Iranian Journal of Toxicology
Volume:1 Issue: 1, Spring 2007

Rhabdomyolysis results from acute muscle fibers necrosis with leakage of muscleconstituents into blood. It is a common and potentially lethal clinical syndrome. Acute renalfailure (ARF) which appears in 15%-33% of patients with rhabdomyolysis is due to theMyoglobinuria. Intoxications, inherited diseases, muscle compression or overexertion, orinflammatory processes, are among other disorders cause rhabdomyolysis. No cause is found insome cases. To determine the most common etiologic factors underlying development ofrhabdomyolysis and related complications in poisoned patients the present study was carried out.Material: We describe 56 patients who were hospitalized in toxicology ICU of "LoghmanHakim Hospital", the biggest toxicology unit in the world, between February 2002 and March2003. Of 813 patients, 56 patients with an acute overdose and serum creatine kinase (CK) morethan 5 times the upper limit of normal (>975 IU/L) were included. Patients with recentmyocardial infarction or stroke were excluded. For all, the highest values of serum CK, serumcreatinine, and urine hemoglobin, and red blood cells were recorded. Of the 56 patients, 5 were female and 51 were male (median age, 32 yr; range, 16-76yr).The most common intoxication responsible for rhabdomyolysis, included opium(42.5%),tricyclic antidepressants(19.5%), and benzodiazepines(9%). In 5%, no cause was found. Acuterenal failure (ARF) was present in 16 (29%) patients, of whom 15 were male. Five male subjectswith ARF required hemodialysis which all of them died (9%). Hemodialysed ARF had asignificant correlation with death. Urine dipstick for heme was positive in 96.5%. Patients using illicit drugs were at risk for rhabdomyolysis. With appropriate carefor prevention of ARF, death is rare.

1Department of Natural Resources and medicinal plants, Agriculture center for Higher Education,Agricultural Research and Education Organization. Karaj2Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences.PO Box 13145-784. Tehran, IranIn this study, two different procedures; one using immunoaffinity clean – up and anotherusing mycosep clean- up columns were used. The immunoaffinity and mycosep columnsused in our study were Ochra Test; Ochraprep and the new mycosep 229 ochrarespectively. In all procedures, separations were carried out by high performance liquidchromatography and fluorescence detection. The mean recovery of OTA using theprocedure with mycosep column at spiking level of 30 and 40 µg/kg were 65.1 % with aRSD 11.92 % and 84.52 % with a RSD 9.97 % respectively. The mean recovery of OTAin the other procedures with raisin samples purified on immunoaffinity column in spikinglevels; 7.5, 10, 15, 20 and 25 µg/kg varied from 50.96 % to 100.08 % with the RSDranged 5.35% to 36.43%. The limit of detection for the method of ochratoxin A in rasinpurified with mycosep and immunoaffinity column were 20 and 5 µg/kg, respectively.

In the following we have investigated the cytotoxic mechanisms of the oxyanion chromate (Cr(VI)). Cr(VI) cytotoxicity was associated with reactive oxygen species (ROS) formation, lipid peroxidationand loss of mitochondrial membrane potential which were prevented by catalase, antioxidants and ROSscavengers. Hepatocyte glutathione was also rapidly oxidized. Cr(VI) reduction was inhibited inglutathione depleted hepatocytes and glutathione depleted hepatocytes were also much more resistantto chromate induced cytotoxicity, ROS formation and lipid peroxidation. Inhibitors of cytochromeP450 or P450 reductase but not DT diaphorase prevented Cr(VI) induced cytotoxicity and ROSformation. This suggests that Cr(VI) is reductively activated by both glutathione and cytochrome P450.Cr(VI) cytotoxicity also involved lysosomal injury and protease activation which were prevented bylysosomotropic agents, endocytosis inhibitors, protease inhibitors and ROS scavengers. In conclusionCr(VI) induced cytotoxicity could be attributed to oxidative stress and lysosomal damage.

Malathion is a widely used organophosphorus (OP) insecticide which its residue in foodstuffs must be detected continuously. A simple method of solid-phase extraction (SPE) andfurther thin layer chromatography (TLC) for extraction and detection of Malathion in wheatflour is introduced. Briefly, flour samples were mixed with various concentrations ofMalathion and 1 M potassium phosphate buffer (pH=6.0), and washed with methanol.Methanolic extracts were divided into 3 equal volumes and each volume was separatelypoured in SPE columns and eluted with 3 different solvents. Eluates were evaporated undera steam of nitrogen at room temperature. Extracts were reconstituted in 100 µL of solventsand 10 µL of them were spotted on TLC plates. After development of TLC plates, theywere sprayed with palladium chloride reagent evenly. The spots were evaluated visuallyand spectrophotometrically. Results showed that SPE with methanol has the highestrecovery.Regarding importance of measuring Malathion, the present method can be used by manyreference laboratories for detection of Malathion residue in food stuff.

Scorpion sting is one of the common causes of emergency referrals in some regionsand most people consider it a dreadful condition. In most warm and arid regionsscorpion venom antiserum is used routinely. Considering the high prevalence ofscorpion stings in Markazi Province of Iran and its usual benign natural history, wedecided to compare those who received antiserum with the ones who did not.In this quasi-experimental clinical trial, which was conducted in 2003 and 2004, 140patients who were admitted for scorpion stings in emergency department of Arak ValiAsr Hospital were evaluated for complications. All the 72 patients who were referredin 2003 received antiserum; however, in none of the cases who were hospitalized in2004 the antiserum was administered and they were treated conservatively.The frequency of mild, moderate, and severe symptoms in the antiserum group were86%, 12.5%, and 1.38% and in those who did not receive antiserum were 82.3%,17.6%, 0% respectively which revealed no difference.In antiserum group and conservative treatment group the incidence of complicationswere as follows: skin lesions (59.72% vs. 64.7%), constitutional signs (27.7% vs.25%), agitation (18.5% vs. 14.7%), muscle spasm (2.77% vs. 1.47%), and respiratorydistress (1.38% vs. 1.40%) which were statistically similar rates. No mortalityoccurred.Regarding the lack of difference in the severity of symptoms and the frequency ofcomplications between those who received antiserum and the ones who did not, itseems reasonable to withhold scorpion antiserum administration in the MarkaziProvince of Iran and to treat the scorpion sting patients conservatively which is inaccordance with Pasteur Institute of Iran''s recommendation.

Aluminium phosphide poisoning known as “Rice tablet poisoning” in Iran is oneof the most common types of lethal poisoning that has achieved more attention in recent years;therefore the Iranian Ministry of Health has forbidden its sale. The present study was designedand conducted to investigate consumption and mortality of rice tablets in Loghman–HakimPoisoning Center. This descriptive study was carried out from March 2005 through March2007. All inpatients that were suspicious of botanic or chemical rice tablets ingestion wereincluded and their sex, age, month of admission (1-24), length of stay and outcome weredocumented. Patients’ data were collected in questionnaires by observational method. During the 24 month of study 340 subjects were admitted, of whom 232(68.2%) werereferred in the second year. One hundred (29.4%) of the patients, most of them females (59%),died. There were no significant correlations among sex, age and outcome. Aluminium phosphide poisoning and its mortality is increasing in Iran. Therefore,restriction of easy accessibility to this poison by the government is recommended.

Impurities in narcotic illicit drugs exist and can cause acute or chronictoxicity in abusers. Heavy metals such as, As, Pb, Fe, Zn and Cu can act as metallicpoisons in these circumstances. Toxic metals in opium, heroin and hashish are veryimportant in forensic and clinical toxicology. The aim of this study was measuringthese impurities in narcotics available in illicit markets in Iran by physical andchemical methods. In this study, we used X-ray fluorescence to recognizemetallic elements in narcotic drugs and atomic absorption spectrometry, atomicemission spectrometry and atomic hydride generation spectrometry for measuringtheir concentration. We found excessive amounts of toxic elements e.g. As, Pb, Fe, Cu and Znand nontoxic ones like K, Ca in studied materials. Concentration of these elementsand their proportions were determined. After consumption of narcotic some impurities would enter their bodiesand can cause toxicity. By comparing normal concentrations of these elements inbody and with regards to measured concentrations, we can diagnose acute or chronictoxicity of these elements after narcotic abuse.

In this study we have investigated the cytotoxic mechanisms of arsenite As(III) inisolated rat hepatocytes. Our experimental design was based on Accelerated CytotoxicMechanisms Screening technique (ACMS) using the LC502hr concentration, 50 µM. Arsenitecytotoxicity was associated with little oxidative stress and lysosomal damage did not occur.However arsenite cytotoxicity was associated with loss of mitochondrial membrane potential,which was inhibited by the ATP generators fructose, xylitol and glutamine; and also by MPTpore sealing agents such as carnitine, cyclosporin and trifluoperazine.in Arsenite inducedcytotoxicity, mitochondrial membrane potential decline and also ROS formation weresignificantly increased by inactivating hepatocyte methionine synthase or hepatocyte methyltransferase but were prevented by methyl donors such as betaine, methionine, folic acid andmethylcobalamine and this suggests that arsenite is detoxified by reductive methylation. Theactivity of caspase-3 enzyme the main mediator of apoptosis, was also significantly increased,following incubation of hepatocytes with different concentrations of arsenite. In conclusionarsenite induced cytotoxicity could be attributed to mitochondrial toxicity and ATP depletion.