Iranian Journal of Toxicology
Volume:2 Issue: 3, Autumn 2009

Pyrethroids are important insecticides because of their high activity and low mammalian toxicity. Some studies have demonstrated that these insecticides, especially compounds with an -cyano group, produce toxic effects on various biological systems. Deltamethrin (DTM) is a Type II synthetic pyrethroid insecticide containing -cyano group and is used worldwide in agriculture, home pest control, protection of foodstuff, and disease vector control. In this study, the toxic effects of DTM were evaluated in adult male albino rats. Treated groups were given DTM orally at various dose levels (7.5, 17.5 and 27.5mg/kg b. wt./day for 45 days) with a positive control group-receiving vehicle (olive oil) only and their fertility rate and male sex organs were evaluated. Signs of toxicity and reduction in the weight of testes and accessory sex organs were observed in a dose-dependent manner. DTM brought about marked reduction in epididymal and testicular sperm counts and fertility in insecticide-exposed males. A significant decrease in the sialic acid content of testes, epididymis, ventral prostate, seminal vesicle and testicular glycogen was noticed. However, the cholesterol and protein content of testes and accessory sex organs was raised significantly in all treated groups. A significant reduction in seminal vesicle fructose and serum testosterone was also observed after DTM administration. Histopathological examination revealed severe degenerative changes in seminiferous tubules while these effects were milder at the lowest dose level. These results provide first hand information that DTM adversely affects the reproductive system of male rats.

Silymarin is obtained from Silybum marianum (milk thistle), an edible plant that has long been used medicinally for the treatment of liver-related disorders. Silymarin is a powerful hepatoprotective and antioxidant but the anticlastogenic activity, which is an important aspect of its cancer chemoprevention is not known; hence the present investigation was carried out to study its anticlastogenic and DNA protective activity in Balb/c Mouse. After silymarin injections, the mice were administered either cyclophosphamide (CP) or mitomycin C (MMC) intraperitoneally and were sacrificed at 24 hrs, 48 hrs and 72 hrs after the last dose. In vivo bone marrow micronucleus assay and Comet assay in whole blood were performed. Silymarin produced an increased number of micronucleated polychromatic erythrocytes in in vivo bone marrow micronucleus assay. Similarly it showed anticlastogenic activity against mutagens cyclophosphamide (CP) and mitomycin C (MMC) and caused significant reduction in the number of micronucleated polychromatic erythrocytes. In comet assay, it produced DNA damage, however silymarin showed DNA protective action against mutagens CP and MMC. Silymarin has chemopreventive potentials against CP and MMC induced clastogenicity in Balb/c mice. Ironically, it has also been found to induce clastogenicity and DNA damaging effects. Hence, large-scale investigations are essential to confirm the clastogenic effect before continuing the use of silymarin for therapeutic purposes.

Toxic effects of pesticides are commonly associated with reactive oxygen species damage and pentoxifylline a phosphodiesterase inhibitor is a drug well known for antioxidant properties. The purpose of this study was to evaluate the oxidative damages following a subacute exposure to malathion, an organophosphorus insecticide and pentoxifylline''s ability to counteract these effects. Malathion (200 mg/kg/day) and pentoxifylline (50 mg/kg/day) alone or in combination were administered intraperitoneally to rats and after one week, total antioxidant capacity (TAC) and total thiol groups (TTG) were measured in their blood. Pentoxifylline increased total antioxidant capacity (TAC) and total thiol groups (TTG) in blood significantly compared to malathion which decreased them. Our findings suggest that oxidative stress occurs in exposure to malathion and oxidative damage may be a contributory factor in complications associated with malathion. The results indicate that malathion exposure decreases TAC and TTG, a process involved in oxidative stress and pentoxifylline could prevent this damage.

Tobacco smoke is involved in the pathogenesis of several diseases in different body systems. Saliva is the first body fluid that confront inhaled cigarette smoke which is injurious to the oral cavity and is associated with several oral diseases and cancer.The aim of our study was to evaluate the influence of smoking on the activity of alpha-amylase in the saliva of healthy smoker individuals. alpha-amylase was measured in the supernatant of centrifuged saliva of 25 volunteer smokers, before and just after smoking a single cigarette using the standard chemical methods. The enzymatic activity showed a significant inhibition following a single cigarette. Reduction in the enzymatic activity of saliva is most probably due to the interaction between smoke aldehydes and –SH groups of the enzyme molecules. Based on the results obtained from the present study, it could be emphasized that smoking just one cigarette is sufficient to alter the salivary alpha- mylase enzymatic activities.

The mechanisms underlying the vulnerability of the brain to seizures remains unknown. Calcium ions influx and oxidative stress have been implicated in a variety of acute and chronic epileptogenic conditions. The present study was aimed at investigating the effects of nimodipine and ascorbic acid (vitamin C) alone and in combination on pentylenetetrazole (PTZ) - induced seizures in mice. The animals received nimodipine (0.5, 1, 1.5, 2 mg/Kg, i.p.), ascorbic acid (30, 100, 300 mg/Kg, i.p.) alone and in combination with sodium valproate (100 mg/Kg, i.p.), 15 and 30min prior to intra-peritonral injection of PTZ (60 mg/Kg) and the acute seizure parameters such as seizure latency, duration and protection percent were studied in each group. Ascorbic acid alone did not have any effects on the seizure parameters and the number of mice convulsing (P>0.05). Nimodipine in 2 mg/kg dose had full protective effect on PTZ- induced seizure parameters, and in lesser doses it exerted partial protective effects. The combination of ascorbic acid (300 mg/Kg) with nimodipine (1.5 mg/Kg) or sodium valproate had a significant synergistic protective effect against PTZ- induce seizures in comparison with controls(P<0.001). Ascorbic acid potentiates the anticonvulsive effects of nimodipine on PTZ-induced seizure in mice.

Pro-inflammatory cytokines, such as IL-1b and TNF- α have been suggested to be involved in the pathophysiology of depression. Tricyclic antidepressants (TCAs) are also thought to influence immune functions and concentrations of cytokines. The aim of this study was to evaluate the status of serum IL-1b and TNF-α in depressed patients who were treated, not treated, or poisoned with TCAs in comparison to healthy subjects. In this cross-sectional study, 40 patients who were admitted at Loghman-Hakim Hospital from August 2007 to January 2008 were selected. They were divided into 4 groups: healthy individuals, TCA-poisoned patients, TCA-treated depressed patients, and non-treated depressed patients with 10 subjects in each group. Serum level of IL-1b and TNF-α were compared between groups and demographic and clinical data were collected by a questioner filled out by a trained practitioner. Liver function tests, blood cell count, electrocardiography, and arterial blood gases were also performed. Complete blood analysis and demographic data showed significant differences between groups. IL-1b level was higher among females. The group of depressed patients non-treated with TCAs showed higher serum concentrations of IL-1b and TNF-α than other groups. No significant difference was observed in IL-1b and TNF-α values among healthy control, depressed TCA-treated, and TCA-poisoned groups. Depression and gender may influence the production of cytokines while neither TCAs treatment nor its overdose affects IL-1b and TNF-α.

Tricyclic antidepressants (TCAs) are widely used in psychiatric and medical conditions and are a major cause of drug overdoses and fatal poisonings in many contries. Sodium bicarbonate administration is widely recommended as the first line treatment in TCAs intoxication but the best method of its administration has not been yet established; therefore, we decided to compare the efficacy of drip infusion versus bolus administration of sodium bicarbonate in the treatment of TCAs poisoning. In this randomized clinical trial, 80 patients who had TCAs poisoning and, had been admitted to ICU were selected and divided into two groups. Both groups received 2 meq/kg of sodium bicarbonate in one bolus dose then group 1 received drip infusion of 2 litters of sodium bicarbonate (1.4% solution) additionally for the first 24 hours until the resolution of ECG and ABGs abnormalities. Patients'' outcomes in the two groups were compared. More patients, after 8 hours, attaiened conscious in the drip infusion group. (p =0.012) and also this group reached significantly more normal ECG findings at 16 and 24 hours. (p = 0.013 and 0.005) There was no significant difference in ABGs outcomes between the two methods of administration. Although our results support the beneficial effects of adding bolus sodium bicarbonate on consciousness and electrocardiographic abnormalities in TCAs poisoning patients, to identify more effective ways of sodium bicarbonate administration, further trials are warranted.

Nonsteroidal anti-inflammatory drugs are the most commonly used drugs to reduce pain and inflammation. Aceclofenac is a newer derivative of diclofenac with less gastrointestinal complications. The objective of the present study was to evaluate the toxicity profile of sustain release aceclofenac injection in rats at three dose levels, ranging from 2 to 10 mg/kg body weight. 48 swiss albino rats were divided into four groups and were treated with saline or drug at three different doses for 28 days. Various physiological, hematological and biochemical parameters were studied. zthere were no mortality and signs of toxicity at different dose levels in any of the treatment groups. Hematological as well as biochemical parameters were unaffected at three different dose levels of aceclofenac sustain release injection. These results indicated that aceclofenac injection is non-toxic even at higher dose level.