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1.
Oxidative stress conditions associated with atherosclerosis leads to oxidative modification of low-density lipoprotein (LDL). The body’s capabilities to inhibit LDL oxidation and to remove or neutralize the atherogenic oxidized LDL (ox-LDL) are limited. When the LDL cholesterol level increases in the blood, it leads to dangerous consequences like atherosclerosis, leading to myocardial infarction. The major effect of an antioxidant in the LDL environment is to prevent the formation of ox-LDL (during atherogenesis. Strategies to reduce LDL oxidation and prevent atherogenesis can involve the enrichment of arterial cells with potent antioxidants that can prevent oxidative damage to the arterial wall. The objective of this study is to evaluate the effect of l-arginine on serum lipid and cholesterol levels in the patients of acute myocardial infarction (AMI). The study consisted of 70 AMI patients and 60 healthy individuals (serving as control) age 55–65 years. Serum levels of total cholesterol, high density lipoprotein (HDL), LDL and Triglycerides were determined on day 1 and day 15 of l-arginine administration (oral dose 3 g/day). The total cholesterol/HDL and the LDL/HDL ratio were calculated and compared. As per the observations, l-arginine administration was found to improve the lipid profile of the subjects. Hence it could be used as an adjuvant therapy for AMI and as a preventive measure for the onset of the disease in the healthy elderly also.  相似文献   

2.
The study was designed to evaluate the antioxidant activity and effect of Cymbopogon martinii (Roxb.) Wats. (Poaceae) leaves on the activity of monoamine oxidase and kinetics of enzyme inhibition. Ethanol extract of C. martinii and rat brain mitochondrial monoamine oxidase preparation ware used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver–Burk plot. The DPPH was used as a source of free radical to evaluate antioxidant potential. It is observed that, the ethanolic extract of C. martinii inhibits the monoamine oxidase activity with competitive mode of inhibition. The V max (0.01 mM/min) remained constant while, K m varied from 21.00 ± 1.1, 43.33 ± 1.5 and 83.33 ± 1.4 mM for 100–500 μg/ml concentration of C. martinii. The K i values were calculated to be 90.00 ± 0.87, 75.00 ± 0.69, 68.18 ± 0.68 μg for 100–500 μg/ml concentration of C. martini. It also shows a significant DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging (IC50 = 0.34 ± 0.05 mg/ml) and reducing activity (IC50 = 0.70 ± 0.22 mg/ml). The C. martini can be considered as a possible source of MAO inhibitor used in the treatment of depression and other neurological disorders.  相似文献   

3.
The present study was conducted to investigate the oxidant–antioxidant status in iron deficient pregnant anemic women. One hundred thirty pregnant women with iron deficiency anemia (IDA) were divided into three groups, namely mild (50), moderate (50) and severe (30) anemic along with pregnant healthy women as controls (50). The complete blood count, plasma lipid peroxidation products, enzymatic and non-enzymatic antioxidants were measured according to respective protocols. The levels of complete blood count, iron, ferritin along with antioxidant enzymes namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly reduced in all IDA groups. However, the level of oxidized glutathione, lipid peroxides, protein carbonyls, conjugated dienes were found significantly increased in all anemic patients. Antioxidant vitamins, namely C, E and A were also found significantly decreased in IDA patients. On the basis of our results, it may be concluded that IDA tends to increase the pro-oxidant components, which may result in various complications including peroxidation of vital body molecules resulting in increased risk for pregnant women as well as fetus.  相似文献   

4.
Nitric oxide (NO) a free radical having both cytoprotective as well as tumor promoting agent is formed from l-arginine by converting it to l-citrulline via nitric oxide synthase enzymes. The reaction product of nitric oxide with superoxide generates potent oxidizing agent, peroxynitrite which is the main mediator of tissue and cellular injury. Peroxynitrite is reactive towards many biomolecules which includes amino acids, nucleic acid bases; metal containing compounds, etc. NO metabolites may play a key role in mediating many of the genotoxic/carcinogenic effects as DNA damage, protein or lipid modification, etc. The basic reactions of nitric oxide can be divided as direct effect of the radical where it alone plays a role in either damaging or protecting the cell milieu and an indirect effect in which the byproducts of nitric oxide formed by convergence of two independent radical generating pathways play the role in biological reactions which mainly involve oxidative and nitrosative stress. Nitric oxide is also capable of directly interacting with mitochondria through inhibition of respiration or by permeability transition. Reaction of nitric oxide with metal ions include its direct interaction with the metals or with oxo complexes thereby reducing them to lower valent state. Excessive production of nitric oxide can be studied by inhibiting the synthetic pathway of nitric oxide using both selective or specific nitric oxide synthase inhibitor or non-selective nitric oxide synthase inhibitor with respect to isoforms of nitric oxide.  相似文献   

5.
GARS–AIRS–GART is crucial in studies of Down syndrome (DS)-related mental retardation due to its chromosomal location (21q22.1), involvement in de novo purine biosynthesis and over-expression in fetal DS brain postmortem samples. GARS–AIRS–GART regions important for structure–function were screened for mutations that might alter protein levels in DS patients. Mutation screening relied on multiplex/singleplex PCR-based amplification of genomic targets followed by amplicon size determination/fingerprinting. Serum protein samples were resolved by SDS-PAGE and immunoblotted with a GARS–AIRS–GART monoclonal antibody. No variation in amplicon size/fingerprints was observed in regions encoding the ATP-binding, active site residues of GARS, the structurally important glycine-rich loops of AIRS, substrate-binding, flexible and folate-binding loops of GART or the poly-adenylation signal sequences. The de novo occurrence or inheritance of large insertion/deletion/rearrangement-type mutations is therefore excluded. Immunoblots show presence of GARS–AIRS–GART protein in all patient samples, with no change in expression levels with respect to either sex or developmental age.  相似文献   

6.
The purpose of this study is optimizing the l-arginine (l-Arg) doses on the basis of chemical structure in regional accessible tumor therapy to settle down a new protocol for the treatment of cancer. 3H-thymidine-based cell proliferation assay was performed in vitro on tumor cell lines of fibrosarcoma (FS), lymphosarcoma-ascitic and on normal cell line of NIH 3T3 after treatment with different concentrations of l-Arg in phosphate buffered saline (PBS). The cultures were harvested after 22 h and the incorporated radioactivity was counted to identify their histologic grades as described in earlier studies. In vivo therapy of murine tumors was conducted where FS cells injected subcutaneously at ventro-lateral position of mice. Various drug delivery schedules were injected into the centre of tumor base, once a day for 4 days. Tumor diameter and survivals were monitored where the day of sacrifice was considered for monitoring the survival period. By identifying the histologic grades of the treated cultures in vitro and in vivo by different concentrations of l-Arg, the corresponding energy of such concentrations were determined. An efficient model with a good fit (R2 = 0.98) was established to describe the energy yield by l-Arg dose. The equivalence between the tumor histologic grade and energy of the l-Arg dose delivered in saline (PBS) environment is the optimum condition for regional tumor therapy achieves higher survival rate. The selective cytotoxicity to tumor cells with minimal damage to normal cells by l-Arg due to its chemical structure suggests to be considered the most promising drug for regional therapy of the accessible tumors like breast cancers of early stage with no distant metastasis.  相似文献   

7.
Objective of this study was to obtain a better understanding of the mechanism responsible for the d-galactosamine (d-GalN) induced hepatotoxicity and to study the effect of catechin against d-GalN induced hepatotoxicity. Catechin 50 and 100 mg/kg b.wt was administered for 1 week by oral route. Liver damage was induced by intra-peritoneal administration of 400 mg/kg b.wt d-galactosamine on the last day of catechin treatment. At the end of treatment all animals were killed and liver enzyme levels were estimated. Dissected hepatic samples were used for histopathology, RNA isolation, expression studies of Bax, Bcl-2 and p53 mRNA levels and mitochondrial membrane potential studies. We found that increases in the liver enzyme activity and decrease in antioxidant enzyme activity by d-GalN were significantly restricted by oral pretreatment with catechin. Disruption of mitochondrial membrane potential, up regulation of p53, Bax and down regulation of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively prevented by pretreatment with catechin.  相似文献   

8.
Guggulsterone, a mixture of cis (E) and trans (Z) isomers (7∶3 w/w) was synthesized from 16-DPA. The isomers were separated by column chromatography and evaluated for cardioprotective and antioxidant activities. Myocardial necrosis induced by isoproterenol in rats caused marked increase in serum creatine phosphokinase and glutamate pyruvate transaminase. Simultaneously in ischemic heart, phospholipase, xanthine oxidase and lipid peroxides were enhanced following depletion of glycogen, phospholipids and cholesterol. Treatment with guggulsterone and its both isomers at the dose of 50 mg/kg po., significantly protected cardiac damage as assessed by the reversal of blood and heart biochemical parameters in ischemic rats. The cardioprotective activity of guggulsterone and of both the isomers were compared with that of gemfibrozil at the same doses. Guggulsterone and both the isomers at tested concentrations (5–20mM) inhibited oxidative degradation of lipids in human low-density lipoprotein and rat liver microsomes induced by metal ionsin vitro. The drug counteracted against the generation of superoxide anions (O2) and hydroxyl radicals (OH−) in non-enzymic test systems. It is suggested that cardioprotective and antioxidant activities of synthetic guggulsterone and guggulsterone obtained from gum resinCommiphora mukul that contains isomers E & Z in the ratio of 46∶54w/w are the same.  相似文献   

9.
Leptin, a 16 kDa nonglycosylated hormone, is produced by mature adipocytes and functions primarily in the hypothalamus to reduce food intake and body weight. To explore a new approach for high-level expression of human Leptin in Escherichia coli, the human Leptin gene, synthesized according to the published sequence, was cloned into the vector pET32a to construct a fusion expression plasmid: Trx–Leptin/pET32a. Our data showed that more than 40% of the fusion protein Trx–Leptin was expressed in soluble form. After purified by Ni-IDA affinity chromatography, cleaved by enterokinase and applied Ni-IDA affinity chromatography again, purified Leptin with homogeneity over 96% was achieved. The bio-functional experiments of purified Leptin showed a significant reduction in food intake and body weight of female mice treated with Leptin by comparing with control mice, and it indicated that the purified Leptin has full biological activity. In addition, our expression system was a very low-cost and efficient prokaryotic expression system. So taken together, our results demonstrated that our expression system of bio-active Leptin provided a new method for producing Leptin in big scale and would be widely applied in commercial Leptin producing industries.  相似文献   

10.
Multiple mechanisms underlie the human aging process, but interest continues in the role that free radicals and antioxidants may play. The concentrations of lymphocyte free radical generation (O2 −& H2O2), DNA damage and antioxidant enzyme levels (glutathione Stransferase, superoxide dismutase and catalase) were evaluated in 110 healthy individuals with an age range of 20–80 years. The antioxidant enzyme levels were significantly less in very old age when compared to young. Moreover, the levels of free radical concentration and DNA damage were increased in the same age group with respect to younger group. Cigarette smoking had a positive relation with free radicals and DNA damage, and inverse relation with antioxidants. On the other hand, body mass was found to have positive relation with free radical generation only. The data indicate that depletion of antioxidant enzyme levels would render the older people more susceptible to free radical stress and DNA damage.  相似文献   

11.
Graves’ disease (GD) is an organ-specific heterogenous autoimmune disorder associated with T-lymphocyte abnormality affecting the thyroid, eyes and skin. GD is a multifactorial disease that develops as a result of complex interaction between genetic susceptibility genes and environmental factors. It has been suggested that the Cytotoxic T lymphocytes associated molecule-4 (CTLA-4) is a genetic susceptibility candidate for GD. The present study was focused on A/G polymorphism at position 49 in exon-1 of the CTLA-4 gene in 80 GD patients (GP) and 80 sex and age matched healthy individuals among South Indian (Madurai) population. Serum concentrations of thyroid hormone (T4, T3 and TSH) were determined by using automated analyzer. The genomic DNA was isolated from the patient and control groups and genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis using Bbv1. Significant difference (P < 0.001) was observed in the level of T3, T4 and TSH in GD patients and healthy individuals. The results revealed the CTLA-4 gene G/G genotype to be 32 (40%) in patients and 26 (32.50%) in healthy individuals, A/G genotype to be 37 (46.25%) in patients and 25 (31.25%) in healthy individuals and A/A genotype to be 11 (13.75%) in patients and 29 (36.25%) in healthy individuals. The calculated odds ratio (OR) in individuals with mutant genotype (GG/AG) reveal 3.6 fold risk for GD (95% confidence interval = 1.6–7.8). The mutant “G” allele frequency was observed to be 0.63 in GD patients and 0.48 in healthy individuals. Thus the present study demonstrates an association between the CTLA-4 gene polymorphism and Graves’ disease.  相似文献   

12.
This review article on the beneficial uses of Allium antioxidants tries to give some answers to the recent doubts raised by Singh et al. (Ind J Clin Biochem 25(3):225–243, 2010) against the claim of some researchers that Antioxidants (AOs) are miraculous molecules. Many people still believe that vitamins like A, C and E are the only true AOs that play important role in the corrections of metabolic derangements in life style diseases and hence all their faults are attributed to the failures of AOs as a class. This is quite unfair as there are many other natural AOs that do equal or even better AO action than the vitamins. Such is the case with the Allium S-alkyl sulfoxide aminoacids and their breakdown products viz, the various poly sulfides and their oxides e.g. allicin and ajoene type compounds which trap electrons mainly. It is true that antioxidant vitamins and β-carotene a precursor of Vitamin A bring about problems as prooxidant or as agents that block some metabolic pathways and gene expression. Again the argument that AOs cannot improve the level of antioxidant enzymes like SOD, catalase and glutathione Px is also not universal. Actually allium AOs can even spare the use of antioxidant vitamins in the body and enhance the action of antioxidant enzymes and supply of ATP and other nutrients to the tissues as the former are good vasodialators and promoters of membrane permeability. The use of AOs should be selective and moderate. Allium AOs satisfy the role of ideal AOs based on many of their invivo and invitro actions reported by the author and others. Their metabolits can regenerate them and recycle them for a sufficient time in the body. They have non antioxidant effects also such as antiplatelet, fibrinolytic, antiinflammatory, immunomodulatory, antiageing actions etc. Plant derived AOs may be more beneficial and better tolerated in their partially purified forms rather than in their absolutely purified forms as the accompanying principles have some protective and regulatory effects in general. This and other aspects of allium AOs are discussed in the paper.  相似文献   

13.
Terminalia arjuna (T. arjuna) stem bark was successively extracted with petroleum ether (A), solvent ether (B), ethanol (C) and water (D). The lipid lowering activity of these four fractions A, B, C, and D was evaluatedin vivo in two models viz., triton WR-1339 induced hyperlipemia in rats as well as fructose rich high fat diet (HFD) fed diabetic- dyslipidemic hamsters. Hyperlipidemia induced by triton caused marked increase in the plasma levels of total cholesterol (Tc), triglyceride (Tg) and phospholipids (PL) in rats. After treament withT. arjuna fractions A, B, C, and D at the doses of 250 mg/kg per oral (p.o.),only the ethanolic fraction (C) exerted significant lipid lowering effect as assessed by reversal of plasma levels of Tc, Tg and PL in hyperlipidemic rats. In another experiment, feeding with HFD produced marked dyslipidemia as observed by increased levels of plasma Tc, Tg, glucose (Glu), glycerol (Gly) and free fatty acids (FFA) in hamsters. After treatment withT. arjuna fractions at the doses of 250 mg/kg p.o. only two fraction (B and C) could exert significant lowering in the plasma levels of lipids and Glu. in dyslipidemic hamsters.In vitro experimentT. arjuna fractions at tested concentrations (50–500 μg/ml) inhibited the oxidative degradation of lipids in human low density lipoprotein and rat liver microsomes induced by metal ions. These fractions when tested against generation of oxygen free radicals at the concentrations (50–500 μg/ml), counteracted the formation of superoxide anions (O−2) and hydrodyl radicals (OH) in non enzymic test systems. The efficacy ofT. arjuna fractions as antidyslipidemic and antioxidant agents was found, fraction C> fraction B> fraction A.  相似文献   

14.
Lactate dehydrogenase (LDH) and its isoenzyme profile, Nacety-β-d-glucosaminidase (NAG) and alanine aminopeptidase (AAP) enzyme activities were measured in 21 cases with well documented acute untreated urinary tract infections (UTI) and compared with a group of 68 normal healthy subjects matched for age and sex. Urinary NAG, AAP and LDH total activities were highly elevated (3–30 fold for NAG, 2–10 fold for AAP and 2–50 fold for LDH over upper limit of normal) in upper tract infections. In lower tract infections there was a marginal elevation in NAG and LDH while AAP activity was very high; though there was no overlap. Further, the isoenzyme profile of LDH showed predominance of LD-5 isoenzyme in all cases of pyelonephritis, while it was completely absent in all the cases of lower tract infections. We conclude that urinary NAG and LDH-5 isoenzyme would serve as specific non-invasive parameters for differential localization of urinary tract infections.  相似文献   

15.
There is scanty information on the role of genetic factors, especially those relating to haptoglobin (Hp) phenotypes in the expression of complications among diabetes mellitus patients in Ghana. In this study, we investigated whether there is any association between Hp phenotypes and diabetic complications and to determine if association of the Hp phenotypes with diabetic complications in Ghanaian diabetics differ from those in Caucasians. A total of 398 participants were randomly recruited into the study. These comprised diabetic patients numbering 290 attending a diabetes Clinic in Ghana and 108 non-diabetic controls from the same community. Analyses of the results indicate that most of the diabetics with complications were of the Hp 2–2 (35%) and Hp 2–1 (23.9%) phenotypes. Fewer diabetics were found to be of the Hp 2–1 M phenotype. The controls were mostly of Hp 1–1 and Hp 2–1 M phenotypes. The odds ratio of having complications in a diabetic with an Hp 2–2 phenotype was 18.27 times greater than that for Hp 0–0. Hp 2–2 phenotype with its poor antioxidant activity may therefore be a useful predictor for the propensity of an individual to develop diabetes complications.  相似文献   

16.
WHO-Tropical Disease Research scheme highlighted the need for development of new anti-filarial drugs. Certain antibiotics have recently been found effective against Wolbachia, co-existing symbiotically with filarial parasites. Inflammatory response entails oxidative mechanism to educe direct anti-microbial effect. In the present study microfilariae were maintained in vitro in medium supplemented with varying concentrations of tetracycline, doxycycline (20–100 μg/ml) or ciprofloxacin (50–250 μg/ml) separately to find out any involvement of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of motility of the microfilariae was measured after 48 h and correlated with the levels of MDA, nitric oxide and protein-carbonylation. Significant loss of microfilarial motility was recorded with increasing concentration of tetracycline and doxycycline but with ciprofloxacin the effect was not marked. Agents with high antifilarial activity revealed significant association with oxidative parameters in a dose dependent manner. The result suggests that oxidative effect might be exploited to design novel antifilarial drug candidate.  相似文献   

17.
Vitamin B12 being water soluble is excreted in the urine when administered in excess. The probability of finding an abnormally excess serum concentration would be almost surreal. We report a peculiar clinical situation that may impact the vitamin B12 immunoassay on the Roche Elecsys 2010 due to excess analyte concentration. In separate episodes (Feb and June 2010), the Biochemistry laboratory of a tertiary-care hospital, Kolkata, India, encountered two critically ill patients with background chronic kidney disease (CKD), low urine output, and on cyanocoabalamin supplementation, who had serum vitamin B12 concentrations far exceeding expected values; even post dialysis. The B12 assays (pmol/l) were performed using electrochemiluminiscence immunoassay on Roche Elecsys 2010, the assay validity confirmed by concomitant quality control runs. The immunoassays failed to deliver results, flagged with “signal level below limit”. Biotin therapy was ruled out as a possible interferent. In the first episode, re-assay of a repeat draw yielded same outcome; outsourcing on Immulite provided concentration of >738 pmol/l. Serial dilution gave result of >29520 pmol/l on Elecsys 2010. In the second, we gained from past experience. Vitamin B12 concentration >59040 pmol/l was conveyed to the treating nephrologist the very day. The B12 immunoassay on the Elecsys 2010 employs sequential incubation steps for competitive binding that is compromised in the event of abnormally excess B12 concentration in patient sera akin to the prozone effect. This knowledge may be beneficial while assaying sera of CKD patients to avoid financial loss due unnecessary repeats and delay in turnaround time.  相似文献   

18.
Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II–V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = −0.85, P < 0.001) and creatinine (r = −0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.  相似文献   

19.
Impact of Chronic Lead Exposure on Selected Biological Markers   总被引：1，自引：0，他引：1  
Lead poisoning remains a major problem in India due to the lack of awareness of its ill effects among the clinical community. Blood lead, δ-aminolevulinic acid dehydratase (δ-ALAD) and zinc protoporphyrin (ZPP) concentrations are widely used as biomarkers for lead toxicity The present study was designed to determine the impact of chronic lead exposure on selected biological markers. A total of 250 subjects, of both sexes, ranging in age from 20 to 70 years, were recruited. On the basis of BLLs, the subjects were categorized into four groups: Group A (BLL: 0–10 μg/dl), Group B (BLL: 10–20 μg/dl). Group C (BLL: 20–30 μg/dl) and Group D (BLL: 30–40 μg/dl) having BLLs of 3.60 ± 2.71 μg/dl, 15.21 ± 2.65 μg/dl, 26.82 ± 2.53 μg/dl and 36.38 ± 2.83 μg/dl, respectively. Significant changes in biological markers due to elevated BLLs were noted. The relation of BLL and biological markers to demographic characteristics such as sex, habits, diet and substances abuse (smoking effect) were also studied in the present investigation. Males, urban population, non-vegetarians, and smokers had higher blood lead levels. δ-ALAD activity was found to be significantly lower with increased BLL (P < 0.001), while the ZPP level was significantly higher with increased BLL (P < 0.001). Further, BLL showed a negative correlation with δ-ALAD (r = −0.425, P < 0.001, N = 250) and a positive correlations with ZPP (r = 0.669, P < 0.001, N = 250). Chronic lead exposure affects the prooxidant-antioxidant equilibrium leading to cellular oxidative stress.  相似文献   

20.
The purpose of this study was to evaluate the relationship between the physicochemical properties of saliva such as flow rate, pH, buffering capacity, calcium level, total protein and total antioxidant levels in caries free and caries active children. The present study included one hundred and twenty healthy children who were divided into two groups; group I and group II comprising of age groups 7–10 and 11–14 years, respectively. Both the groups were then sub-divided equally according to gender. They were further divided into caries free and caries active with 15 children in each group. Unstimulated saliva was collected by suction method and flow rates were determined. The samples were then analyzed for pH, buffering capacity, total protein, calcium and total antioxidant capacity. The data was statistically analyzed using student t test (unpaired). The results revealed that when all these parameters were compared among the caries free and caries active children, flow rate, pH, buffering capacity were slightly reduced in caries active children, but total protein and total antioxidant capacity of saliva increased significantly in caries active children and the total calcium decreased significantly in caries active children. Within the limitation of this study, we conclude that, the physicochemical properties of saliva play a major role in the development of caries.  相似文献   

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