Seizure prevention by the naturally occurring phenols,carvacrol and thymol in a partial seizure-psychomotor model

The natural compounds carvacrol and thymol completely prevented seizures in the 6 Hz, 32 mA partial seizure model. Carvacrol and thymol, both exhibited an ED₅₀ = 35.8 mg/kg, ip and yielded protective indices of 5.3 and 3.4, respectively. At 44 mA current intensity, carvacrol and thymol exhibited ED₅₀s of 88.82 mg/kg (PI = 2.15) and 73.0 mg/kg (PI = 1.65), respectively. Thymol, but not carvacrol showed partial inhibitory activity in the maximal electroshock (MES), sc Metrazol (scMET) and Corneal-kindled models. These results suggest that carvacrol and thymol are more efficacious anticonvulsants than suggested by their lower efficacies in the conventional MES and scMET tests.     

Evaluation of the effect of glucosamine on an experimental rat osteoarthritis model

AimsTo investigate the in vivo effect of glucosamine on articular cartilage in osteoarthritis (OA), we evaluated serum biomarkers such as CTX-II (type II collagen degradation) and CPII (type II collagen synthesis) as well as histopathological changes (Mankin score, toluidine blue staining of proteoglycans in an experimental OA model using rats.Main methodsOA was surgically induced in the knee joint by anterior cruciate ligament transection (ACLT) in rats. Animals were divided into three groups: sham-operated group (Sham), ACLT group without GlcN administration (? GlcN) and ACLT group with oral administration of glucosamine hydrochloride (+ GlcN; 1000 mg/kg/day for 56 days).Key findingsACLT induced macroscopic erosive changes on the surfaces of articular cartilage and histological damages such as increase of Mankin score. Of note, glucosamine administration substantially suppressed the macroscopic changes, although the effect on Mankin score was not significant. In addition, serum CTX-II levels were elevated in ?GlcN group compared to that in Sham group after the operation. Of importance, the increase of CTX-II was significantly suppressed by GlcN administration. Moreover, serum CP-II levels were substantially increased in + GlcN group compared to those in Sham and ? GlcN groups after the operation.SignificanceGlcN has a potential to exert a chondroprotective action on OA by inhibiting type II collagen degradation and enhancing type II collagen synthesis in the articular cartilage.     

HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: Potential role of the thiol antioxidant N-acetylcysteine amide

An increased risk of HIV-1 associated dementia (HAD) has been observed in patients abusing methamphetamine (METH). Since both HIV viral proteins (gp120, Tat) and METH induce oxidative stress, drug abusing patients are at a greater risk of oxidative stress-induced damage. The objective of this study was to determine if N-acetylcysteine amide (NACA) protects the blood brain barrier (BBB) from oxidative stress-induced damage in animals exposed to gp120, Tat and METH. To study this, CD-1 mice pre-treated with NACA/saline, received injections of gp120, Tat, gp120 + Tat or saline for 5 days, followed by three injections of METH/saline on the fifth day, and sacrificed 24 h after the final injection. Various oxidative stress parameters were measured, and animals treated with gp120 + Tat + Meth were found to be the most challenged group, as indicated by their GSH and MDA levels. Treatment with NACA significantly rescued the animals from oxidative stress. Further, NACA-treated animals had significantly higher expression of TJ proteins and BBB permeability as compared to the group treated with gp120 + Tat + METH alone, indicating that NACA can protect the BBB from oxidative stress-induced damage in gp120, Tat and METH exposed animals, and thus could be a viable therapeutic option for patients with HAD.     

Expression of BMP-receptor type 1A correlates with progress of osteoarthritis in human knee joints with focal cartilage lesions

Background aimsBone morphogenetic protein-2 (BMP-2) and its receptor type 1A (BMPR-1A) play significant roles in cartilage metabolism. The aim of this study was to evaluate a possible correlation between intra-articular expression of these proteins and the degree of osteoarthritis (OA) in human knees.MethodsBiopsies of synovia and debrided cartilage were taken in 15 patients undergoing autologous chondrocyte implantation. Expression of BMP-2 and BMPR-1A was evaluated semi-quantitatively by immunohistologic staining. These data were complemented by grading of cartilage lesions according to International Cartilage Repair Society (ICRS), defect size, duration of complaints, knee osteoarthritis scoring system (KOSS) and Henderson and Kellgren–Lawrence scores. General histologic stainings were used to determine Mankin, Pritzker and Krenn scores.ResultsThe expression of BMPR-1A but not of BMP-2 was significantly higher in cartilage biopsies taken in type 3 lesions with intact subchondral layer compared with type 4 defects (P < 0.05). In cartilage areas of bordering sectors, the intensity of immunohistologic staining of BMPR-1A was statistically significantly higher in mature cartilage compared with repair zones (P < 0.05). Expression of BMP-2 and its receptor 1A correlated in the cartilage biopsies (P < 0.02) but not in the synovia. The degree of OA was scored in all biopsies according to Mankin and Pritzker, and these scores correlated statistically significantly with BMPR-1A expression in the synovia (P < 0.05). In patients with an osteochondritis dissecans, the degree of OA was higher compared with other causes of chondromalacia, as evaluated by defect size, ICRS score, duration of complaints, Pritzker score and expression of BMPR-1A in cartilage (P < 0.05).ConclusionsThese data support the role of BMPR-1A as an indicator of OA progression in human knees with circumscribed cartilage lesions.     

Interlimb symmetry of dynamic knee joint stiffness and co-contraction is maintained in early stage knee osteoarthritis

Individuals with knee OA often exhibit greater co-contraction of antagonistic muscle groups surrounding the affected joint which may lead to increases in dynamic joint stiffness. These detrimental changes in the symptomatic limb may also exist in the contralateral limb, thus contributing to its risk of developing knee osteoarthritis. The purpose of this study is to investigate the interlimb symmetry of dynamic knee joint stiffness and muscular co-contraction in knee osteoarthritis.Muscular co-contraction and dynamic knee joint stiffness were assessed in 17 subjects with mild to moderate unilateral medial compartment knee osteoarthritis and 17 healthy control subjects while walking at a controlled speed (1.0 m/s). Paired and independent t-tests determined whether significant differences exist between groups (p < 0.05).There were no significant differences in dynamic joint stiffness or co-contraction between the OA symptomatic and OA contralateral group (p = 0.247, p = 0.874, respectively) or between the OA contralateral and healthy group (p = 0.635, p = 0.078, respectively). There was no significant difference in stiffness between the OA symptomatic and healthy group (p = 0.600); however, there was a slight trend toward enhanced co-contraction in the symptomatic knees compared to the healthy group (p = 0.051).Subjects with mild to moderate knee osteoarthritis maintain symmetric control strategies during gait.     

Anti-herpes virus activities of Achyranthes aspera: An Indian ethnomedicine,and its triterpene acid

The aim of this study was to evaluate the antiviral potential of methanolic extract (ME) of Achyranthes aspera, an Indian folk medicine and one of its pure compound oleanolic acid (OA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The ME possessed weak anti-herpes virus activity (EC₅₀ 64.4 μg/ml for HSV-1 and 72.8 μg/ml for HSV-2). While OA exhibited potent antiherpesvirus activity against both HSV-1 (EC₅₀ 6.8 μg/ml) and HSV-2 (EC₅₀ 7.8 μg/ml). The time response study revealed that the antiviral activity of ME and OA is highest at 2–6 h post infection. The infected and drug-treated peritoneal macrophage at specific time showed increased level of pro-inflammatory cytokines (IL6 and IL12). Further, the PCR of DNA from infected cultures treated with ME and OA, at various time intervals, failed to show amplification at 48–72 h, similar to that of HSV infected cells treated with acyclovir, indicating that the ME and OA probably inhibit the early stage of multiplication (post infection of 2–6 h). Thus, our study demonstrated that ME and OA have good anti-HSV activity, with SI values of 12, suggesting the potential use of this plant.     

Telomere susceptibility to cigarette smoke-induced oxidative damage and chromosomal instability of mouse embryos in vitro

Cigarette smoke is associated with high risk of lung, cardiovascular, and degenerative diseases, reduced fertility, and possibly the health of newborns. Cigarette smoke contains many components and exerts its genotoxicity in part by generating reactive oxidative stress. Telomeres consist of repeated ‘G’ rich sequences and associated proteins located at the chromosomal ends that maintain chromosomal integrity. We tested the hypothesis that telomere shortening and dysfunction are implicated in smoke associated oxidative damage and chromosomal instability using early mouse embryos in vitro and short-telomere mouse model. Mouse embryos exposed to smoke components, cigarette smoke condensate (CSC) at the concentration of 0.02 mg/ml continuously or 0.1 mg/ml for 20 h, or cadmium at 5-100 µM, exhibited increased oxidative stress and telomere shortening and loss, associated with chromosomal instability, apoptosis, and compromised embryo cleavage and development. Remarkably, reduction of oxidative stress by an antioxidant N-acetyl-L-cysteine (NAC) greatly reduced these toxicities. Notably, cadmium led to more severe oxidative damage and telomere dysfunction, which could be more effectively rescued by antioxidant treatment, than did CSC. Moreover, short telomeres predisposed embryos to smoke component-induced oxidative damage. These data further extend our understanding of mechanisms underlying smoke-induced oxidative damage to include telomere dysfunction and chromosomal instability.     

Mesenchymal stem cell-derived exosomes increase ATP levels,decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury

We have previously identified exosomes as the paracrine factor secreted by mesenchymal stem cells. Recently, we found that the key features of reperfusion injury, namely loss of ATP/NADH, increased oxidative stress and cell death were underpinned by proteomic deficiencies in ischemic/reperfused myocardium, and could be ameliorated by proteins in exosomes. To test this hypothesis in vivo, mice (C57Bl6/J) underwent 30 min ischemia, followed by reperfusion (I/R injury). Purified exosomes or saline was administered 5 min before reperfusion. Exosomes reduced infarct size by 45% compared to saline treatment. Langendorff experiments revealed that intact but not lysed exosomes enhanced viability of the ischemic/reperfused myocardium. Exosome treated animals exhibited significant preservation of left ventricular geometry and contractile performance during 28 days follow-up. Within an hour after reperfusion, exosome treatment increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β, and reduced phosphorylated-c-JNK in ischemic/reperfused hearts. Subsequently, both local and systemic inflammation were significantly reduced 24 h after reperfusion. In conclusion, our study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury. Hence, mesenchymal stem cell-derived exosomes are a potential adjuvant to reperfusion therapy for myocardial infarction.     

The effect of oxidative stress on nucleotide-excision repair in colon tissue of newborn piglets

Nucleotide-excision repair (NER) is important for the maintenance of genomic integrity and to prevent the onset of carcinogenesis. Oxidative stress was previously found to inhibit NER in vitro, and dietary antioxidants could thus protect DNA not only by reducing levels of oxidative DNA damage, but also by protecting NER against oxidative stress-induced inhibition. To obtain further insight in the relation between oxidative stress and NER activity in vivo, oxidative stress was induced in newborn piglets by means of intra-muscular injection of iron (200 mg) at day 3 after birth. Indeed, injection of iron significantly increased several markers of oxidative stress, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) levels in colon DNA and urinary excretion of 8-oxo-7,8-dihydroguanine (8-oxoGua). In parallel, the influence of maternal supplementation with an antioxidant-enriched diet was investigated in their offspring. Supplementation resulted in reduced iron concentrations in the colon (P = 0.004) at day 7 and a 40% reduction of 8-oxodG in colon DNA (P = 0.044) at day 14 after birth. NER capacity in animals that did not receive antioxidants was significantly reduced to 32% at day 7 compared with the initial NER capacity on day 1 after birth. This reduction in NER capacity was less pronounced in antioxidant-supplemented piglets (69%). Overall, these data indicate that NER can be reduced by oxidative stress in vivo, which can be compensated for by antioxidant supplementation.     

Oleanolic acid,a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet

Excess visceral adiposity may predispose to chronic diseases like hypertension and type 2 diabetes with a high risk for coronary artery disease. Adipose tissue secreted cytokines and oxidative stress play an important role in chronic disease progression. To combat adiposity, plant-derived triterpenes are currently receiving much attention as they possess antioxidant and anti-inflammatory properties and the ability to regulate glucose and lipid metabolism. In the search for potential antiobese compounds from natural sources, this study evaluated the effects of oleanolic acid (OA), a pentacyclic triterpene commonly present in fruits and vegetables, in glucose tolerance test and on high-fat diet (HFD)-induced obesity in mice. Adult male Swiss mice treated or not with OA (10 mg/kg) were fed a HFD during 15 weeks. Sibutramine (SIB) treated group (10 mg/kg) was included for comparison. Weekly body weights, food and water consumption were measured, and at the end of study period, the levels of blood glucose and lipids, plasma hormone levels of insulin, ghrelin and leptin, and the visceral abdominal fat content were analysed. Mice treated with OA and fed a HFD showed significantly (p < 0.05) improved glucose tolerance, decreased body weights, visceral adiposity, blood glucose, plasma lipids relative to their respective controls fed no OA. Additionally, OA treatment, while significantly elevating the plasma hormone level of leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than lipase. Sibutramine-treated group also manifested similar effects like OA except for blood glucose level that was not different from HFD control. These findings suggest that OA ameliorates visceral adiposity and improves glucose tolerance in mice and thus has an antiobese potential through modulation of carbohydrate and fat metabolism.     

Biomechanical characterisation of ovine spinal facet joint cartilage

The spinal facet joints are known to be an important component in the kinematics and the load transmission of the spine. The articular cartilage in the facet joint is prone to degenerative changes which lead to back pain and treatments for the condition have had limited long term success. There is currently a lack of information on the basic biomechanical properties of the facet joint cartilage which is needed to develop tissue substitution or regenerative interventions. In the present study, the thickness and biphasic properties of ovine facet cartilage were determined using a combination of indentation tests and computational modelling. The equilibrium biphasic Young's modulus and permeability were derived to be 0.76±0.35 MPa and 1.61±1.10×10^?15 m⁴/(Ns) respectively, which were within the range of cartilage properties characterised from the human synovial joints. The average thickness of the ovine facet cartilage was 0.52±0.10 mm, which was measured using a needle indentation test. These properties could potentially be used for the development of substitution or tissue engineering interventions and for computational modelling of the facet joint. Furthermore, the developed method to characterise the facet cartilage could be used for other animals or human donors.     

Pharmacological treatment with diacerein combined with mechanical stimulation affects the expression of growth factors in human chondrocytes

BackgroundOsteoarthritis (OA) as the main chronic joint disease arises from a disturbed balance between anabolic and catabolic processes leading to destructions of articular cartilage of the joints. While mechanical stress can be disastrous for the metabolism of chondrocytes, mechanical stimulation at the physiological level is known to improve cell function. The disease modifying OA drug (DMOAD) diacerein functions as a slowly-acting drug in OA by exhibiting anti-inflammatory, anti-catabolic, and pro-anabolic properties on cartilage. Combining these two treatment options revealed positive effects on OA-chondrocytes.MethodsCells were grown on flexible silicone membranes and mechanically stimulated by cyclic tensile loading. After seven days in the presence or absence of diacerein, inflammation markers and growth factors were analyzed using quantitative real-time PCR and enzyme linked immune assays. The influence of conditioned medium was tested on cell proliferation and cell migration.ResultsTensile strain and diacerein treatment reduced interleukin-6 (IL-6) expression, whereas cyclooxygenase-2 (COX2) expression was increased only by mechanical stimulation. The basic fibroblast growth factor (bFGF) was down regulated by the combined treatment modalities, whereas prostaglandin E2 (PGE2) synthesis was reduced only under OA conditions. The expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor A (VEGF-A) was down-regulated by both.ConclusionsFrom our study we conclude that moderate mechanical stimulation appears beneficial for the fate of the cell and improves the pharmacological effect of diacerein based on cross-talks between different initiated pathways.General significanceCombining two different treatment options broadens the perspective to treat OA and improves chondrocytes metabolism.     

Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: Implications in Huntington's disease

The study was designed to investigate the beneficial effect of quercetin supplementation in 3-nitropropionic acid (3-NP) induced model of Huntington's disease (HD). HD was induced in rats by administering sub-chronic dose of 3-NP, intraperitoneally, twice daily for 17 days. Quercetin was supplemented at a dose of 25 mg/kg body weight by oral gavage for 21 days. At the end of treatment, mitochondrial bioenergetics, mitochondrial swelling, oxidative stress, neurobehavioral deficits and histopathological changes were analyzed. Quercetin supplementation was able to reverse 3-NP induced inhibition of respiratory chain complexes, restore ATP levels, attenuate mitochondrial oxidative stress in terms of lipid peroxidation and prevent mitochondrial swelling. Quercetin administration also restored the activities of superoxide dismutase and catalase along with thiol content in 3-NP treated animals. Beneficial effect of quercetin administration was observed on 3-NP induced motor deficits analyzed by narrow beam walk and footprint analysis. Histopathological analysis of 3-NP treated rats revealed pyknotic nuclei and astrogliosis in striatum, which were reduced or absent in quercetin supplemented animals. Altogether, our results show that quercetin supplementation to 3-NP induced HD animals ameliorated mitochondrial dysfunctions, oxidative stress and neurobehavioral deficits in rats showing potential of this flavonoid in maintaining mitochondrial functions, suggesting a putative role of quercetin in HD management.     

The binding of okadaic acid analogs to recombinant OABP2.1 originally isolated from the marine sponge Halichondria okadai

The binding between [24-³H]okadaic acid (OA) and a recombinant OA binding protein OABP2.1 was examined using various OA analog, including methyl okadaate, norokadanone, 7-deoxy OA, and 14,15-dihydro OA, 7-O-palmitoyl DTX1, to investigate the structure activity relationship. Among them, 7-O-palmitoyl DTX1, which is one of the diarrhetic shellfish poisoning (DSP) toxins identified in shellfish, displayed an IC₅₀ for [24-³H]OA binding at 51 ± 6.3 nM (Mean ± SD). In addition, a synthetic compound, N-pyrenylmethyl okadamide, exhibited its IC₅₀ at 10 ± 2.9 nM (Mean ± SD). These results suggested that the recombinant OABP2.1 and the N-pyrenylmethyl okadamide might be core substances in a novel assay for the DSP toxins.     

Energy budget,oxidative stress and antioxidant in striped hamster acclimated to moderate cold and warm temperatures

The mechanism of the rate of living-free radical theory suggests that higher rate of oxidative metabolism results from greater rate of mitochondria oxidative phosphorylation, leading to a consequent increase in production of free radicals. However, the relation between metabolic rate and oxidative stress is tissue dependent in animals acclimated to cold temperatures. Here we examined oxidative stress, reflected by changes of antioxidant activity and other related markers, in striped hamsters acclimated to moderate cold (15 °C), room (23 °C) or warm temperature (30 °C) for 6 weeks, by which either higher or lower metabolic rate was induced experimentally. Energy intake and the rate of metabolism and nonshivering thermogenesis were increased at 15 °C, but decreased at 30 °C compared with that at 23 °C. Effects of temperatures on the markers of both oxidative stress and antioxidant activities were rarely significant. The percentages of positive correlation between the 11 tissues (brain, BAT, liver, heart, lung, kidneys, stomach, small and large intestine, caecum and skeletal muscle) were 14.5% (8/55) for catalase (CAT), 7.3% (4/55) for the capacity of inhibition of hydroxyl free radical (CIH), 5.5% (3/55) for activities of superoxide dismutase (SOD), 1.8% (1/55) for total antioxidant capacity (T-AOC), 4.3% (2/46) for H₂O₂ and 11.1% (4/36) for the capacity of inhibition of hydroxyl free radical (CIH). This indicated that the tissue-dependent changes of both oxidative stress and antioxidant activity were less consistent among the different tissues. Finally the data from this study were less consistent with the prediction of the mechanism of the rate of living-free radical theory.     

Comparative analysis of conventional and biological treatment in healing of bone disease

The healing of Bone tissue consists of a complex process. Hence, we designed our study to evaluate chondrial diseases, which are as they have a very low healing capacity. Seventy two elderly osteoarthritis (OA) and 54-paediatric juvenile idiopathic arthritis (JIA) patients were included. The group was divided as 24 OA patients and 18 JIA patients in each group. Group I received Hyualuronic acid and glucocorticoides. Group II received platelet rich plasma and fibrin glue. Group III received PRP, fibrin glue, and MSC. 40 control patients received only PRP treatment. Out of 72 OA patients 35 (48.6%) male and 37 (51.4%) female with mean age of 48 ± 6.5 years. 64 (88.9%) Patients had pain and swelling. 52 (72.2%) lacked flexibility. 42 (58.3%) had hypertrophy. 28 (38.9%) had less cartilage thickness. 34 (47.2%) were in grade 3, grade 2 has 28 (38.9%) and grade 1 has 10 (13.9%) patients respectively. Among 54 JIA patients 28 (51.9%) male and 26 (48.1%) female patients with mean, age 4.6 ± 3.8 years. 39 (72.2%) had pain and swelling. 32 (59.3%) lacked flexibility. 29 (53.7%) children’s had functional disability. Group I patients showed 30% improvement with no statistical significance (P < 0.21). Group II showed 45% improvement with statistical significance (P < 0.01). In Group III 80%, improvement was observed with statistical significance (P < 0.001). In 40 control patients, 60% improvement was observed. In conclusion, use of these MSC, PRP, and PPP are safe and less cost effective for treating OA and JIA.     

Hyperosmolaric contrast agents in cartilage tomography may expose cartilage to overload-induced cell death

In clinical arthrographic examination, strong hypertonic contrast agents are injected directly into the joint space. This may reduce the stiffness of articular cartilage, which is further hypothesized to lead to overload-induced cell death. We investigated the cell death in articular cartilage while the tissue was compressed in situ in physiological saline solution and in full strength hypertonic X-ray contrast agent Hexabrix^TM. Samples were prepared from bovine patellae and stored in Dulbecco’s Modified Eagle’s Medium overnight. Further, impact tests with or without creep were conducted for the samples with contact stresses and creep times changing from 1 MPa to 10 MPa and from 0 min to 15 min, respectively. Finally, depth-dependent cell viability was assessed with a confocal microscope. In order to characterize changes in the biomechanical properties of cartilage as a result of the use of Hexabrix?, stress-relaxation tests were conducted for the samples immersed in Hexabrix? and phosphate buffered saline (PBS). Both dynamic and equilibrium modulus of the samples immersed in Hexabrix? were significantly (p<0.05) lower than those of the samples immersed in PBS. Cartilage samples immersed in physiological saline solution showed load-induced cell death primarily in the superficial and middle zones. However, under high 8–10 MPa contact stresses, the samples immersed in full strength Hexabrix? showed significantly (p<0.05) higher number of dead cells than the samples compressed in physiological saline, especially in the deep zone of cartilage. In conclusion, excessive loading stresses followed by tissue creep might increase the risk for chondrocyte death in articular cartilage when immersed in hypertonic X-ray contrast agent, especially in the deep zone of cartilage.     

Purple carrot extract protects against cadmium intoxication in multiple organs of rats: Genotoxicity,oxidative stress and tissue morphology analyses

The aim of this study was to investigate if purple carrot extract is able to protect against the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis, genotoxicity and oxidative status were investigated in this setting. A total of twenty Wistar rats weighing 250 g on the average, and 8 weeks age were distributed into four groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and Purple carrot extract groups at 400 mg/L or 800 mg/L. Histopathological analysis revealed that liver from animals treated with purple carrot extract improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as depicted by comet and micronucleus assays in animals treated with purple carrot extract. SOD-CuZn and cytocrome C gene expression increased in groups treated with purple carrot extract. Purple carrot extract also reduced the 8OHdG levels in liver cells when compared to cadmium group. Taken together, our results demonstrate that purple carrot extract is able to protect against cadmium intoxication by means of reducing tissue regeneration, genotoxicity and oxidative stress in multiple organs of Wistar rats.     

Trace elements,oxidative stress and glycemic control in young people with type 1 diabetes mellitus

Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA_1C < 9.0%) and 40 patients with poor glycemic control (HbA_1C ≥ 9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA_1C ≥ 9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p < 0.001) and the levels of urinary 8-OHdG (p = 0.007) and HbA_1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.