Yucel Yavuz

Antioxidative role of melatonin in organophosphate toxicity in rats

Previous studies revealed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compound toxicity. The aim of the present study was to investigate both prophylactic and therapeutic effects of melatonin against fenthion-induced oxidative stress in rats. Therefore, we determined the changes in the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the whole blood, brain, pectoral muscle, liver, lung, heart, kidney, pancreas, and jejunum. Also, the changes in the levels of serum nitrite and nitrate, ascorbic acid, retinal, b-carotene, and ceruloplasmin were measured. In addition, activities of enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in erythrocyte of normal and experimental animals were measured. It was found that fenthion administration increased the levels of MDA in all tissues and decreased or increased the levels of GSH in some tissues. In comparison to nitrate, nitrite and ascorbic acid levels in the serum of experimental groups, there was no significant difference between groups. However, fenthion toxicity led to decrease in retinol and β-carotene levels; melatonin administration significantly prevented this decrease. Serum ceruloplasmin level was increased due to fenthion administration, but prophylactic and therapeutic melatonin administration inhibited the increase in ceruloplasmin level of serum. There was no significant change in SOD levels in melatonin-administered groups. Melatonin modulates the fenthion-induced changes in the activities of GPx and CAT. In conclusion, the results of the current study revealed that OP toxicity, induced by fenthion, activated oxidant systems in all antioxidant systems in some tissues. Melatonin administration led to a marked increase in antioxidant activity and inhibited lipid peroxidation in most of tissues.

Two cases of acute endosulfan toxicity

Background. Endosulfan is widely used in insect control and is absorbed by both humans and animals through the intestinal tract, the lungs, and the skin. Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide, with several deaths. A 9-year analysis by one of Turkeys poison control centers reported that pesticide intoxications accounted for 8.8% of 25,572 poisoning calls, with 80.3% of them relating to insecticides and 19.7% concerning rodenticides. Case Reports. We present two cases of unintentional exposure to endosulfan, one of which presented with neurological manifestations, liver toxicity, and required mechanical ventilation and emergent hemodialysis; the other had only neurological manifestations and liver toxicity. Conclusion. In cases of endosulfan poisoning, physicians must be aware of neurological manifestations, seizures, and severe metabolic acidosis. If severe metabolic acidosis is present, we suggest that hemodialysis may be an important intervention and should be performed early.

Electrocardiographic Findings of Acute Organophosphate Poisoning

In this study, we evaluated 85 patients who presented to our Emergency Department with organophosphate (OP) poisoning and discuss their associated electrocardiographic (ECG) abnormalities. Over a period of 3 years, 85 patients with OP poisoning were included in this retrospective study. ECG analysis included the rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals. The mean age was 32.2 +/- 14.9 years. Sixty percent of the patients were female. The mean corrected QT interval (QTc interval) was 0.435 +/- 0.052 s. Prolongation of the QTc interval (55.5%) was the most common ECG abnormality, followed by sinus tachycardia (31.8%). Elevation of the ST segment and low amplitude T waves were seen in 15 cases (17.6%). Patients with OP poisoning might reveal ECG abnormalities such as QTc interval prolongation or non-specific ST-T changes. QTc interval prolongation cannot be used as a unique predictive factor in determining short-term prognosis in OP poisoning. We found no clear relation between OP poisoning-related malignant ventricular dysrhythmia and QTc interval.

Lithium-induced lung toxicity in rats: the effect of caffeic acid phenethyl ester (CAPE)

Aims: We aimed to evaluate the effects of caffeic acid phenethyl ester (CAPE) on lithium (Li)‐induced lung toxicity. Methods: Twenty‐two adult male Wistar albino rats weighing between 280 and 300 g were used. The rats were randomly divided into three groups: control, Li and Li+CAPE groups. Li and CAPE were co‐administered intraperitoneally twice daily for 4 weeks. Control rats were given 0.9% NaCl during the same period. All the rats were allowed to feed ad libitum until midnight after they had received the proposed treatment. Results: In the Li group, peribronchial and intraparenchymal lymphocyte and macrophage infiltration were observed. Atypical type II pneumocytes, alveolar destruction and emphysematous changes were also detected. Lymphocyte and macrophage infiltration was significantly decreased in the Li+CAPE group compared with the Li group. Alveolar destruction, emphysematous changes and intraparenchymal mononuclear cell infiltration were also recovered to a level close to the control group. Malondialdehyde (MDA) levels were increased in the Li group compared with the control group. CAPE administration decreased the MDA levels in the Li+CAPE group. Conclusions: CAPE was found to associate with histopathological changes recovery in the lungs and oxidative stress due to Li treatment.

Caffeic acid phenethyl ester reduces mortality and sepsis-induced lung injury in rats.

Objective: Sepsis and ensuing multiorgan failure continue to be the major causes of mortality in intensive care units. Nuclear factor (NF)‐[kappa]B activation is supposed to be one of the targets in the treatment of sepsis. We studied the effectiveness of caffeic phenethyl ester (CAPE), a known NF‐[kappa]B inhibitor, in cecal ligation and puncture (CLP)‐induced sepsis and lung injury. Design: Randomized, controlled animal study. Setting: Research laboratory of an academic institution. Subjects: Female Sprague‐Dawley rats. Interventions: CLP was performed in all rats except the rats in control and sham+CAPE groups. CAPE was administered to rats at the time of operation in sham+CAPE and CAPE+sepsis0 groups. CAPE was administered to rats in the CAPE+sepsis12 group 12 hrs after CLP. Eight rats from each group were killed 24 hrs after CLP. Blood was taken for assessment of interleukin‐1, interleukin‐6, interleukin‐10, and tumor necrosis factor‐[alpha]; the right lung was removed for histopathologic examination and the left lung for biochemical examination. Apoptosis, inducible nitric oxide synthase, heat shock protein 70, malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were studied. The rest of the rats were observed for mortality. Measurements and Main Results: Mortality was significantly decreased in groups that received CAPE compared with the sepsis group. All cytokine levels were similar to control levels only in the CAPE+sepsis12 group. Apoptosis, inducible nitric oxide synthase, and heat shock protein 70 evaluation were significantly changed between all groups in the following order: control < sham+CAPE< CAPE+sepsis12 < CAPE+sepsis0 < sepsis. Malondialdehyde and catalase were increased in the sepsis group. Conclusions: CAPE reduced mortality in sepsis and improved histopathologic variables best when it was administered after the onset of sepsis.

Tissue trace and major element levels in organophosphate insecticide fenthion (Lebaycid) toxicity in rats: prophylactic and therapeutic effect of exogenous melatonin.

Organophosphate compounds are very toxic chemicals and used in widespread applications. The present study was designed to examine the role of exogenous melatonin against organophosphate toxicity in tissues (brain, heart, jejunum, kidney, liver, lung, muscle and pancreas) trace and major element levels of rats. Trace and major element concentrations in the tissues were measured in the sham group, the control group, prophylaxis with the melatonin group and therapy with the melatonin group (TM) by inductively coupled plasma-optical emission spectroscopy. Statistically significant differences among the experimental groups were detected for some tissue trace and major element concentrations. In the brain tissue, the Al, Mn and Se concentrations in the sham group were significantly higher than those in the control group (p<0.05). In the heart tissue, the Cu, Mn and Se concentrations in the sham group were significantly increased than those in the control group (p<0.05). In the kidney tissue, trace and major element concentrations in the TM group were significantly lower than those in the sham group (Fe and Mn; p<0.05, Cu, Mo, Ni, Ti, V and Zn; p<0.01). In the liver, Mg, Al, Zn and Ca concentrations in the TM group were significantly higher than those in the fenthion-treated control group (p<0.01). In the muscle tissue, element concentrations in the TM group were significantly lower when compared with the sham groups (Ca and Si; p<0.01). The Al, Cr, Mo, Ni, Si and Zn element concentrations were markedly decreased in the control group as compared with the TM group in the pancreas tissue (p<0.01). In conclusion, according to the results of the present study the major findings are that the fenthion-treated rats tissue element levels were effected and the melatonin may normalize the altered levels of some trace and major elements of the tissues in organophosphate toxicity.

Fatal acute endosulfan toxicity: a case report.

Endosulfan is an organochlorine pesticide. It is banned in the USA and Europe, but use is unrestricted for insect control. Endosulfan causes many intentional and unintentional toxicities in developing countries and in Turkey. Acute exposure to endosulfan has rarely been reported in deaths due to ingestion. Here, a fatality of 61-year-old woman of a family who was poisoned due to ingestion of endosulfan has been reported. Based on autopsy findings, patient history and toxicological results, the cause of death was determined to be acute intoxication of endosulfan and the manner, unintentional toxicities. Endosulfan has histopathological toxic effects on many organs and this toxic effect occurs within a short period after ingestion. To prevent endosulfan poisoning, the usage of it must be restricted and even prohibited. To prevent death and to accelerate improvement, the organs that have more apparent histopathological injury should be considered and early and intensive supportive treatment be initiated.

Effect of diphenhydramine on myocardial injury caused by organophosphate poisoning

Background. The aim of this experimental study was to investigate whether diphenhydramine could prevent or diminish myocardial injury caused by organophosphate poisoning as defined by histologic findings and cardiac troponin I (cTnI) levels. Methods. Twenty-four Sprague-Dawley rats were divided into equal three groups. Group 1 did not receive any agent during the experiment. Group 2 received 0.8 g/kg fenthion subcutaneously followed by normal saline (3 ml/kg) intramuscularly 30 minutes later. Group 3 received 0.8 g/kg fenthion subcutaneously, followed by diphenhydramine 30 mg/kg (in 3 ml/kg) intramuscularly 30 minutes later. All rats underwent laparotomy and thoracotomy while under anesthesia at 24 hours. Results. Treatment with diphenhydramine significantly decreased the blood cTnI levels. Additionally, diphenhydramine significantly reduced myocardial injury, including edema, inflammation, vacuolization and necrosis, as determined by pathologic scoring. Conclusion. Organophosphate poisoning can cause myocardial injury as determined by measurement of I cTnI levels. Our study demonstrates that this injury can be attenutated by the administration of diphenydramine.

Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity : Experimental study

Background. The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. Material and Method. Fourteen rabbits were divided into two equal groups (n=7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. Results. There was a significant difference in T½ values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p<0.05). Conclusion. This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

Rıvaroxaban-induced severe diffuse ıntracerebral hemorrhage.

Bleeding, the most frightening adverse effect of anticoagulants,may occur in different parts of the body.When intracerebral hemorrhage in individuals used anticoagulant drugs is compared with normal coagulation function, the volume of bleeding is increased and the prognosis is worse. There are few studies in the literature regarding the presence of intracerebral hemorrhage and the volume and prognosis of bleeding associated with rivaroxaban, a new oral anticoagulant.Therefore, the clinical and radiologic findings and follow-up of an 80-year-old male patient with intracerebral hemorrhage who uses rivaroxaban for anticoagulation are presented in this article.