Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats

In view of the antioxidant properties of melatonin, the effects of melatonin on the oxidative-antioxidative status of tissues affected by diabetes, e.g. liver, heart and kidneys, were investigated in streptozotocin (STZ)-induced diabetic rats in the present study. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tissues were compared in three groups of 10 rats each (control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)). In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60 mg kg(-1) dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10 mg kg(-1) i.p. dose of melatonin per day. After 6 weeks, the rats in groups II and III had significantly lower body weights and higher blood glucose levels than the rats in group I (p < 0.001 and p < 0.001, respectively). MDA levels in the liver, kidney and heart of group II rats were higher than that of the control group (p < 0.01, p < 0.05, p < 0.01, respectively) and diabetic rats treated with melatonin (p < 0.05). The GSH, GSH-Px and SOD levels increased in diabetic rats. Treatment with melatonin changed them to near control values. Our results confirm that diabetes increases oxidative stress in many organs such as liver, kidney and heart and indicate the role of melatonin in combating the oxidative stress via its free radical-scavenging and antioxidant properties.     

Tissue lipid peroxidation and glutathione‐dependent enzyme status in patients with oral squamous cell carcinoma

We examined the extent of lipid peroxidation and the status of reduced glutathione (GSH) and the GSH‐dependent enzymes—glutathione peroxidase (GPx) and glutathione‐S‐transferase (GST)—in oral tumour tissues from 33 adult oral cancer patients and an equal number of age‐ and sex‐matched normal subjects. Diminished lipid peroxidation in the oral tumour tissue was accompanied by a significant decrease in phospholipids and an increase in the cholesterol/phospholipid (C/P) ratio. The concentration of glutathione and the activities of GPx and GST were elevated in oral tumour tissues. These findings suggest that GSH‐ and GSH‐dependent enzymes play a crucial role in tobacco‐related tumourigenesis and may be considered as markers of carcinogen exposure. Copyright © 1999 John Wiley & Sons, Ltd.     

Lipid peroxidation, vitamins C, E and reduced glutathione levels in patients with pulmonary tuberculosis

The present study examined the relationship between lipid peroxidation and vitamin C, vitamin E and reduced glutathione levels in plasma, erythrocytes and erythrocyte membranes of pulmonary tuberculosis patients and an equal number of age-and sex-matched healthy subjects. Enhanced plasma, erythrocytes and erythrocyte membrane lipid peroxidation with concomitant decline in vitamin C, vitamin E and reduced glutathione levels were found in pulmonary tuberculosis patients. The elevated lipid peroxidation and decreased vitamin C, vitamin E and reduced glutathione levels indicate the potential of oxidative damage to erythrocytes and erythrocyte membranes of pulmonary tuberculosis patients.     

Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester

The objective of this study was to assess the therapeutic advantage of glutathione ester along with cisplatin. Comparisons were made with renal reduced glutathione, enzymatic antioxidants, and lipid peroxidation levels. Cisplatin caused differential toxic effects on renal antioxidants and lipid peroxidation. However administration of glutathione ester modulates the toxic effects of cisplatin observed in renal antioxidants and lipid peroxidation. The finding that glutathione ester co-administration along with cisplatin is more effective and advantageous in protecting against the nephrotoxicity of cisplatin when it was given alone.     

Alterations of serum selenium, zinc, copper, and iron concentrations and some related antioxidant enzyme activities in patients with cutaneous leishmaniasis

The aim of this study was to measure the alterations in serum selenium (Se), copper (Cu), zinc (Zn), and iron (Fe) concentrations and their carrier proteins, ceruloplasmin (Cp), transferrin (Tf) albumin, and related antioxidant enzyme activities, erythrocyte Cu-Zn Superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in patients with cutaneous leishmaniasis (CL). Erythrocyte Cu-Zn SOD activities, serum Cu concentrations, and Cp levels were found to be significantly higher in the patients group than those of controls. However, GSH-Px and CAT activities and Se, Zn, Fe, and Tf levels were lower in patients than in the control subjects. There were positive important correlation’s between Cu-Zn SOD and Cp, Cu-Zn SOD and Cu, Cp and Cu, GSH-Px and Se, and Fe and CAT in the patients group. Our results showed that serum essential trace elements Se, Zn, Cu, and Fe concentrations and their related enzymes Cu-Zn SOD, GSH-Px, and CAT activities change in CL patients. The changes may be a part of defense strategies of organism and are induced by the hormonelike substances.     

Vectors of cutaneous leishmaniasis in north-central Venezuela

Abstract. An entomological survey was undertaken from January 1991 to February 1992 in El Ingenio, Miranda State, Venezuela, an endemic area of cutaneous leishmaniasis: prevalence of 10.7 cases per 100,000 inhabitants.
A total of 4863 female sandflies (Phlebotominae) of fourteen species were collected in Shannon traps, then dissected and examined for leishmanial infections.
Lutzomyia ovallesi (85.4%) and Lu. gomezl (11.2%) were the predominant anthropophilic species of sandfly. Fifty-one (1.19%) Lu. ovallesi and two(0.47%) Lu. gomezi had natural infection with Leishmania promastigotes. Identification of the parasites was done by using the polymerase chain reaction (PCR) and DNA hybridization. Two isolates from Lu. gomezi and forty-nine from Lu. ovallesi were typed as Leishmania braziliensis and three of the latter reacted with Le. mexicana also. This is the first report of Lu. gomezi with parasites typed as Le. braziliensis.
We concluded that Lu. ovallesi is the primary vector of cutaneous leishmaniasis in the north-central area of Venezuela and Lu. gomezi should be regarded as an additional vector.     

Expression of inducible nitric oxide synthase in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is an infectious disease caused by Leishmania parasite. The expression of inducible nitric oxide synthase (iNOS) and generation of nitric oxide in response to IFN-γ and TNF-α is important in control of infection. The aim of the study was to determine the expression of iNOS in the lesions of Leishmania tropica, and whether there was a correlation between the level of expression and the duration of the disease. Punch biopsy was performed from patients (n = 29) and iNOS immunohistochemical staining was applied. Expression of iNOS protein was detected 82.8% of patients. There was a strong expression with the duration of the disease less than 6 months (p < 0.002). These findings demonstrate that iNOS has a role in L. tropica especially during the early stages of the infection. (Mol Cell Biochem xxx: 147–149, 2005)     

Chemokines and chemokine receptors expression in the lesions of patients with American cutaneous leishmaniasis

American cutaneous leishmaniasis (ACL) presents distinct active clinical forms with different grades of severity, known as localised (LCL), intermediate (ICL) and diffuse (DCL) cutaneous leishmaniasis. LCL and DCL are associated with a polarised T-helper (Th)1 and Th2 immune response, respectively, whereas ICL, or chronic cutaneous leishmaniasis, is associated with an exacerbated immune response and a mixed cytokine expression profile. Chemokines and chemokine receptors are involved in cellular migration and are critical in the inflammatory response. Therefore, we evaluated the expression of the chemokines CXCL10, CCL4, CCL8, CCL11 and CXCL8 and the chemokine receptors CCR3, CXCR3, CCR5 and CCR7 in the lesions of patients with different clinical forms of ACL using immunohistochemistry. LCL patients exhibited a high density of CXCL10+, CCL4+ and CCL8+ cells, indicating an important role for these chemokines in the local Th1 immune response and the migration of CXCR3+ cells. LCL patients showed a higher density of CCR7+ cells than ICL or DCL patients, suggesting major dendritic cell (DC) migration to lymph nodes. Furthermore, DCL was associated with low expression levels of Th1-associated chemokines and CCL11+ epidermal DCs, which contribute to the recruitment of CCR3+ cells. Our findings also suggest an important role for epidermal cells in the induction of skin immune responses through the production of chemokines, such as CXCL10, by keratinocytes.     

Salt Stress Injury Induces Oxidative Alterations and Antioxidative Defence in the Roots of Lemna minor

Lemna minor L. roots were treated with different concentrations of NaCl. Lipid peroxidation was investigated histochemically and biochemically. At higher NaCl concentrations an increase in staining was observed in the root apices as compared to control for lipid peroxidation and loss of membrane integrity as well as an increase in contents of thiobarbituric acid reactive substance and peroxide. Both the non-enzymic antioxidants, ascorbate and glutathione increased with the NaCl concentration in the roots. Whereas an increase in superoxide dismutase, guaiacol peroxidase, and glutathione reductase activities were marked, catalase activity decreased in the roots under NaCl stress. This revised version was published online in July 2006 with corrections to the Cover Date.     

Antioxidant effect of vitamin E and glutathione on lipid peroxidation in boar semen plasma

The protective effect of vitamin E and reduced glutathione (GSH) against lipid peroxidation in boar semen plasma was studied. The lipid peroxidation, measured by the test for thiobarbituric acid reactive substances (TBARS), doubled in the presence of the lipid peroxidation Fe²⁺-sodium ascorbate-inducing system. The ascorbate-induced TBARS were inhibited by about 62% through the water-soluble vitamin E analog (TROLOX) and about 57% by GSH. In the in vivo experiments, 7 wk of oraldl-α-tocopherol acetate (1000 IU/d/animal) administration caused a significant fall in the level of the semen plasma TBARS, from 2.2±0.09 to 1.2±0.13 nmol MDA/mL. The semen plasma superoxide dismutase (SOD) and GSSG tended to increase with the time of vitamin E administration, but the increment did not reach a significant level by the seventh week. The vitamin E supplementation significantly increased the number of spermatozoa per 1 cm³ of ejaculate. The protective role of vitamin E and GSH with respect to boar semen against fatty acid peroxidation and a positive influence of vitamin E supplementation on semen quality have been evidenced.     

Exercise,depletion of antioxidants and antioxidant manipulation

Strenuous physical activity is known to increase the production of reactive oxygen species (ROS), associated with depletion of antioxidant defence. In the present work we evaluated the level of lipid peroxidation and antioxidant components in blood of sportsmen under resting conditions and compared the data obtained with those in age- and sex-matched sedentary controls. A significant increase was noted in the levels of thiobarbituric acid reactive substances (TBARS) and conjugated dienes while a decrease was observed in ascorbic acid and glutathione levels in sportsmen. α-Tocopherol was unaltered in plasma of sportsmen as compared to controls. The activity of superoxide dismutase was increased (52 per cent) and glutathione peroxidase was decreased (43 per cent) in the erythrocytes of sportsmen compared to controls. Basal glutathione levels were negatively correlated with conjugated dienes and maximal oxygen uptake (VO_2max) of the subjects. Dietary supplementation with antioxidant vitamins has been shown to be beneficial in combating oxidative stress without enhancing performance while exogenous glutathione was found to influence the endurance capacity of athletes. Such studies demonstrate the critical role played by glutathione and suggest that intervention trials should include a mixture of antioxidants rather than a single antioxidant. Copyright © 1998 John Wiley & Sons, Ltd.     

Alterations in the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells treated with potassium chromate

The involvement of reactive oxygen species in chromate-induced genotoxicity has been postulated. Because intracellular antioxidants help in eliminating the reactive species of oxygen, we have investigated both the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells exposed to nontoxic levels of chromium(VI) in culture. The cells treated with 0 200 M potassium chromate in a salts/glucose medium for 2 h were found to contain significantly lower levels of both small molecular weight and macromolecular antioxidants. In particular, the levels of glutathione and ascorbate were found to decrease with increased doses of chromate exposure in a dose-dependent manner. As little as 10 M chromate was found to decrease these small molecular weight antioxidants significantly (p<0.01). The macromolecular antioxidants, such as glutathione peroxidase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase were also significantly (p<0.01) decreased by exposing the cells to as little as 10 M chromate. Concomitantly there was a dose-dependent increase in intracellular H₂O₂ accumulation in cells exposed to chromium(VI). These results indicate that chromate-induced genotoxicity may be due, at least in part, to decreased levels of intracellular antioxidants in conjunction with an increased production of the reactive oxygen species.     

Chronic ethanol feeding causes oxidative stress in rat liver mitochondria. Prevention by S-adenosyl methionine

Oxygen utilisation during tyrosinase-catalysed oxidation of 4-hydroxyanisole was investigated using an electron spin resonance technique which employs quantitative changes in the characteristics of the electron spin resonance spectrum of the spin label 3-carbamoyl-2,5-dihydro-2,2,5–5-tetramethyl-1-H-pyridoyl-1-yloxy (CTPO) to follow changes in the oxygen concentration. Reaction mixtures containing mushroom tyrosinase (15 μg ml^?1) and differing initial concentrations of 4-hydroxyanisole in aerated phosphate buffer at pH 6.8 were incubated at room temperature. The ratio of utilisation of oxygen was found to be in approximately 1:1 molar ratio with the initial 4-hydroxyanisole concentration in the reaction mixture between 50 and 200 μmol/1 4-hydroxyanisole. The results are consistent with the stoichiometry of oxygen utilisation being accounted for by the oxidation of 4-hydroxyanisole to anisyl quinone.     

Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362?nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2?±?0.2%) and PC/Chol (4.8?±?0.2%) liposomes was higher than solution (1.9?±?0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.     

Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice

The present study investigated the prophylactic influence of melatonin against cyclophosphamide-induced oxidative stress in mouse tissues. Lipid peroxidation, reduced glutathione (GSH), glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px) and serum phosphatase levels were analyzed in brain, spleen liver, lungs, kidney and testes. Fifteen days oral administration with melatonin (0.1 mg/kg bw per day) before treatment checked the augmentation of the level of lipid peroxidation, blood GSSG and acid phosphatase caused by an acute treatment with a radiomimetic drug, cyclophosphamide (75 mg/kg bw). Cyclophosphamide-induced depletion in the level of GSH, GSH-Px and alkaline phosphatase was made up statistically significant by chronic melatonin administration given orally. The results indicate the antioxidative properties of melatonin resulting into its prophylactic property against the cyclophosphamide-induced biochemical alterations. The finding support the idea that melatonin is a potent free-radical scavenger and antioxidant.     

Lipid peroxidative damage on cadmium exposure and alterations in antioxidantsystem in rat erythrocytes: A study with relation to time

Cadmium induced lipid peroxidation (LPO) and the activity of antioxidantenzymes after the administration of a single dose of CdCl 2 (0.4 mg kg body wt, ip) was studied in rat erythrocytes.Cd intoxication increased erythrocyte LPO along with a decrease insuperoxide dismutase (SOD) up to three days of Cd treatment. Thedecrease in erythrocyte catalase (CAT) activity was marked within9 h of Cd intoxication. After three days of Cd treatment, LPOdecreased towards normal, along with an increase in erythrocyteSOC and CAT activity. Blood glutathione (GSH) decreased significantlywithin 24 h of Cd treatment, followed by an increase towards normal.Erythrocyte glutathione S-transferase (GST) activity increased up to10 days of Cd intoxication, probably in an attempt to reduce Cd toxicity.Serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase(SALP) and serum bilirubin increased up to 10 days of Cd intoxication.Blood urea increased significantly up to three days, followed by a decreasetowards normal. The results show that Cd induced LPO was associated with adecrease in antioxidant enzymes and GSH in erythrocytes; as these antioxidantsincrease in erythrocytes with recovery from Cd intoxication, the Cd inducedLPO reversed towards normal. The increase in the SGPT, SALP and serum bilirubincorrelated with LPO. The results suggest that Cd intoxication induces oxidativestress and alters the antioxidant system, resulting in oxidative damage torat erythrocytes. © Rapid Science 1998     

Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil

American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious diseasewith an estimated 1.5 million new cases per year. In Brazil, ACL represents asignificant public health problem, with approximately 30,000 new reported casesannually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte dePedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil,with 500-1,300 patients treated annually. Over the last decade, population andfamily-based candidate gene studies were conducted in Corte de Pedra, founded onprevious knowledge from studies on mice and humans. Notwithstanding limitationsrelated to sample size and power, these studies contribute important geneticbiomarkers that identify novel pathways of disease pathogenesis and possible newtherapeutic targets. The present paper is a narrative review about ACL immunogeneticsin BA, highlighting in particular the interacting roles of the wound healing geneFLI1 with interleukin-6 and genes SMAD2 andSMAD3 of the transforming growth factor beta signalling pathway.This research highlights the need for well-powered genetic and functional studies onLeishmania braziliensis infection as essential to define andvalidate the role of host genes in determining resistance/susceptibility regardingthis disease.     

How do insect herbivores cope with the extreme oxidative stress of phototoxic host plants?

Plants of the Asteraceae and Hypericaceae possess secondary compounds that induce photooxidation in insect herbivores that consume them. One of the well-established modes of action of these substances is peroxidation of membrane lipids. Some herbivores counteract these defences by avoidance of light and tissues rich in phototoxins or the ability to detoxify these secondary substances. The cytochrome P-450 polysubstrate monooxygenase systems involved, the metabolic products, and a new putative toxin pump have been described. Dietary antioxidants (β-carotene, vitamin E, ascorbate) are additional defences against phototoxicity. They reduce mortality in herbivores exposed to phototoxins and some specialist herbivores have high constitutive levels. Adapted specialist insects also have higher constitutive levels of superoxide dismutase (SOD) and respond to phototoxins in their diet by the induction of catalase (CAT), glutathione reductase (GR), and increased levels of reduced glutathione (GSH). Artificial inhibition of the enzymes SOD and CAT had little effect on phototoxicity but inhibition of GSH synthesis in herbivores enhanced photooxidative effects of administered phototoxins on lipid peroxidation. While insects have many mechanisms to overcome plant photooxidants, the Asteraceae appear to have adopted a strategy of counterattack. We suggest and provide preliminary evidence that a second group of secondary substances, the sesquiterpene lactones, occurring in the Asteraceae can attack key antioxidant defences to synergise phototoxins. © 1995 Wiley-Liss, Inc.     

Induction of Ascorbate Peroxidase and Glutathione Reductase Activities by Interactions of Mixtures of Air Pollutants

The response of ascorbate peroxidase and glutathione reductase activities in peas (Pisum sativum var. Waverex) was investigated after three weeks of exposure to mixed fumigations with S0₂, NO, and O, (0.050 parts per million each) and increasing concentrations of O, (0-0.150 parts per million). The results show that plants respond similarly to a high concentration (0.150 parts per million) of a single air pollutant (ozone) and to mixtures of air pollutants (S0₂, NO: and O,) when individual concentrations are low (0.050 parts per million each). In both cases, levels of ascorbate peroxidase and glutathione reductase activites were approximately twice those to be found in plants grown in charcoal-filtered air (p 0.01).