Zahedan Journal of Research in Medical Sciences
Volume:16 Issue: 12, Dec 2014

The herbicide paraquet (1, 1-dimethyl-4, 4-bipyridilium dichloride; PQ) is a highly toxic quaternary nitrogen herbicide. Many cases of PQ acute poisoning and death have been reported over the past few decades. The mechanisms of PQ toxicity have been reported to involve the generation of reactive oxygen species (ROS) in different organs. Several studies have suggested that the mechanism of PQ toxicity is associated with a redo cyclic reaction, which generates superoxide anion, singlet oxygen and other free radicals, leading to cellular NADPH depletion and lipid per oxidation of cell membranes. Then PQ poisoning is directed towards the use of antioxidants. There are several reports about oxidative stress in acute and chronic exposures to PQ. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1960-2013 and resulted in 378 articles. After elimination of duplicates or irrelevant papers, 70 papers were included and reviewed. Results indicated that the status of PQ toxicity and treating the toxic effects produced by PQ is presented. Nonetheless, it is reasonable for the scientific community to provide an expert review and evaluation of this herbicide and their toxic potential to produce disorders in brain, liver, kidney and lung in living organisms.

Both in vivo and in vitro studies focused on anticancer effects of saffron. Angiogenesis, which is required for embryonic development and many physiological events play crucial role in many pathological conditions such as tumor growth. Two principal genes which involved in this process are VEGF-A and its main receptor VEGFR-2. Effects of saffron on VEGF-A and VEGFR-2 gene expression were examined. In this experimental study, saffron aqueous extract obtained by Soxhlet and lyophilized using freeze dryer. MCF-7 cells were grown in RPMI1640 medium supplemented with 10 fetal bovine serum and incubated at 37ºC with 5% CO2. After 24 h of cell culture, their adhesion to the flasks investigated, then cells were treated by saffron extract at concentration of 100, 200, 400 and 800 µg/mL. Forty eight hours after treatment, total RNA extracted and cDNA was synthesized using sequence of target gene. Finally synthesized products analyzed by real time PCR to determine and compare expression level of VEGF-A and VEGFR-2. Data analysis shows inhibitory effect of saffron extract in concentration 100, 200, 400 and 800 µg/mL on VEGF-A and VEGFR-2 gene expression in MCF-7 cell line in compare with control group. For VEGF-A, most reduction can be seen in the highest concentration of saffron extract (800 µg/mL) with 17% reduction on gene expression, while critical inhibitory effects on gene expression of VEGFR-2 was 20% in 400 µg/mL concentration. Results indicate a decrease in the expression of VEGF-A and VEGFR-2 as specific biomarkers of angiogenesis in the treated samples compared to controls.

Flavonoids play significant role in the treatment of many diseases. Green tea (Camellia Sinensis L.) is a common beverage all over the world with antioxidant and detoxification effects related to the presence of flavonoids and catchins. This study aimed to investigate the protective effect of green tea on thioacetamide-induced hepatotoxicity. In this experimental study, 64 male Wistar rats were allocated to eight groups. The control group received a normal diet alone, sham group received normal saline, hepatotoxic group received thioacetamide (50 mg/kg thioacetamide for three days), other groups received a thioacetamide for three days and the alcoholic extract of bgreen tea, at minimum (50 mg/kg), moderate (100 mg/kg), and maximum (200 mg/kg) doses, glutathione (250 mg/kg), green tea (200 mg/kg) with glutathione (250 mg/kg) for 21 days (i.p.). After that, blood samples were drawn and the levels of serum alanine aminotransferase, aspartate aminotransferase, Alkaline phosphatase, total protein and albumin, as liver injury indices, were measured. The decrease of aminotransferase and alkaline phosphatase activity in the receptors of different dosages of green tea and glutathione was significant compared with the group treated by thioacetamide. Also, a significant increase was observed in total protein and albumin of serum in green tea receptors compared with thioacetamide group. The study results show the protective effect of green tea on thioacetamide-induced hepatotoxicity which is likely caused by the antioxidant effect of polyphenol compounds controlling thioacetamide activity which in turn controls the cytochrome P450 activity and neutralization of free radicals.

The aim of this study was to investigate the probable effects of radiation and consumption of garlic on estrogen, progesterone and testosterone levels. In this experimental study, 5 male and 5 female groups of rat were used: control, sham (under exposed), experimental 1 (receiving garlic extract), and experimental 2 and 3 (receiving both extract and microwaves). After a month, rats were weighed and serum levels of hormones were measured. In male the mean body weight in the sham showed a significant decrease, whereas, an increase was seen in the experimental 3 compared with sham. Also, mean plasma testosterone levels in experimental 2 and 3 were reduced. Estrogen showed this decrease in all groups. Also in all groups progesterone showed increase. In female the mean body weights in different groups showed no significant changes, whereas a significant increase was seen in serum level of progesterone in experimental 2 and 3. Although, microwaves can cause weight lost, presence of allicin and vitamins A and B in garlic can compensate some of this weight lost. Microwaves and garlic extract have fewer effects on female reproductive system, reflected only in the serum progesterone concentration. Also they reflected in the number of Leydig cells and serum testosterone and estrogen concentration. The differences observed in the responses of male and female to cell phone radiation might be attributed to the position of gonads in the body and sensitivity of testis to heat.

Colorectal cancer (CRC) is the third most prevalent and the third leading cause of cancer-related deaths in Iran. Our aim was to investigate five mononucleotide statuses among Iranian patients with sporadic colorectal cancer. In this experimental study investigation 80 sporadic CRC patients were evaluated for Microsatellite instability (MSI). The pentaplex panel including 5 quasi mononucleotide microsatellite markers (NR-21, BAT-26, BAT-25, NR-27 and NR-24) was used. The MSI analysis was performed on paired tumoral DNA from cancerous tissues and genomic DNA from whole blood. MSI carriers were identified by analysis of tumor tissue using polymerase chain reaction. Our findings showed that microsatellite instability was detected in 36 of 80 cases (45%) with colorectal cancer. MSI analysis revealed that 17 cases of MSI-H (21%), 19 MSI-L (23%) and 44 MSS (55%). Instability is observed in the tumoral DNA compared to the DNA from the normal DNA sample. The most instable markers were NR-21, NR-24 in which instability was detected in 45% of patients. Using a panel including 3 mentioned MSI markers should be more promising markers for identifying MSI status in patients with sporadic colorectal cancer.

Prenatal rat embryo exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-trans-retinoic acid (atRA). The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, in this study, the prophylactic effect of quercetin on teratogenic effects of atRA was evaluated. In this experimental study, 40 pregnant rats were divided into 7 groups. Control group received normal saline and test groups received dimethylsulfoxide (DMSO), quercetin (75 mg/kg), quercetin (200 mg/kg), atRA (25 mg/kg), atRA (25 mg/kg) plus quercetin (75 mg/kg) and atRA (25 mg/kg) plus quercetin (200 mg/kg), intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate, exencephaly and spina bifida incidence were 30.76, 61.53 and 30.76% range in group which received only atRA. Cleft palate, exencephaly and spina bifida incidence were 11.11, 16.66 and 5.55% in group which received atRA plus quercetin (75 mg/kg). However, cleft palate, exencephaly and spina bifida incidence were 10.52, 10.52 and 0% in group which received atRA plus quercetin (200 mg/kg). The means of weight and length of fetuses from rat that received atRA plus quercetin (75 mg/kg) were significantly greater than those received only atRA. It is concluded that quercetin decreased teratogenicity induced by atRA, but this subject needs more detailed evaluation.

The use of methamphetamine has been significantly increased among youth in the last decade. Methamphetamine stimulates the central nervous system and affects on the body tissues and neurotransmitters like dopamine. In this study, the effect of methamphetamine as a medicine of amphetamine group is investigated on the pituitary-gonad axis and spermatogenesis. In this experimental study, 40 mature rats with 150±10 g weight are divided into in 4 groups including 10 rats in each group. Methamphetamine powder was weighted and it was solved in the normal saline to prepare a standard solution. Three experimental groups were injected in dosage 1, 3, 5 mg/kg using insulin syringe for 14 days, every day. Then, FSH, LH and testosterone concentrations were measured from the blood samples. The testis tissue was removed and after sectioning and staining by Hematoxylin-Eosin, was inspected by optical microscope for any changes. The average values of hormones and number of seminiferous cells were analyzed in SPSS-18 software using Duncan-test. Experimental results showed that by increasing the concentration of methamphetamine, the serum level of LH and testosterone increase. While the FSH concentration decrease by increasing the level of methamphetamine. Also, investigation on the testis tissue showed that spermatogenesis has decreased on it in comparison to control group. This is because of methamphetamine effect on the gonads. The hormonal results and microscopic observations, it can conclude that using methamphetamine may cause destructive effects on pituitary-gonad axis and spermatogenesis and as a result, it may decrease fertility.

Wound healing is a complicated process that is influenced by many factors. Studies at molecular level on human and animal models have revealed several molecular changes related to the effect of diabetes on wound healing process. Increasing number of researches implicates the influence of mast cells on skin wounds healing. The present experimental study was conducted to compare systemic pentoxifylline administration on maturing process of mast cells during skin wound healing in diabetic and normoglycemic rats. In this experimental study, 48 wistar rats were divided into 2 groups of normoglycemic and diabetic and each group was divided into experimental and control. Experimental group received intraperitoneal (25 mg/kg twice a day) and control group received distilled water. The number of mast cells and their maturing process was evaluated by microscopically counting of the types of mast cells (types 1, 2, 3) by stereological methods on day 3 and 7 after surgery. In all experimental groups receiving pentoxifylline there were significant difference in the number of total mast cells, comparing normoglycemic groups (p<0.05) and also we found that in wound healing process pentoxifylline caused increasing the number of type 2 mast cells in all experimental groups (p<0.05). In all pentoxifylline treated groups delay in converting type 2 into type 3 mast cell was seen. Pentoxifylline causes decreasing mast cell degranulation during wound healing process.

Radiofrequency waves (RFW) of electronic devices and wireless communication systems affect biological systems by changing free radicals, increase lipid peroxidation and changes of antioxidant activity thereby leading to oxidative stress. This study was conducted to evaluate the RFW-induced oxidative stress in the erythrocytes and the prophylactic effect of vitamin C on these cells by measuring antioxidant enzymes activity including: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). In this experimental study, 32 adult male Sprague-Dawley rats were randomly divided into 4 experimental groups and treated daily (4 h/day) for 45 days as follows: sham, sham+vitamin C (200 mg/kg/day by nasogastric tube), RFW (exposed to 900 MHz RFW) and RFW+ vitamin C group (received vitamin C in addition to exposure to RFW). At the end of the experiment blood sample was collected by heart puncture for measurement of antioxidant enzymes activity and MDA level. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p<0.05). In the treated group vitamin C improved antioxidant enzymes activity and improved MDA level compared to the test group (p<0.05). It can be concluded that RFW causes oxidative stress in erythrocytes, and vitamin C improves the antioxidant enzymes activity and decreases MDA.

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology. Interleukin-1 receptor antagonist (IL-1Ra) is naturally occurring cytokine that inhibits interleukin-1 (IL-1) activity by binding to the IL-1 receptors without signal transduction. The aim of this study was to investigate the association between IL-1Ra gene 86bp VNTR polymorphism and systemic lupus erythematosus in the South- East of Iran. In this case control study, genetic polymorphism was analyzed in 163 SLE patients and 183 healthy controls. Genotyping of IL-1Ra VNTR polymorphism was determined by gel electrophoresis after PCR amplification. IL-1Ra VNTR alleles have different copies of 86bp tandem repeats: allele 1(four repeats), allele 2 (two repeats), allele 3 (five repeats), allele 4 (three repeats) and allele 5 (six repeats). We found an increased frequency of IL-1Ra allele 4 and 1/4 genotype in SLE patients compared to healthy controls (p=0.001 and p=0.002 respectively). Whereas, the frequency of IL-1Ra allele 3 was higher in controls than SLE patients (p=0.01). There was no any association between the IL-1Ra allele 2 and SLE. We did not observe any association between IL-1Ra polymorphism and SLE manifestations. We concluded that IL-1Ra allele 4 was involved in the pathogenesis of SLE. However, there was no association between the IL-1Ra allele 2 and SLE in South East of Iran.

The balance between T helper type 1 (Th1) and Th2 cytokines is thought to have an important role in simplified chaos of tumor progression. So we aimed to evaluate both IL-18 and IL-6 (pro-inflammatory cytokines for Th1 and trigger the Th2 cytokine release, respectively) in patients with brain tumors. In present case- control study serum samples were collected from 65 newly diagnosed patients with brain tumor and also 40 ones as control from normal population that were matched about their age and sex. Then the patients were divided into various groups according to pathologic reports of tumor type and median serum level of the cytokines determined by ELISA technique for each tumor types. Two major groups of malignant tumors (N=33) and benign tumors (N=32) was compared by nonparametric test of Kruskal-Wallis. There was significant increase in serum IL-6 level in malignant group (p< 0.01), while IL-18 was reduced in this group (p< 0.05). Acoustic schowanoma patients (N=13) divided into 2 groups, one with involvement of facial nerve (N=8) and another without this complication (N=5). We found IL-6 serum level was higher in complicated patients than the remained patients (p< 0.01). We concluded that the patients with more invasive and advanced brain tumors had more circulating levels of IL-6 in association of lower levels of IL-18, that present the immune balance due to humoral immunity in brain tumors is polarized in favor of Th2.

The liver plays a central role in insulin-like growth factor (IGF) system homeostasis. We examine the protective aerobic training on the IGF system following doxorubicin (DOX) induced hepatotoxicity. In this experimental study 48 Wistar male rats (weighing 257±28 g) were divided into 6 groups: (1) control+placebo (2) control+DOX 10 mg/kg (3) control+DOX 20 mg/kg (4) training+placebo (5) training+DOX 10 mg/kg (6) training+DOX 20 mg/kg. Hepatotoxicity was induced by DOX (10 and 20 mg/kg). Rats in the 4, 5 and 6 groups performed treadmill running of 25 to 54 min/day and 15 to 20 m/min, 5 days/wk for 6 weeks. While, DOX 10 mg/kg administration result in an insignificant increase in IGF-1 and IGF-1/IGFBP-3 and an insignificant decrease in IGFBP-3, DOX 20 mg/kg administration caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the group 1. Three weeks of the endurance exercise resulted in a significant decrease of IGF-1 and IGF-1/IGFBP-3 levels, and significant increase in IGFBP-3, as compared to the group 1. Furthermore, after 3 weeks endurance training and DOX treatment with 10 mg/kg an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to group 2. DOX hepatotoxicity is dose-dependent, acute administration of DOX 20 mg/kg caused an imbalance in the IGF system and protective aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

Epilepsy is a neurological disorder which is modulated by different situations and activities. Stress and exercise can have effects on epilepsy; it can reduce or increase its occurrence. We investigated the effect of acute and chronic stress and also regular moderate exercise on the epileptogenesis. In this experimental study, 82 male Wistar rats divided into 7 groups including 2 exercised and stressed categories, received 40 mg/kg pentylenetetrazol (PTZ) every 48 h up to 13 injections. Then the convulsive behavior was rated by Racine scale. The acute stress was applied by a 30 min swimming session in the water with temperatures of 20, 25 and 32ºC. The chronic stress was created by repeated sessions of 30 min daily swimming for 5 days in 20ºC water. The exercise was a 60 min swimming daily, 5 days a week and for 8 weeks in 25 and 32ºC. We demonstrated that the acute stress showed a decrease in kindling threshold, except for the stress in 25ºC water which lowered the kindling rate. Similarly, the chronic stress decreased the kindling threshold in the first 5 injections. The exercise did not reduce the kindling threshold but did reduce the kindling rate in both 25 and 32ºC water. It is concluded that the swimming stress enhanced the kindling process, but the swimming exercise prevented the kindling. Therefore, the animal learns to cope with the condition in a repeated regular physical activity.

Mycobacterium bovis is the causative agent of bovine tuberculosis and belongs to the Mycobacterium tuberculosis complex. M. bovis usually carries only one or a few copies of the insertion sequence IS6110 in its genome. The aim of this study was evaluation of copy number of IS6110 in M. bovis isolates by restriction fragment length polymorphism (RFLP) method. In this experimental study, 25 lymph node specimens of tuberculin-positive cattle were collected and cultured by standard methods, afterward genomic DNA was extracted by chloroform-isoamyl alcohol. Genetic studies were conducted by Pvull and DNA hybridization with IS6110. Two isolates displayed more than of 4 copies of IS6110 by RFLP (IS6110-RFLP) method. The results of this study are unique and specific in Iran but reported in the world rarely. Therefore the new strains of M. bovis imported to Iran from other countries of the world.