Telomere shortening associated with increased levels of oxidative stress in sulfur mustard-exposed Iranian veterans.

Sulfur Mustard (SM) is the most widely used chemical weapon. It was used in World War 1 and in the more recent Iran-Iraq conflict. Genetic toxicity and DNA alkylation effects of SM in molecular and animal experiments are well documented. In this study, lymphocytic telomere lengths and serum levels of isoprostane F2α were measured using q-PCR and enzyme immunoassay-based methods in 40 Iranian veterans who had been exposed to SM between 1983-88 and 40 non-exposed healthy volunteers. The relative telomere length in SM-exposed individuals was found to be significantly shorter than the non-exposed individuals. In addition, the level of 8-isoprostane F2α was significantly higher in the SM-exposed group compared to controls. Oxidative stress can be caused by defective antioxidant responses following gene mutations or altered activities of antioxidant enzymes. Chronic respiratory diseases and infections may also increaseoxidative stress. The novel finding of this study was a the identification of 'premature ageing phenotype'. More specifically, telomere shortening which occurs naturally with aging is accelerated in SM-exposed individuals. Oxidative stress, mutations in DNA repair genes and epimutaions may be among the major mechanisms of telomere attrition. These findings may help for a novel therapeutic strategy by telomere elongation or for validation of an exposure biomarker for SM toxicity.

DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure.

Delayed effects of sulfur mustard (SM) exposure on the levels of five important damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq war and 35 unexposed controls. A major DNA damage biomarker protein - phosphorylated H2AX - along with four DNA repair proteins in cell response to the genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes from the veterans and controls using western blotting. Mean levels of XPA, MRE11, RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was significant. Even though the raised level of phosphor-H2AX in SM-poisoned group compared to the controls was not significant it was consistent with DNA damage findings confirming the severity of damage to the DNA after exposure to SM. There were correlations between the values of RAD51 and NBS1 proteins as well as XPA and MRE11 proteins. More than two decades after exposure to SM, there is still evidences of DNA damage as well as impaired repair mechanisms in cells of exposed individuals. Such disorders in cellular level may contribute to long term health problems of the SM veterans.

Review of plants and their constituents in the therapy of cerebral ischemia.

Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to cerebral hypoxia and thus to the death of neuronal cells or stroke. The limited number of medicines currently available for patients following ischemic stroke and insufficient data on efficiency of these chemicals in the treatment of stroke led us to the search for novel therapeutic approaches. Recent studies have focused on the possible capacity of natural compounds extracted from vegetables and fruits, to prevent human disabilities caused by cerebral ischemia. In this review, we will discuss some plants and their constituents that may protect brain ischemia or delay the neurological disorders following a stroke. We have reviewed different studies in scientific databases that investigate herbal compounds and their effects on cerebral ischemia.

Antigenotoxic activities of the natural dietary coumarins umbelliferone, herniarin and 7-isopentenyloxy coumarin on human lymphocytes exposed to oxidative stress.

The antigenotoxic effects of umbelliferone (UMB), herniarin (HER) and 7-isopentenyloxy coumarin (7-IP), common natural dietary coumarins, were evaluated on the human lymphocyte DNA damage using single-cell gel electrophoresis. H(2)O(2)-induced DNA break was measured based on the percentage of DNA in tail, and the antigenotoxic effects of the tested compounds were compared with that of ascorbic acid (10, 25, 50, 100 and 200 µM). UMB, HER and 7-IP did not show any genotoxicity, as compared to phosphate-buffered saline. Treatment with UMB, HER and 7-IP led to a significant reduction in the percentage of DNA in tail induced by H(2)O(2) (p < 0.001) at all concentrations. The presence of prenyl moiety in the chemical structure of 7-IP may contribute to its better antigenotoxic property, compared to UMB. The results of this study showed that 7-IP possessed the best antigenotoxic activity among the tested compounds.

Deoxyribonucleic acid damage in Iranian veterans 25 years after wartime exposure to sulfur mustard.

BACKGROUND: More than 100,000 Iranian veterans and civilians still suffer from various long-term complications due to their exposure to sulfur mustard (SM) during the Iran-Iraq war in 1983-88. The aim of the study was to investigate DNA damage of SM in veterans who were exposed to SM, 23-27 years prior to this study. MATERIALS AND METHODS: Blood samples were obtained from the veterans and healthy volunteers as negative controls. Lymphocytes were isolated from blood samples and DNA breaks were measured using single-cell microgel electrophoresis technique under alkaline conditions (comet assay). Single cells were analyzed with "Tri Tek Comet Score version 1.5" software and DNA break was measured based on the percentage of tail DNA alone, or in the presence of H2O2 (25 µM) as a positive control. RESULTS: A total of 25 SM exposed male veterans and 25 male healthy volunteers with similar ages (44.66 ± 6.2 and 42.12 ± 5.75 years, respectively) were studied. Percentage of the lymphocyte DNA damage was significantly (P < 0.01) higher in the SM-exposed individuals than in the controls (6.47 ± 0.52 and 1.31 ± 0.35, respectively). Percentages of DNA damage in the different age groups of 35-39, 40-44, 45-49, and 50-54 years in SM-exposed veterans (5.48 ± 0.17, 6.7 3 ± 1.58, 6.42 ± 0.22, and 7.27 ± 0.38, respectively) were all significantly (P < 0.05) higher than the controls (1.18 ± 0.25, 1.53 ± 0.22, 1.27 ± 0.20, and 1.42 ± 0.10, respectively). The lymphocytes incubated with H2O2 had much higher DNA damage as expected. The average of tail DNA is 42.12 ± 2.75% for control cells + H2O2 and 18.48 ± 2.14% for patients cells + H2O2; P < 0.001. CONCLUSION: SM exposure of the veterans revealed DNA damage as judged by the comet assay.

Diversin, from Ferula diversivittata protects human lymphocytes against oxidative stress induced by H2O2.

In this study, the antigenotoxic effects of diversin, a prenylated coumarin obtained from Ferula diversivittata roots were evaluated using comet assay. Isolated lymphocytes from healthy volunteers' blood samples were incubated with diversin (10, 25, 50, 100, 200 and 400 µM) alone, or in the presence of H2O2 (25 µM). DNA break was measured based on the %tail DNA and compared with different concentrations of curcumin (10, 25 and 50 µM) as the positive control. It was shown that all concentrations of diversin significantly reduce DNA damage caused by H2O2.

Effect of Erythropoietin on Serum Brain-derived Biomarkers after Carbon Monoxide Poisoning in Rats.

OBJECTIVES: Erythropoietin has been shown to exert neuroprotective effects in a variety of CNS injury models. Elevation of serum S100ß, as a glial damage marker and myelin basic protein (MBP) has been reported to occur in acute carbon monoxide (CO) poisoning. The aim of this study was to evaluate the effect of erythropoietin (EPO) on serum S100ß and MBP levels after CO poisoning in rats. MATERIALS AND METHODS: Rats were poisoned with a mixture of 3000 PPM CO in air for 65 min. After exposure, half of the rats received 5000 u/kg EPO and the rest received normal saline. At 3, 6, 12, 24, 48, 72, 144, and 336 hr after exposure samples were taken. Additionally, EPO was administered at three lower doses (625, 1250 and 2500 u/kg). The serum S100ß and MBP levels were measured using immunoenzymatic colorimetric assay. Hemoglobin level was alsomeasured. RESULTS: Serum S100ß levels in CO poisoned rats were significantly higher compared to the control group [6 hr (P< 0.01), 12 hr (P< 0. 001), 24 hr (P< 0.001), 48 hr (P< 0.008) and 72 hr (P< 0.008)]. EPO administration could significantly prevent serum S100ß elevations after 12 hr (P< 0.008) and 24 hr (P< 0.008) of CO poisoning. Serum MBP levels in CO poisoned rats were not significantly increased in comparison with the control group (P> 0.05). EPO significantly increased the hemoglobin levels. CONCLUSION: EPO could partially prevent neuronal damage. More studies are required to elucidate other aspects of these effects.

Comparison of gastric ulcerogenicity of percolated extract of Anacardium occidentale (cashew nut) with indomethacin in rats.

In traditional Iranian medicine, the core of the fruit of Anacardium occidentale (cashew nut) has been used in the management of the pain. In this study gastric ulcerogenicity effect of the percolated extract of A. occidentale was investigated in rats. The extract or indomethacin (200, 300, 400 and 800 mg/kg) was administrated orally. In the control group normal saline (5 ml/kg) was used. After getting extract, indomethacin or normal saline, animals were slaughtered. The stomachs were detached and 10ml of 2% formalin injected in to the stomach for fixing the internal coat of the gastric wall. The stomachs were then slitted open near the bigger curvature and lacerations in the glandular part were evaluated. The ulcer index was determined using j-score. Data demonstrated that the oral dose of 200mg/kg of the extract did not provoke any ulcerogenic consequence in the rat's stomach. Gastric ulcerginicity of the extract at the doses of 300, 400 and 800 mg/kg was less than the similar doses of indomethacin (p<0.01). Therefore, A. occidentale is an appropriate plant for ongoing search for establishing an analgesic agent with low gastro-intestinal side effects for clinical use.

Investigation of Hypericum perforatum extract on convulsion induced by picrotoxin in mice.

Therapeutic effect of Hypericum perforatum L. has been well known. The aim of this study is to investigate the anticonvulsant effects of Hypericum methanolic extract against seizure induced by picrotoxin in mice. The study were performed on four groups of animals. They received percolated extract of Hypericum perforatum at the doses of 25, 50, 100 & 200 mg/kg intra peritoneally. After 20 minutes animals received picrotoxin 10 mg/kg for induction of seizure. Latency of seizure, duration of seizure, death latency and percent of mortality were determined. The results indicated that latency of seizure increased in pretreated group with the dose of 50 mg/kg (p<0.01). The higher dose of extract 200 mg/kg significantly decrease duration of seizure and death latency. It maybe due to unknown ingredients in this plant or producing concentrations higher than the therapeutic level. The results showed that Hypericum perforatum L. at the dose of 50 mg/kg maybe have some beneficial effect in seizure induced by picrotoxin and this plant is suitable for continuing search in this field.

The effects of supplemental zinc and honey on wound healing in rats.

OBJECTIVES: Clinicians have long been searching for ways to obtain "super normal" wound healing. Zinc supplementation improves the healing of open wounds. Honey can improve the wound healing with its antibacterial properties. Giving supplemental zinc to normal rats can increase the wound tensile strength. This work is to study the concurrent effects of zinc and honey in wound healing of normal rats. MATERIALS AND METHODS: ONE HUNDRED AND SEVENTY TWO YOUNG RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: control, zinc-supplement, applied honey, zinc-supplement and applied honey. Two areas of skin about 4 cm² were excised. The wound area was measured every 2 days. After 3 weeks, all animals were killed and tensile strength of wounds, zinc concentration of blood and histological improvement of wounds were evaluated. The results were analyzed using two-way ANOVA and the mean differences were tested. RESULTS: It was found that honey could inhibit the bacterial growth in skin excisions. The tensile strength was increased significantly in the second to fourth groups at 21st day (P< 0.001). Also there was a significant increase in tensile strength at the same time in the fourth group. The results of the histological study showed a considerable increase in the collagen fibers, re-epithelialization and re-vascularization in the second to fourth groups. CONCLUSION: The results of the present study indicate that zinc sulfate could retard re-epithelialization, but when used with natural honey (administered topically) it could have influent wound healing in non-zinc-deficient subjects as well.

Antinociceptive and Anti-inflammatory Effects of Pistacia vera LeafExtract in Mice.

Pistacia vera L., a member of Anacardiaceae family, has been used for sedation and analgesia in traditional medicine. In this study, the antinociceptive and anti-inflammatory effects as well as acute toxicity of the aqueous and ethanolic extracts of P. vera leaves were investigated in mice. The antinociceptive activity was studied using hot plate and writhing tests. The effect of the extracts against acute inflammation was determined using xylene-induced ear edema and the activity of the extracts, against chronic inflammation, was assessed using the cotton pellet test. The LD50 values of the infusion and maceration extracts were 0.8 g/Kg and 0.79 g/Kg, respectively. The aqueous and ethanolic maceration extracts of the P. vera leaves at the doses of 0.4 g/Kg and 0.5 g/Kg (IP), respectively, showed antinociceptive effects. The pretreatment of naloxone (2 mg/Kg, SC) inhibited the activities of extracts in hot plate test, but naloxone at the same dose could not inhibit the antinociceptive activity in writhing test. The extracts also showed anti-inflammatory effects in acute and chronic anti-inflammatory tests. The ethanolic extract was as effective as diclofenac in both inflammatory tests. The aqueous and ethanolic extracts of P. vera leaves demonstrated central and peripheral antinociceptive activities dose-dependently and the central effect may be mediated by opioid system. The extracts also demonstrated anti-inflammatory effects against acute and chronic inflammation.