Study On Immunological Liver Damage And Immune Adjustment Mechanism In Guinea Pigs Caused By Trichloroethylene

BackgroundTrichloroethylene (TCE) is an organic solvent mainly used as degreaser in industry. Occupational exposure to TCE had been causing severe dermatitis in workers, with clinical manifestation of exfoliative dermatitis, erythema polymorphe, even Stevens-Johnson syndrome or acantholysis bullosa. However, the toxicity mechanism is still unknown.In the past, the studies of the toxicity of TCE focus on its hepatic and renal damage, neurotoxic responses, health risk and testicular toxicity. In recently, many studies show that it can result dermatitis with skin irritation, which occur as a result of exposure. Many scholars think the mechanism of TCE induced skin damage is TCE activated TH cells that induce a localized inflammatory reaction called delayed-type hypersensitivity or Type IV hypersensitivity, however this kind of mechanism sometime cannot explain TCE induced skin damage in clinic. At the same time, in recent years also found that many of deaths and serious liver damage caused by multiple organ failure, so sensitized by the TCE-induced liver injury has aroused great attention, and based on the TCE dermatitis drug eruption ( Dermatitis Medicamentosa-like of Trichloroethylene, DMLT) information on the cases found, TCE dermatitis patients with drug eruptions are often accompanied by severe liver injury, and multiple organ failure caused by liver injury is the leading cause of death .Therefore,we do the whole animal experiments,by comparing levels ofβ-arrestin expression, NF-κB, AP-1 activity in PBMC of each group guinea-pig to explore the guinea pig skin sensitization caused by TCE and the mechanism of immune response;In order to provide an effective theoretical basis for preventing skin damage and the development of an efficiently protective equipment. Guinea pig liver function studies related to indicators of TCE sensitized damage to the liver was analyzed.OBJECTIVEIn order to provide an effective theoretical basis for preventing skin damage and the development of an efficiently protective equipment. Guinea pig liver function studies related to indicators of TCE sensitized damage to the liver was analyzed.By comparing levels ofβ-arrestin expression, NF-κB, AP-1 activity,in PBMC of each group guinea-pig to explore the guinea pig skin sensitization caused by TCE and the mechanism of immune response.METHODSFemale guinea pigs, which were white and weighing 250-300g , were adopted .After adaptive feeding a week,the Guinea Pigs were divided to Blank control group, vehiculum (olive oil) control group, TCE and DNCB positive control in random. To monitor the status of guinea-pig growth and health, their weight was measured regularly. Adopting Guinea Pig Maximization Test (GPMT) to establish sensitized guinea pig model, to observe and record the skin reaction in guinea pig back test area and take pictures. Reaction in guinea pig skin was scored in accordance with the Skin reaction score standards in"Toxic chemicals identified technical specifications"(the Ministry of Health superintend made【2005】No.272). When the skin reaction score of test group≥1, should be ruled positive skin allergens, according to Table 2 pairs of subjects sensitized samples graded intensity.According to the different objects of the experiment , extracted PBMC from guinea pig by anticoagulant, and non-anticoagulant for the preparation of serum..The expression level ofβ-arrestin in PBMC was tested by Western Blotting; NF-κB, AP-1 activity was detected by EMSA; measurement and the indicators of liver function, including ALT, AST, TP, BUN,was tested in automatically Health Instrument.Throughout the text, data are expressed as mean±S.D. All statistical analysis was performed in SPSS12.0 software package.RESULTSThrough visual assessment, we found the skin doesn't appearing erythema and edema in blank control group, but the skin present appearing erythema and edema in DNCB positive control group. The skin present erythema and edema in TCE group. In TCE group, the ratio of immunization is 71.4%.TCE can cause derma and liver damage with the dosage used in this research.ALT, AST of sensitized guinea pigs compared with the blank control group are different,what fuond by the tests of guinea pig liver function ; ALT, AST of sensitized guinea pigs compared to non-sensitized guinea pigs was significantly increased;compared with the unexcitation guinea pigs , ALT and AST of sensitized guinea pigs were found that they have increased significantly. ALT, AST of DNCB group compared with the blank control group was no statistical significance.β-arrestin levels in PBMC of all groups of guinea pig were non-statistical significative. Compared with other groups, NF-κB activity was significantly increased in guinea pigs sensitized group, but AP-1 activity was not significantly increased, and there was statistical significance. CONCLUSIONSA certain dose of TCE can sensitize guinea pig, and it's strong allergens.Sensitization guinea pigs caused by TCE not only damaged the skin, the liver also have been injured, and this injury was related to TCE, immunological.β-arrestin may not play a role in the guinea pig skin sensitization caused by TCE .Sensitization of guinea pigs caused by TCE may activate the NF-κB, and AP-1 has not been activated.