Toxicology letters
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In this subacute toxicity study, ethyl methanesulfonate (EMS) was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 20, 60 and 180/120 mg/kg body weight (bw)/day for a period of 28 days (for 19 days in the high-dose group). A control group was treated similarly with the vehicle, bidistilled water, only. The groups comprised 10 animals per sex, which were sacrificed after 28 days, respectively 19 days in the high-dose group, of treatment. ⋯ Organ toxicity was characterized by depression of cell proliferation (hematopoiesis and spermatogenesis) and changes suggestive of reduced metabolism and/or physiological imbalances (e.g. thymolymphatic system and thyroid gland) without signs of inflammatory or necrotic lesions. For some findings, especially the effects on the thymolymphatic system and sexual organs, it cannot be excluded that starvation-like condition contributed to the occurrence of such changes. The low dose of 20 mg/kgbw/day was basically free of adverse effects despite of a clear evidence for hemoglobin adducts.
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Organophosphorus compounds (OPs) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OP can be fatal and death is usually caused by respiratory failure. The mechanism of OP poisoning involves inhibition of acetylcholinesterase (AChE) leading to inactivation of the enzyme which has an important role in neurotransmission. ⋯ In spite of enormous efforts devoted to development of new pyridinium oximes as potential antidotes against poisoning with OP only four compounds so far have found its application in human medicine. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans. In this article the available data related to medical treatment of poisoning with OP pesticides are reviewed and the current recommendations are presented.
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Arsenic (As) is a well known toxicity inducer. Recent investigations, however, showed that it might have some therapeutic application in cancer treatment. These dual roles of arsenic have attracted a renewed research in organ pathophysiology. ⋯ Besides, arsenite exposure increased the levels of reactive oxygen species (ROS), serum TNF-alpha, As accumulation and lipid peroxidation and decreased the activities of the antioxidant enzymes and glutathione in the testicular tissue. Oral administration of taurine (at a dose of 100mg/kg body weight for 5 days) was found to be effective in counteracting As-induced oxidative stress, attenuation of testicular damages and amelioration of apoptosis in testicular tissue by controlling the reciprocal regulation of Bcl-2/Bad, phospho-ERK1/2, phospho-p38, phospho-Akt and NF-kappaB. Taurine was also found to play similar beneficial role via mitochondrial dependent pathways in As-induced testicular damages leading to apoptotic cell death.
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To investigate the role of beta receptor blockade via adenosine A(1) receptor stimulation on amitriptyline-induced QRS prolongation. ⋯ DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A(1) receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.
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Previous studies have revealed that acetaldehyde-induced cell invasion and matrix metalloproteinase-9 (MMP-9) activation and are directly involved in hepatic tumorigenesis and metastasis. Acetaldehyde is an important substance for tumor regression. We designed this study to aid in the development of powerful anti-cancer drugs with specific tumor regression and anti-metastatic potentials. ⋯ Results from our study revealed that hesperidin suppressed both acetaldehyde-activated NF-kappaB and activator protein 1 (AP-1) activity by IkappaB, JNK, and p38 signaling pathways. This resulted in the reduction of MMP-9 expression, secretion, and hepatocarcinoma cellular invasion. Our result confirmed the therapeutic potential of hesperidin an anti-metastatic and its involvement in the acetaldehyde-induced cell invasiveness of hepatocellular carcinoma in alcoholic patients.