the management of sickle cell disease, malaria and diabetes is reviewed here, with emphasis on the need to harness the natural resources abundant in our environment.

Antioxidant activity of methimazole–copper(II) bioactive species and spectroscopic investigations on the mechanism of its interaction with Bovine Serum Albumin

Free radical-mediated oxidative stress has been implicated in numerous autoimmune disorders including Graves’ disease. Hyperthyroidism results in a marked increase in intracellular antioxidant enzymes including superoxide dismutase. The later activity is significantly increased in untreated Graves’ patients while treatment with methimazole results in normalization of the free radical and antioxidant activity indices. In this context, and considering the findings mentioned above, the aim of the present study was to evaluate unknown biological activities of methimazole and its methimazole–copper(II) complex investigating their superoxide scavenger power. Under the applied experimental conditions, methimazole did not show superoxide dismutase (SOD) activity while the copper complexes exhibited a strong superoxide radical scavenging capacity. Bearing in mind that the capacity of drugs to bind and/or interact with albumin is essential for their pharmacokinetic and pharmacodynamic properties, a complete investigation of the binding ability of both compounds by using Fourier transform infrared (FT-IR), Raman and Fluorescence spectroscopies, and UV–Vis spectrophotometry was included. Besides, in order to probe the copper ligand environment the EPR spectra of such compounds were analyzed.

Evaluation of Oral Hygiene Status, Salivary Characteristics and Dental Caries Experience in Acute Lymphoblastic Leukemic (ALL) Children

Leukemia constitutes approximately 30% of all childhood cancers and Acute Lymphoblastic Leukemia (ALL) is the most common type of malignancy. Oral dryness, ulceration, increased dental decay seen is due to altered salivary flow rate and buffering capacity in these children. Oxidative stress may play an important role in the malignancies resulting in onset of inflammatory oral pathologies. Saliva constitutes first line of defense against free radical-mediated oxidative stress. The present study attempted to relate the oral health status, salivary flow rate, salivary pH, gingival health status, dental caries experience and total salivary antioxidant levels in ALL children. A total of 120 children aged 4-10 years (90 leukemic children, study group and 30 normal healthy siblings, control group) were divided into 4 groups of 30 each. Oral health status, gingival status and dental caries experience was recorded followed by un-stimulated saliva collection. Total antioxidant capacity of un-stimulated saliva was evaluated. The results depicted deterioration in oral health status, gingival status and increased dental caries experience in leukemic children. Salivary flow rate, salivary pH and total salivary antioxidant levels were lowered in leukemic children when compared with control group.

Effects of spinal or general anesthesia on F2-isoprostanes and isofurans during ischemia/reperfusion of the leg in patients undergoing knee replacement surgery

General and spinal anesthesia are used extensively in orthopedic surgery. However, these methods of anesthesia may result in different amounts of oxygen being delivered to the patient. Ischemia/reperfusion injury after release of the tourniquet initiates free radical-mediated oxidative stress. F2-isoprostanes are reliable markers of in vivo lipid peroxidation. However, under conditions of high oxygen tension, isofurans are formed. We aimed to compare plasma isofurans and F2-isoprostanes in spinal versus general anesthesia in patients undergoing knee-replacement surgery in a randomized, blinded study. Thirty-nine patients were randomized to spinal (SA; n=19) or general anesthesia (GA; n=20). Blood was collected before anesthesia, and a tourniquet was then applied to the limb during surgery. After release of the tourniquet, blood samples were collected at 30min, 2h, and 24h for measurement of plasma F2-isoprostanes and isofurans by gas chromatography–mass spectrometry. The two groups were comparable in age and body mass index. Plasma F2-isoprostanes were significantly lower in the GA patients compared with the SA patients (p=0.045). In contrast, the GA patients had significantly elevated plasma isofurans (p=0.032). Increased isofurans during GA compared with SA are likely to reflect increased oxidative stress due to elevated oxygen concentrations during GA. Further studies are required to assess the implications of these findings on perioperative outcomes.

Hesperidin Protects Renal and Hepatic Tissues Against Free Radical-Mediated Oxidative Stress During DMBA-Induced Experimental Breast Cancer

Hesperidin has been reported to have an excellent and wide variety of biological activities. This property has brought the compound to a new stage in the treatment of various oxidative stress-mediated diseases. The present investigation was aimed to evaluate the therapeutic potential of hesperidin by assaying the activities of antioxidant enzymes, lipid peroxidation, membrane bound marker enzymes, adenosine triphosphates, and TCA cycle enzymes, especially in kidney tissues during 7,12-dimethybenz(a)anthracene-induced breast cancer. Daily oral administration of hesperidin (30 mg/kg body wt) to breast cancer-bearing rats for 45 days demonstrated a significant (P < .05) decline in renal lipid peroxidation and membrane bound marker enzymes, as well as a remarkable increase in adenosine triphosphatases, mitochondrial functional enzymes, and renal antioxidants. Furthermore, histological studies of liver and kidney provided evidence of biochemical alterations. Thus, the protective effects of hesperidin on attenuating the peroxidation reaction and membrane bound marker enzyme activities as well as upregulation of adenosine triphosphatases, TCA cycle enzymes, and antioxidants suggest promising uses of flavonoglycoside hesperidin in the future treatment of oxidative stress-mediated diseases.

Protective effect of β-casomorphin-7 on type 1 diabetes rats induced with streptozotocin

The present study was aimed to investigate the possible effects of β-casomorphin-7, against hyperglycemia and free radical-mediated oxidative stress in streptozotocin-induced diabetic rats by assaying the blood glucose level and the activity of plasma enzymatic antioxidants, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px). A significant increase in the levels of both blood glucose and oxidative stress with a predominant decrease in antioxidant status was observed in the diabetic rats when compared to control rats. After 15 days oral administration of β-casomorphin-7 (7.5 × 10 −8mol/day), the elevated blood glucose level was reduced. Oral administration of β-CM-7 to diabetic rats showed an increase in the level of plasma insulin, the elevated plasma glucagon level was markedly reduced by the oral administration of β-CM-7. Oral administration of β-CM-7 to the diabetic group of rats also showed a significant elevation in the activity of SOD and catalase. Thus, the results of the present study suggest that β-casomorphin-7 can protect rats from hyperglycemia and free radical-mediated oxidative stress in diabetic rats.

Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats

Abstract Objectives To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Methods Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. Key findings The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Conclusions Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

Electron paramagnetic resonance spectroscopy in radiation research: Current status and perspectives

Exposure to radiation leads to a number of health-related malfunctions. Ionizing radiation is more harmful than non-ionizing radiation, as it causes both direct and indirect effects. Irradiation with ionizing radiation results in free radical-induced oxidative stress. Free radical-mediated oxidative stress has been implicated in a plethora of diseased states, including cancer, arthritis, aging, Parkinson's disease, and so on. Electron Paramagnetic Resonance (EPR) spectroscopy has various applications to measure free radicals, in radiation research. Free radicals disintegrate immediately in aqueous environment. Free radicals can be detected indirectly by the EPR spin trapping technique in which these forms stabilize the radical adduct and produce characteristic EPR spectra for specific radicals. Ionizing radiation-induced free radicals in calcified tissues, for example, teeth, bone, and fingernail, can be detected directly by EPR spectroscopy, due to their extended stability. Various applications of EPR in radiation research studies are discussed in this review.

Pancreatic tissue protective nature of D-Pinitol studied in streptozotocin-mediated oxidative stress in experimental diabetic rats

The present study was aimed to investigate the possible pancreatic tissue protective nature of D-Pinitol, a cyclitol present in soybean, against free radical-mediated oxidative stress in streptozotocin-induced diabetic rats by assaying the activity of pancreatic enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) and the levels of plasma non-enzymatic antioxidants such as vitamin E, vitamin C, ceruloplasmin and reduced glutathione (GSH). To assess the extent of oxidative stress, the levels of lipid peroxidation (LPO) and hydroperoxides in both plasma and pancreatic tissues were also measured. A significant increase in the levels of both lipid peroxides and hydroperoxides with a concomitant decrease in antioxidant status was observed in the diabetic rats when compared to control rats. Oral administration of D-Pinitol (50 mg/kg b.w./day for 30 days), a major cyclitol present in soybean, ameliorates the free radical-mediated alterations to near normalcy. The pancreatic tissue protective nature of D-Pinitol was further evidenced by histological observations. The results were statistically comparable with glyclazide, a standard hypoglycemic drug. Thus, the results of the present study suggest that D-Pinitol protects the pancreatic tissue from free radical-mediated oxidative stress in addition to its antidiabetic property.

Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats

To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

The effect of nebivolol treatment on oxidative stress and antioxidant status in patients with cardiac syndrome-X

Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several disorders. The aim of this study was to elucidate the effect of treatment with nebivolol on the metabolic state of oxidative stress, and antioxidant status markers in patients with cardiac syndrome-X (CSX), additionally, to compare with the effect of metoprolol treatment. Thirty patients, 17 female and 13 male, with CSX were enrolled in the study. Nebivolol (5 mg/day) or metoprolol (50 mg/day) was administrated for 12 weeks. Twelve hour fasting blood samples, taken at the initiation and on the third month of therapy, were analyzed for the levels of malondialdehyde (MDA), nitrite+nitrate (NOx), and the activity of myeloperoxidase (MPO), superoxide dismutase (SOD). No patient presented additional risk factors for increased reactive oxygen species levels. Compared with sixteen control participants, patients with CSX had significantly higher activity of MPO and levels of MDA, but significantly lower SOD activity and levels of NOx before treatment. After treatment, MPO activity and MDA levels were significantly reduced; SOD activity and NOx levels were significantly increased with nebivolol but remained unchanged with metoprolol. We have shown that patients with CSX who taken nebivolol have lower serum MPO activity, levels of MDA and higher serum SOD activity, NOx levels when compared with metoprolol treatment. Exercise stress test parameters were also ameliorated in patients who had taken nebivolol in contrast to metoprolol. Nebivolol treatment may be a novel treatment strategy in cases with CSX in the future.

Oxidative damage in brain from human mutant APP/PS-1 double knock-in mice as a function of age

Oxidative stress is strongly implicated in the progressive decline of cognition associated with aging and neurodegenerative disorders. In the brain, free radical-mediated oxidative stress plays a critical role in the age-related decline of cellular function as a result of the oxidation of proteins, lipids, and nucleic acids. A number of studies indicate that an increase in protein oxidation and lipid peroxidation is associated with age-related neurodegenerative diseases and cellular dysfunction observed in aging brains. Oxidative stress is one of the important factors contributing to Alzheimer’s disease (AD), one of whose major hallmarks includes brain depositions of amyloid beta-peptide (Aβ) derived from amyloid precursor protein (APP). Mutation in APP and PS-1 genes, which increases production of the highly amyloidogenic amyloid β-peptide (Aβ42), is the major cause of familial AD. In the present study, protein oxidation and lipid peroxidation in the brain from knock-in mice expressing human mutant APP and PS-1 were compared with brain from wild type, as a function of age. The results suggest that there is an increased oxidative stress in the brain of wild-type mice as a function of age. In APP/PS-1 mouse brain, there is a basal increase (at 1 month) in oxidative stress compared to the wild type (1 month), as measured by protein oxidation and lipid peroxidation. In addition, age-related elevation of oxidative damage was observed in APP/PS-1 mice brain compared to that of wild-type mice brain. These results are discussed with reference to the importance of Aβ42-associated oxidative stress in the pathogenesis of AD.

Age-Related Correlation Between Antioxidant Enzymes and DNA Damage With Smoking and Body Mass Index

To understand whether oxidants contribute to the initiation and/or promulgation toward aging, the present study has been undertaken on 220 healthy male volunteers aged 20-80 years selected from the defined electoral area (suburbs of Tirupati, Andhra Pradesh, India) to evaluate the concentrations of free radicals (superoxide anion, hydrogen peroxide), lymphocyte antioxidant enzymes (glutathione S-transferase, superoxide dismutase, catalase), and DNA damage in relation to obesity and smoking (lifestyles). A two fold increase of lymphocyte free radical generation (DNA damage) was observed in older age groups with a reduced antioxidant potential, forming a link between cigarette smoking and oxidative stress represented by an antioxidant imbalance. Body mass index had a positive relationship with oxidative stress, but antioxidant levels did not vary with body mass index. The findings conclude that free radical-mediated oxidative stress and DNA damage accelerate with lifestyle variations under reduced antioxidant potential.

The effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status

Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. Also, there is growing evidence supporting the role of reactive oxygen species in the pathogenesis of thyroid disorders. The aim of this study was to investigate the influence of hypothyroidism, hyperthyroidism, and their treatments on the metabolic state of oxidative stress, and antioxidant status markers. A total of 20 newly diagnosed patients with overt hypothyroidism due to Hashimoto's thyroiditis, 20 patients with overt hyperthyroidism due to Graves' disease, and 20 healthy subjects as the control group were enrolled in the study. Fasting blood samples (12 h), taken at the initiation, after the 30th and 60th day of therapy were analyzed for malondialdehyde, nitrite, vitamin E, vitamin A, beta-carotene, ascorbate, and myeloperoxidase and superoxide dismutase activity. No patient presented additional risk factors for increased reactive oxygen species levels. Malondialdehyde, nitrite, vitamin E, and myeloperoxidase activity increased in patients with hypothyroidism. After 2 months, the levels of nitrite and vitamin E were reduced to control levels by treatment. The patients with hyperthyroidism had increased levels of malondialdehyde and myeloperoxidase activity in comparison with the controls. Treatment with propylthiouracil attenuated these increments after 1 month. Our results reveal an increased generation of reactive oxygen species and impairment of the antioxidant system in patients with hyperthyroidism, and particularly in patients with hypothyroidism. These findings indicate that thyroid hormones have a strong impact on oxidative stress and the antioxidant system.

Antioxidant Effect ofHemidesmus indicuson Ethanol-Induced Hepatotoxicity in Rats

The antioxidant effect of the ethanolic root extract of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant used in soft drinks in India, was studied in rats with ethanol-induced hepatotoxicity. Administering 20% ethanol (5 g/kg of body weight/day) for 60 days to male Wistar rats resulted in significantly decreased body weight and increased liver/body weight ratio. The liver marker enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatae (ALP), gamma-glutamyl transpeptidase (GGT), and lactate dehydrogenase (LDH), were elevated. In addition, the levels of plasma, erythrocyte, and hepatic thiobarbituric acid-reactive substances (TBARS), hydroperoxides (LOOH), and conjugated dienes (CD) were also elevated in ethanol-fed rats as compared to those of the experimental control rats. Decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C, and alpha-tocopherol (vitamin E) were also observed in ethanol-administered as compared to control rats. Ethanolic root extract of H. indicus was administered at a dose of 500 mg/kg of body weight/day for the last 30 days of the experiment to rats with ethanol-induced liver injury, which significantly increased body weight, significantly decreased the liver/body weight ratio, AST, ALT, ALP, GGT, and LDH activities, and also the levels of TBARS, LOOH, and CD, significantly elevated the activities of SOD, CAT, GPx, and GSH in plasma, erythrocytes, and liver, and also increased levels of plasma and liver vitamin C and vitamin E at the end of the experimental period as compared to those of untreated ethanol-administered rats. Thus, our data indicate that treatment with H. indicus extract offers protection against free radical-mediated oxidative stress in plasma, erythrocytes, and liver of animals with ethanol-induced liver injury.

Reducing Iron Stores Lowers Cancer Risk in Patients with Peripheral Arterial Disease.

Background: Iron accumulation in excess of requirements has been implicated in risk of malignancy through increased iron-catalyzed free radical-mediated oxidative stress. Reduction of body iron stores may lower risk of cancer.Methods: A multi-center randomized, controlled, single-blinded clinical trial was conducted between May 1, 1999 and April 30, 2005 within the Department of Veterans Affairs Cooperative Studies Program; VA Cooperative Study #410. Its purpose was to test the hypothesis that reducing body iron stores by phlebotomy would influence all cause mortality (the primary endpoint) and combined death plus non-fatal myocardial infarction and stroke (the secondary endpoint) in a cohort of patients with symptomatic peripheral arterial disease. Patients with a diagnosis of visceral malignancy within the preceding five years were excluded. Patients were randomly assigned to control or reduction of iron stores by graded phlebotomy (avoiding iron deficiency) with stratification by hospital, age, entry ferritin, diagnosis of diabetes mellitus, smoking status and HDL/LDL ratio. Information on the occurrence of new visceral malignancies and cause-specific mortality including death due to cancer as collected prospectively.Results: This study enrolled 1,277 patients: 641 were randomized to control and 636 to iron reduction. Ferritin levels were reduced significantly in patients randomized to iron reduction. A new visceral malignancy was diagnosed during follow-up in 60 control and 38 iron reduction patients, a 37% decrease in risk with iron reduction (p = 0.023). Reduced risk was observed for several common tumor types. Iron reduction patients had lower cancer - specific mortality and lower all - cause mortality in patients diagnosed with cancer (p = 0.003 and 0.009, respectively) than control patients. Neither cancer risk nor mortality was affected by variables used to stratify the randomization or demographic variables at entry. Mean ferritin levels at entry were comparable for all patients that subsequently acquired versus did not acquire cancer (p = 0.314) and for patients randomized to either control or iron reduction that later acquired cancer (p = 0.927). Mean ferritin levels during follow-up in patients randomized to iron reduction that acquired cancer were comparable to levels in control patients (p=0.428) while follow-up ferritin levels were significantly lower in patients not acquiring cancer (p=0.017).Conclusions: Randomization to iron reduction was associated with a significantly lower cancer risk and mortality during follow-up. Patients randomized to iron reduction that acquired cancer were relatively non-compliant with intervention. These findings invite further study.

Impact of Hemidesmus indicus R.Br. extract on ethanol-mediated oxidative damage in rat kidney

The antioxidant effect of the ethanolic extract of Hemidesmus indicus R.Br. root (EHI), an indigenous Ayurvedic medicinal plant in India, was studied in rats with ethanol-induced nephrotoxicity. Administering 5 g/kg body weight/day of ethanol for 60 days to male Wistar rats resulted in significantly elevated levels of serum urea, creatinine and uric acid as well as kidney thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) as compared to those of the experimental control rats. Decreased levels of kidney superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E were also observed on alcohol administration as compared with those of the experimental control rats. EHI was administered at a dose of 500 mg/kg body weight/day for the last 30 days of the experiment to rats with ethanol-induced kidney injury, which significantly decreased the levels of serum urea, uric acid and creatinine as well as kidney TBARS, LOOH and CD and significantly elevated the activities of SOD, CAT, GPx, GSH, vitamin C and vitamin E in kidney as compared to that of untreated ethanol-administered rats. Histopathological observations also correlated with the biochemical parameters. Thus, the data indicate that treatment with EHI offers protection against free radical-mediated oxidative stress in kidney of animals with ethanol-induced nephtrotoxicity.

Radioprotective and Antioxidant Activity of Fractionated Extracts of Berries ofHippophae rhamnoides

Plants are an abundant source of medicinal compounds, some of which are useful in combating free radical-mediated oxidative stress. In the present study, initially two fractions designated REC-1001 (flavonoid-rich fraction) and REC-1002 (flavonoid-poor fraction) of Hippophae rhamnoides were screened on the basis of their reducing power in the aqueous phase. REC-1001 was selected for further study, since it exhibited 27.38 times higher antioxidant activity than REC-1002. REC-1001 also showed significant (P < .05) membrane protection potential at 50 microg/mL, which was attributed to its ability to scavenge peroxyl radicals (64.82 +/- 1.25% scavenging within 1,440 min). A significant (P < .05) difference of 67.02% in free radical scavenging activity at 1,000 ng/mL between REC-1001 and vitamin E demonstrated the extract fraction's worth in radiation protection. Such activities were attributed to the presence of quercetin, isorhamnetin, and kaempferol in this fraction. Further, REC-1001 was found to be nontoxic up to 200 mg/kg of body weight. This research suggests that the REC-1001 fraction of H. rhamnoides extract is a safe and effective antioxidant nutraceutical product.