Human & Experimental Toxicology

The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.

Quinolones (Qs) were shown to have cytotoxic effects in various cell lines including human carcinoma cells; however, mechanism of these effects was not fully understood. To investigate the possibility of the involvement of an oxidative stress induction in this mechanism of action, we examined viability of human fibroblast cells exposed to a Q antibiotic, ciprofloxacin (CPFX), and measured lipid peroxidation and total glutathione (GSH) levels, and activities of catalase (Cat), superoxide dismutases (SODs), glutathione peroxidase (GPx). The effects of vitamin E pretreatment on those parameters were also examined. Our results showed that the effect of CPFX on the viability of the cells, as determined by neutral red uptake assay, was time dependent. Cytotoxicity was not observed in the concentration range of 0.0129–0.387 mM CPFX when the cells were incubated for 24 hours. However, significant level of cytotoxicity was observed at concentrations 0.129 and 0.194 mM, and ¶ 0.129 mM, following 48 and 72 hours of exposure, respectively. When the cells were exposed to 0.194 mM CPFX for 48 hours, the level of lipid peroxidation increased and the content of total GSH decreased significantly; activities of total SOD, Mn SOD and CuZn SOD did not change; the decrease observed in the activity of Cat was not significant; and the activity of GPx was highly variable. Vitamin E pretreatment of the cells provided significant protection against CPFX-induced cytotoxicity; lowered the level of lipid peroxidation significantly, but increased the total GSH content only moderately; no change was observed in the activities of Cat and total SOD, but a significant increase in Mn SOD and a significant decrease in Cu Zn SOD were noticed. These results suggested that CPFX-induced cytotoxicity on human fibroblast cell cultures is related to oxidative stress, and vitamin E pretreatment can afford a protection.

The traditional Zulu remedy impila (Callilepis laureola) can cause acute fatal hepatocellular necrosis, especially in children. We investigated the mechanism(s) of toxicity using HuH-7 hepatocytes. Impila tubers were extracted with boiling water and the aqueous extract was used at different concentrations to study the effects on the morphology of the cells. Flow cytometry and labelling with fluorescent antibodies to tubulin were also used. At high concentrations, necrosis occurred; however, at lower concentrations, the extracts gave rise to a variety of changes including hypercondensation of chromatin, multinucleate cells, nuclear fragmentation and apoptosis. In addition, we observed destruction of cytoplasmic tubulin. These findings give further insight into the mechanism of toxicity of herbal remedies containing atractyloside.

This study compares the chronic toxicity of two anthracyclines–daunorubicin and doxorubicin, commonly used for induction of anthracycline cardiomyopathy in the rabbit model. Such a comparative study has not been published until now. Both drugs were administered intravenously to male Chinchilla rabbits in doses at 3 mg/ kg (50 mg/m²) once weekly for 10 weeks. Selected biochemical, haematological and cardiovascular parameters and body weights were regularly monitored; additionally, a histological evaluation of heart, kidney and liver was performed at the end of the experiment. In the daunorubicin group, there were marked signs of the progressive development of heart failure, like the significant increases of the pre-ejection period/left ventricular ejection time index values (up to 134%)–and histological changes within the myocardium were also observed. On the other hand, the 10-week doxorubicin administration did not cause these changes that are typical for heart injury. Haematotoxicity, manifested particularly by aplastic anaemia, was apparent in both the experimental groups. Significant body weight loss (by 45.2%) and high premature mortality (100% versus 36.4%) reflected a greater general toxicity, especially nephrotoxicity of doxorubicin in comparison with daunorubicin. Further studies are necessary to find a possible explanation for these findings.

o-Toluidine was administered to rats in the diet for four weeks at levels approximately 40, 80 and 160 mg/kg b.w. per day. Two types of diet have been used, standard (4% fat) and high fat (14% fat). Activity of antioxidant enzymes, level of glutathione and thiobarbituric acid reactive substances were measured in liver. Glutathione peroxidase was significantly increased in all treated groups while glutathione S-transferase and glutathione reductase were elevated in rats fed high-fat diet. o-Toluidine slightly enhanced catalase activity regardless of the kind of diet. Superoxide dismutase was the only enzyme whose activity was lowered in almost all treated groups. Enzymatic and nonenzymatic microsomal lipid peroxidation was enhanced 2-to 3-fold in both diet groups. Reduced glutathione level in liver was 2.3-to 4.0-fold increased in all treated groups. Our findings indicate that free radical processes can be involved in the toxic effects of o-toluidine and dietary fat can modify the response of some antioxidant enzymes to this compound.

The dust generated during weaving (carpet dust) tibbati, knotted and tuffted carpets in carpet industry was studied for its toxicity in vitro and in vivo. Carpet dust (0.5, 1.0, 2.5 and 5.0 mg/1£10 ⁶ cells) caused in vitro cytotoxicity in rat alveolar macrophages (AM) in a concentration-dependent manner. The cytotoxic, inflammatory and oxidative responses were observed in bronchoalveolar lavage fluid (BALF) of rats at 1, 4, 8 and 16 days after exposure. Rats were intratracheally exposed at 5 mg/rat individually to all three types of carpet dust. All types of carpet dusts produced increased AM, lymphocytes (PMN) population in BALF suggesting their inflammatory reactions. Cytotoxic nature of carpet dust was shown by the increased activities of lactate dehydrogenase (LDH) and acid phosphatase (AP) in BALF. Increased AM population and in vitro cytotoxicity due to carpet dusts have shown some correlation with the levels of LDH and AP activities in BALF. The gradual enhanced profile of hydrogen peroxide (H₂O₂) and nitric oxide (NO) along with depletion of reduced glutathione (GSH) in AM due to these carpet dusts are suggestive of their oxidant nature. The enzyme activities of both glutathione peroxidase (GPx) and glutathione reductase (GR) in AM were marginally reduced in exposed rats. In conclusion, the data suggest the cytotoxic, inflammatory and oxidant nature of carpet dusts. It is extrapolated that health effects on carpet weavers would be associated with the concentration and nature of airborne dust generated during weaving of carpets

Arsenic is an ubiquitous element in the environment causing oxidative burst in the exposed individuals leading to tissue damage. Antioxidants have long been known to reduce the free radical-mediated oxidative stress. Therefore, the present study was designed to determine whether supplementation of a-tocopherol (400 mg/kg body weight) and ascorbic acid (200 mg/kg body weight) to arsenic-intoxicated rats (100 ppm in drinking water) for 30 days affords protection against the oxidative stress caused by the metalloid. The arsenic-treated rats showed elevated levels of lipid peroxide, decreased levels of non-enzymatic antioxidants and activities of enzymatic antioxidants. Administration of a-tocopherol and ascorbic acid to arsenic-exposed rats showed a decrease in the level of lipid peroxidation (LPO) and enhanced levels of total sulfhydryls, reduced glutathione, ascorbic acid and a-tocopherol and so do the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase to near normal. These findings suggest thata-tocopherol and ascorbic acid prevent LPO and protect the antioxidant system in arsenic-intoxicated rats.

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 Ctreated 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.

We describe two cases of chemical necrotizing fasciitis in the upper extremities, anterior chest wall and epigastric region of the abdominal wall caused by household insecticide injection. We suggest that surgical debridement can be successfully performed in the subacute period under close observation in hemodynamically stable patients.