Volatile solvent abuse caused glomerulopathy and tubulopathy in street children.

Substance misuse among street children is a significant problem in developing countries. Volatile substances are the most abused agents. According to case reports, chronic renal diseases are common among substance-abusing street children. In this study, we examined the renal findings of 42 volatile substance-abusing street children and compared them with results from 49 healthy children (control). The street children's weight, height, and blood pressure were lower than the controls' (P < 0.05). However, their blood alkaline phosphatase and creatinine phosphokinase levels were higher (P < 0.05), and total blood protein, creatinine, and phosphorus levels were lower than the controls' (P < 0.05). Furthermore, the street children's glomerular filtration rates were within normal limits (P < 0.05), their urinary N-acetyl-beta-glucosaminidase (NAG), beta(2)-microglobulin, microalbumin, protein, calcium, phosphorus, sodium, potassium, and chloride excretions were higher, and tubular phosphate reabsorption were lower than the controls' (P < 0.05). Volatile substances have been charged with causing distal tubular disease, but increased urinary protein, NAG, beta(2)-microglobulin, microalbumin, and electrolyte excretions also result from glomerular, proximal, and distal tubular influences. We believe that increased volatile substance products in the renal parenchyma are responsible for glomerular and tubular damage. Volatile substance-abusing street children should be examined for glomerular and proximal tubular function and distal tubular acidosis.

The correlation between nitric oxide and vascular endothelial growth factor in spinal cord injury.

STUDY DESIGN: Prospective, randomized, placebo-controlled, experimental study. OBJECTIVES: The issue of whether nitric oxide (NO) production is beneficial or deleterious on ischemic injuries of the central nervous system still remains doubtful. Vascular endothelial growth factor (VEGF) is known to induce the release of NO from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. We aimed to determine the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on VEGF synthesis and free radicals in a rat model of spinal cord ischemia-reperfusion (IR) injury. SETTING: Surgical Research Laboratory of a Medical School. MATERIAL AND METHODS: Twenty-eight Wistar rats were divided into four groups as follows (n=7): Sham, IR injury, L-arginine, and L-NAME. Infrarenal abdominal aorta was occluded to induce spinal cord ischemia. L-Arginine (100 mg/kg) and L-NAME (10 mg/kg) were given before aortic occlusion. Biochemical assays of malondialdehyde (MDA), NO and VEGF were carried out in spinal cord specimens. RESULTS: L-Arginine treatment significantly increased MDA and NO, but decreased VEGF levels in spinal cord. However, nonselective inhibition of NOS with L-NAME significantly decreased MDA and NO, but increased VEGF levels. Besides, the positive linear correlation between MDA and NO, and negative linear correlations between MDA, NO and VEGF levels have also been demonstrated. CONCLUSION: Nonselective inhibition of NO synthase activity with L-NAME attenuated free radical formation and increased VEGF level when compared with NO precursor L-arginine in a rat model of spinal cord ischemia. We suggest that inhibition of NO synthase, as well as induction of VEGF, may be a therapeutic option in spinal cord IR injury.

The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C.

Diazinon is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programs. Reactive oxygen species (ROS) caused by OPIs may be involved in the toxicity of various pesticides. The aim of this study was to investigate how diazinon affects lipid peroxidation (LPO) and the antioxidant defense system in vivo and the possible ameliorating role of vitamins E and C. For this purpose, experiments were done to study the effects of DI on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit) group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT increased significantly in the DI group compared with the control group. The activity of SOD and the levels of MDA decreased significantly in the DI+Vit group compared with the DI group. The differences between the DI+Vit and control groups according to the MDA levels and the activities of both SOD and CAT were statistically significant. These results suggest that treating rats with a single dose of diazinon increases LPO and some antioxidant enzyme activities in the rat myocardium and, in addition, that single-dose treatment with a combination of vitamins E and C after the administration of diazinon can reduce LPO caused by diazinon, though this treatment was not sufficiently effective to reduce the values to those in control group.

The effects of subchronic methidathion toxicity on rat liver: role of antioxidant vitamins C and E.

Methidathion (MD) phosphorodithioic acid S-[(5-methoxy-2-oxo-1,3,4-thiadiazol-3(2H)-yl)methyl] O,O-dimethyl ester is the organophosphate insecticide (OPI) most commonly used worldwide in the pest control of crops. Subchronic MD exposure was evaluated for its effects on lipid peroxidation, the serum activities of cholinesterase (ChE), and enzymes concerning liver damage, and the protective effects of combination of vitamins E and C in albino rats. Additionally, the histopathological changes in liver tissue were examined. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body wight MD plus vitamin E plus vitamin C (MD+AO group). The MD and MD+AO groups were treated orally with MD on five days a week for 4 weeks. The serum activities of cholinesterase (ChE), alanine transferase (ALT), aspartate amiotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and the concentration of malondialdehyde (MDA) and liver histopathology were studied. In serum samples, MD significantly increased MDA concentration and ALP, AST, GGT, LDH activities but decreased the ALT and ChE activities. In the MD+AO group, MDA level and ALP, AST, LDH activities were significantly decreased and ChE activity was increased compared to the MD group. Histopathological changes found in liver tissue of rats treated with MD included were infiltration with mononuclear cells in all portal areas, sinusoidal dilatation, and focal microvesicular steatosis and hydropic degenerations in parenchymal tissue. The severity of these lesions was reduced by administration of vitamins. From these results, it can be concluded that subchronic MD causes liver damage, and lipid peroxidation may be a molecular mechanism involved in MD-induced toxicity. Furthermore, the combination of vitamins E and C can reduce the toxic effects of MD on liver tissue of rats.

Melatonin can suppress the cytotoxic effects of chlorpyrifos on human hepG2 cell lines.

The cytotoxic effect of chlorpyrifos (CP) on human HepG2 cell lines and the protective role of melatonin were investigated. TD50 of CP for HepGZ cells was also determined. The viability of HepGZ cells decreased with CP treatment in a dose-dependent manner (P <0.05). Preincubation with melatonin prior to CP application caused an increase in cell viability (P <0.05). TD50 of CP for HepG2 was determined as 84.5 microg/mL. A 1-hour melatonin treatment caused a decrease in TD50 from 84.5 to 34.1 microg/mL. The level of thiobarbituric acid reactive substance (TBARS) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in cell lines with or without melatonin administration to find out the possible mechanism of melatonin. CP caused a significant decrease in SOD, GSH-Px and CAT activities and an increase in TBARS level (P <0.05). Pre-incubation of cells with melatonin prevented an increase in TBARS. Melatonin also reduced the CP-caused inhibition of the activities of GSH-Px and CAT (P <0.05). It was suggested that CP shows a cytotoxic effect on HepG2 cell lines and melatonin can suppress cytotoxicity caused by CP with its antioxidant properties. Melatonin also reduces TD50 of CP for HepG2 cell lines.

The effects of ochratoxin A on lipid peroxidation and antioxidant enzymes: a protective role of melatonin.

Various studies indicate that the mycotoxin ochratoxin A (OTA) is a carcinogenic, genotoxic, teratogenic, immunotoxic, and nephrotoxic agent. In the present study, the activities of some enzymes in the serum and liver of rats with ochratoxicosis and the effects of melatonin on these enzymes were investigated. Rats were divided into three equal groups, each consisting of eight rats; control, OTA (289 microg/kg per day) and OTA + melatonin groups for this study. In the OTA treated group, the level of lipid peroxidation (LPO) and the activities of glutathione peroxidase (GSH-Px) were increased in the liver and serum in comparison with the control group. The activities of catalase (CAT) and superoxide dismutase (SOD) were significantly changed in the serum when compared with controls. Our results showed structural tissue damage in the liver in OTA-treated rats. Melatonin decreased the OTA-induced damage to support the antioxidant defense system and/or with free radical scavenger action.

Role of reactive oxygen species in organophosphate insecticide phosalone toxicity in erythrocytes in vitro.

Reactive oxygen species (ROS) caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study we aimed to investigate how an organophosphate insecticide, phosalone, affects lipid peroxidation (LPO) and the antioxidant defence system in vitro. For this purpose, the effects of various doses of phosalone on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in erythrocytes were studied. Each phosalone dose was incubated with a previously prepared erythrocyte sample at +4 degrees C for 0, 60 and 180 min. After incubation, the levels of malondialdehyde (MDA) and the activities of SOD, GSH-Px and CAT were determined. Phosalone caused an increase in MDA formation and a decrease in the activities of SOD, GSH-Px and CAT. However, these effects were seen only at extremely high concentrations of phosalone and these concentrations were in the lethal range. Therefore, we suggest that ROS may not involve in the toxic effects of the pesticidal use of phosalone in low concentrations.

Protection of the retina from ischemia-reperfusion injury by L-carnitine in guinea pigs.

PURPOSE: To investigate the efficacy of L-carnitine in preventing retinal injury followed by ischemia-reperfusion. METHODS: The eyes of 34 guinea pigs were used in this experiment. The guinea pigs were divided into two groups: the first group (n=17) was given L-carnitine intraperitoneally (500 mg/kg) and second group (n=17) received the same dose of saline solution. Under general anesthesia, peritomy was performed. Retro-orbital tissues were ligated for 90 minutes and ischemia was induced, followed by 4 hours of reperfusion. One of the enucleated eye was stained with hematoxylin and eosin (H&E) and retinal thicknesses were evaluated. Thiobarbituric acid reactive substances (TBARS) levels were determined in the retina of the other eye. RESULTS: Mean TBARS levels in retinal tissue were found lower in L-carnitine group (2.77 +/- 0.55 microM) than in the control group (6.57 +/- 1.19 microM), (p<0.01). On the other hand, mean retinal thickness was found to be increased in the control group (47.47 +/- 5.62 microm) when compared to the L-carnitine group (26.52 +/- 4.65 microm), (p<0.01). In correlation analysis, significantly positive relationships were found between retinal TBARS level and retinal thickness both in the control and L-carnitine groups (r=0.981, p<0.01 and r= 0.967, p<0.01 respectively). CONCLUSIONS: L-carnitine is effective in preventing retinal injury followed by ischemia-reperfusion.

Effects of cigarette smoking on lipid peroxidation.

We monitored serum malondialdehyde (MDA), an indicator of lipid peroxidation, to determine whether active cigarette smoking causes oxidative damage. The results revealed that the concentration of serum MDA was higher in cigarette smokers than in nonsmoking control subjects. No relation was found between lipid peroxidation and the number of cigarettes smoked by an individual. This finding supports the hypothesis that oxidative damage in smokers is due to the number of hours of active exposure to cigarette smoke.

Nephrotoxicity in rats induced by chlorpryfos-ethyl and ameliorating effects of antioxidants.

Nephrotoxicity induced by chlorpyrifos-ethyl (CE) and ameliorating effects of melatonin and vitamin E plus vitamin C were evaluated in rats exposed to CE. Experimental groups were as follows: control (C), CE treated (CE), vitamin E plus vitamin C treated (Vit), melatonin treated (Mel), vitamin E plus vitamin C plus CE treated (Vit+CE), and melatonin plus CE treated (Mel+CE). The rats in the CE, Vit+CE and Mel+CE groups were administered orally with CE in two equal doses of 41 mg/kg body weight (0.25 LD50). Melatonin and vitamins E and C were administrated intramuscularly at the doses of 10, 150 and 200 mg/kg, respectively. The levels of thiobarbituric acid reactive substance (TBARS) and antioxidant potential (AOP), and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. There were no significant differences in the activities of SOD and CAT between the experimental groups. The level of TBARS increased significantly (P<0.05) while AOP decreased significantly (P<0.05) in the CE group compared with the C group. GSH-Px activity was significantly (P<0.05) lower in the CE group and higher in the melatonin group than the control group. Histopathological changes were found in the kidney tissue of rats treated with CE. These were infiltration in mononuclear cells at perivascular and peritubular areas, hydropic degenerations in tubule epithelium and glomerular sclerosis. The severity of the lesions was reduced by administration of vitamins and melatonin. These results suggest that CE increases lipid peroxidation and decreases AOP by increasing oxidative stress, and that high doses of melatonin and a combination of vitamin E plus vitamin C considerably reduce the toxic effect of CE on kidney tissue of rats.

The effects of organophosphate insecticide methidathion on lipid peroxidation and anti-oxidant enzymes in rat erythrocytes: role of vitamins E and C.

The effects of organophosphate insecticide methidathion (MD) on lipid peroxidation and anti-oxidant enzymes and the ameliorating effects of a combination of vitamins E and C against MD toxicity were evaluated in rat erythrocytes. Experimental groups were: control group, MD-treated group (MD), and MD + vitamin E + vitamin C-treated group (MD + Vit). MD and MD + Vit groups were treated orally with a single dose of 8 mg/kg MD body weight at 0 hour. Vitamins E and C were injected at doses of 150 mg/kg body weight, i.m. and 200 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the MD + Vit group. Blood samples were taken 24 hours after the MD administration. The level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were studied in the erythrocytes. MDA level increased significantly in the MD group compared to the control group (P < 0.05) and decreased significantly in the MD + Vit group compared to the MD group (P < 0.05). The activities of SOD, GSH-Px, and CAT decreased in the MD group compared to the control group (P < 0.05). Only GSH-Px activity increased in the MD + Vit group compared with the MD group. These results suggest that treating rats with MD increases LPO and decreases anti-oxidant enzyme activities in erythrocytes. Furthermore, single-dose treatment with a combination of vitamins E and C 30 min after the administration of MD can reduce LPO caused by MD.

Performance and ileal histomorphology of rats treated with humic acid preparations.

As humic acid (HA) substances have antiphlogistic, adsorptive, antitoxic and antimicrobial properties, we studied the possible effects of Farmagülatör, an organic HA preparation, on the rat performance, nutrient retention, ileal histomorphology and hydroxyproline (HP) content of the ileum in two experiments. In experiment 1, 48 male Wistar albino rats were allotted to three dietary treatments. Each was randomly assigned to four cages, each with four rats. The treatments consisted of a control diet (C) with no addition of Farmagülator Dry or Liquid, a treatment with addition of 2.5 g/kg Farmagülator Dry (FDry) and a control diet containing no FDry, but the rats had 3.5 ml/l Farmagülator Liquid in drinking water (FLiquid). The experiment lasted for 20 days. Changes in live weight were recorded at days 10 and 20 of the experiment. At the end of 20 days, all rats were killed to collect samples of intestinal tissues for the measurements of histological parameters. In experiment 2, 30 rats weaned at 21 days of age were divided into three groups, each with 10 rats, and individually caged in metabolism cages for 10 days. The above three treatments were randomly assigned to rats for 10 days to record body weight and feed intake. During the last 5 days, faecal outputs were collected to determine the dry matter and nitrogen retention. In experiment 1, FDry and FLiquid rats significantly (p<0.05) gained more live weight than the control rats. Improved weight gain with HA preparations was found to be highly associated with a high epithelial surface area as there were significantly (p<0.05) longer villi heights and crypt depths and increased HP contents of ileum in the HA treated rats compared with the control rats. Although the increased weight gain in FLiquid rats did not significantly (p>0.05) differ from the control rats in experiment 2 in contrast to the result in experiment 1, the FDry rats significantly (p < 0.05) gained more weight than the control rats. This was primarily found to be associated with significantly (p<0.05) increased feed intake and nitrogen retention in FDry rats compared with the control rats. It can be concluded that HA preparations, especially FDry, caused increased weight gain in rats as overall of two experiments. The improved weight gain only by FDry preparation was associated with increased ileal epithelial mass, increased feed intake, improved feed : gain ratio and increased nitrogen retention in rats.

The effect of lidocaine/prilocaine cream on an experimental wound healing model.

The effects of lidocaine/prilocaine cream on wound healing were evaluated in this study. An incisional wound model on abdominal wall was performed on mice. A full thickness skin incision 2 cm in length was performed then it was sutured primarily with 4/0 polypropylene. In group I (n = 10) only suturing was done (control group), in group II (n = 10) lidocaine cream was applied after suturing on wound site and it was repeated for 6 days (twice in a day), in group III (n = 10) lidocaine/prilocaine cream was applied topically after suturing and repeated 6 days (twice in a day). At day 7, incisions were excised for evaluating tensile strength and 5-hydroxyproline (5-HP) values. Tensile strength values were lowest in control group and highest in lidocaine/prilocaine treatment group. 5-HP values were also expressed the same results. Both tensile strength and 5-HP values increased significantly in treatment groups in regard to the control (p < 0.05). It was concluded that lidocaine/prilocaine cream as topical anaesthetic agent had no adverse effect in an incisional wound model, furthermore it may have some beneficial effects on wound healing which remains to be evaluated and it can be used safely in day-to-day emergency practices.

The relationship between varicocele and semen nitric oxide concentrations.

We investigated the relationship between seminal plasma nitric oxide (NO) concentrations and conventional semen parameters in patients with varicocele. Semen samples were obtained from infertile patients with varicocele (n = 55) and from normal controls (n = 48). The mean NO concentration in the seminal plasma of patients with varicocele was significantly higher than that of the controls (P < 0.01). A significant negative correlation was noted between NO and sperm motility (r = -0.29, P = 0.003), NO and sperm concentration (r = -0.26, P = 0.008) and NO and normal morphology (normal %) (r = -0.25, P = 0.01). It was concluded that increased NO production may influence sperm production, motility and morphology in patients with varicocele.

Erythrocyte superoxide dismutase and glutathione peroxidase activities, and malondialdehyde and reduced glutathione levels in schizophrenic patients.

There is abundant evidence that free radicals are involved in membrane pathology in the central nervous system and that they may play a role in neuropsychiatric disorders, including schizophrenia. In this study, we investigated erythrocyte superoxide dismutase and glutathione peroxidase activities as antioxidant enzymes, malondialdehydes as a sign of lipid peroxidation, and reduced glutathione levels in schizophrenic patients. Activities of superoxide dismutase and levels of malondialdehyde in erythrocytes were greater in all patients (n=48) and in patients with acute (n=16) and chronic schizophrenia (n=32) (p<0.001 for all patients and chronic patient group; p<0.05 for acute patient group). The activities of glutathione peroxidase were lower in patients (p<0.05 for all patients and acute patient group; p=0.051 for chronic patient group) compared with the control group. Mean erythrocyte reduced glutathione was lower in patients than in controls (p<0.05). In the patient group, erythrocyte superoxide dismutase activity was positively correlated with scales and duration of disease and erythrocyte malondialdehyde concentration. These data reveal that antioxidative defense mechanisms might be impaired in schizophrenic patients.

The effect of GM-CSF (granulocyte macrophage colony stimulating factor) on doxorubicin induced tissue necrosis and wound healing.

PURPOSE: The effect of GM-CSF (granulocyte macrophage-colony stimulating factor) on tissue necrosis and ulceration induced with doxorubicin extravasation was studied. MATERIALS AND METHODS: Adult Wistar-Albino rats (n=36) were used in the study. Doxorubicin (0.4mg/300 g) was applied subcutaneously to abdominal wall. In group I (n=18), half hours after doxorubicin injection, GM-CSF 6 microg/300 mg was applied subcutaneously to the same localization. In group II (n = 18) same amount of physiologic saline (0.5 ml) were given subcutaneously to the injection site (as vehicle control groups). Group II and I were examined for induration or ulceration on 7th and 21st day. After evaluating the lesions, the injection sites were excised. Hydroxyproline (5-HP) values of dry tissue samples were calculated and histopathologic examination was done. RESULTS: At day seven there were four and eight ulceration in groups I and II, while there were four and 14 ulceration in the second evaluation at day 21st (p<0.05). 5-HP values of the groups were as follows. 97.43+/-20.39 in group land 91.34+/-22.26 in group II. Although there was an increase in epithelization, eosinophil and lymphocyte infiltration and mast cell number in group I in histopathologic examinations only the increase in angiogenesis in group I was found to be statistically significant (p<0.05). CONCLUSION: It can be concluded that GM-CSF may have beneficial effect in the treatment of doxorubicin induced tissue necrosis.