Toxicology mechanisms and methods
-
Toxicol. Mech. Methods · Jan 2015
3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury.
There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed. ⋯ LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.
-
Toxicol. Mech. Methods · Mar 2014
Comparative StudyThe evaluation of the reactivating and therapeutic efficacy of two novel oximes (K361 and K378) in comparison with the oxime K203 and trimedoxime in tabun-poisoned rats and mice.
The potency of two newly developed oximes (K361 and K378) to reactivate tabun-inhibited cholinesterase and to reduce acute toxicity of tabun was compared with the oxime K203 and trimedoxime using in vivo methods. The study determining percentage of reactivation of tabun-inhibited diaphragm cholinesterase in poisoned rats showed that the reactivating efficacy of the oxime K378 is slightly lower than the reactivating potency of the oxime K203 and trimedoxime while the ability of the oxime K361 to reactivate tabun-inhibited cholinesterase is markedly lower compared with the oxime K203 and trimedoxime. ⋯ Their potency to reduce acute toxicity of tabun was significantly lower compared with the oxime K203 as well as trimedoxime. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.
-
Toxicol. Mech. Methods · Jan 2013
Liver iron and serum ferritin levels are misleading for estimating cardiac, pancreatic, splenic and total body iron load in thalassemia patients: factors influencing the heterogenic distribution of excess storage iron in organs as identified by MRI T2*.
A comparative assessment of excess storage iron distribution in the liver, heart, spleen and pancreas of β-thalassemia major (β-ΤΜ) patients has been carried out using magnetic resonance imaging (MRI) relaxation times T2*. The β-ΤΜ patients (8-40 years, 11 males, 9 females) had variable serum ferritin levels (394-5603 μg/L) and were treated with deferoxamine (n = 10), deferiprone (n = 5) and deferoxamine/deferiprone combination (n = 5). MRI T2* assessment revealed that excess iron is not proportionally distributed among the organs but is stored at different concentrations in each organ and the distribution is different for each β-ΤΜ patient. ⋯ These studies contradict previous assumptions that serum ferritin and liver iron concentration is proportional to the total body iron stores in β-ΤΜ and especially cardiac iron load. The random variation in the concentration of iron in the organs of β-ΤΜ patients appears to be related to the chelation protocol, organ function, genetic, dietary, pharmacological and other factors. Monitoring of the iron load for all the organs is recommended for each β-ΤΜ patient.
-
Toxicol. Mech. Methods · May 2012
The benefit of combination of oximes for the neuroprotective efficacy of antidotal treatment of sarin-poisoned rats.
The potency of the oxime HI-6 and two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) to reduce sarin-induced acute neurotoxic signs and symptoms was evaluated in this study. Sarin-induced neurotoxicity and the neuroprotective effects of atropine alone or in combination with HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with sarin at a sublethal dose (108 μg/kg i.m.; 90% of LD(50) value) were monitored by a functional observatory battery (FOB) 24 h following sarin administration. ⋯ While atropine alone and atropine in combination with the oxime HI-6 were able to eliminate some sarin-induced neurotoxic signs and symptoms, the neuroprotective efficacy of both combinations of oximes with atropine was slightly higher. Thus, both tested combinations of oximes in combination with atropine bring a small benefit for the neuroprotective efficacy of antidotal treatment of acute sarin poisonings.
-
Toxicol. Mech. Methods · Oct 2011
Metrifonate alters antioxidant levels and caspase activity in cerebral cortex of Wistar rats.
Metrifonate (trichlorfon) is an inhibitor of acetylcholinesterase (AChE). It was used as an Alzheimer's disease (AD) drug; however, the application was withdrawn due to adverse effects. Implication of metrifonate for the antioxidant status and regulation of apoptotic processes was evaluated in the present study. ⋯ Metrifonate had only lower impact on oxidative stress in the liver. Cerebral cortex tissues had decreased AChE and increased caspase 3 activities as well as the FRAP level. Owing to the novel findings, suitability of metrifonate for AD therapy is discussed.