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Proanthocyanidins On The Protective Effect Of Trans Fatty Acids In Cardiovascular Toxicity In Rats

Posted on:2014-09-13Degree:MasterType:Thesis
Country:ChinaCandidate:W F WangFull Text:PDF
GTID:2264330401470565Subject:Health Toxicology
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Objective:To observe the toxic cardiovascular action of trans fatty acids (TFA) in theSprague Dawley (SD) rats and explore the protection effects and the mechanisms ofProanthocyanidin (PC) on the cardiovascular injuries following TFA, which providedthe experimental basis for the protection of PC on the cardiovascular injuriesfollowing TFA.Methods:In the experiments, PC and TFA were applied in the adult, healthy SD rats, withthe ages of six weeks. In total forty-eight SD rats (24male and24female) wererandomized into six groups, namely, control group, TFA group, PC control group andthree PC protection groups with low, middle or high dose. In the control group,intragastric administration of distilled water was applied; in the TFA group,intragastric administration of TFA (100mg/kg) was applied; in the PC control group,intragastric administration of PC (50mg/kg) was applied; in the three PC protectiongroups, in the morning, intragastric administration of TFA with the same dose (100mg/kg) was used, and in the afternoon, different doses of PC were applied in the threegroups, respectively, with the doses as25mg/kg,50mg/kg or100mg/kg. Theexperiments lasted for eight weeks, once every other day, with the volume of the fluidtaken once as10ml/kg.After the last intragastric administration, the animals were restrained to food for12hours and the weights were measured. After anesthesia, the blood from the heartwas collected and the serum was isolated. The rats were sacrificed and the organswere isolated and the organ coefficients and the visceral fat weight were measured.With the Automatic biochemical analyzer, the contents of lipid TC, TG, LDL andHDL in the serum of animals in different groups were measured. The activity ofTNF-α, HO-1, NOS, LDH, SOD and GSH-Px enzyme and the content of MDA in theserum were detected with the kit. The total protein level was detected with theBradford method and routine HE staining was applied to observe the pathomorphological changes of the aorta and the liver. All the data were analyzedwith the SPSS13.0software and were expressed as Mean±SD. For the comparisonamong groups, the least significant difference t-test was used, and a level of P <0.05was considered statistically significant.Results:1. Changes of weights:After the experiments, the final weights of animals in different groups variedobviously. The weights of rats in the TFA group were obviously higher than that in thecontrol group (P<0.05). After the PC protection, the weights had the tendency ofdecreasing with the increasing of dose, which were significantly different from thosein the simple TFA group.2. Changes of organ coefficients and visceral fat weight:The organ coefficients of liver and kidney in the TFA group were higher thanthose in the control group (P<0.05). Following PC protection, the organ coefficientsof liver and kidney in the PC group with high dose were lower than those in the TFAgroup (P<0.05). The perirenal fat wight and the perirenal fat/body ratio in the TFAgroup were higher than those in the control group (P<0.05). After the PC protection,compared to those in the TFA group, those in the PC group with high dose weredecreased (P<0.05). There were no significant differences of the peri-epididymis fatweight and peri-epididymis fat/body ratio between the PC groups with different doses,control groups and TFA groups (P>0.05).3. Morphological changes of aorta:Under the microscope, in the control group, the endothelial cells of the aortawere full, continuous and smooth without superficial cell adhesion. The gap below theinner membrance was narrow. The smooth muscle in mid layer was clear, withuniformed order of cells without proliferation. In the TFA group, the vessel walls werebecoming thicker, with unsmooth inner membrance and incomplete endothelial cellswith continuous deficit. The collagen fibers in the base layer were exposed, andplenty of mononuclear cells were adhesion to the surface of endothelium or below theendothelium. The gap below the endothelium was becoming wider, and the internal elastic lamina was isolated. The smooth muscle cells in the shallow layer wereproliferated with irregular arrangement, in which the tendency of smooth muscle celltransmitting into endothelium could be seen. In the PC protection group, theendothelium was smooth, with some mononuclear cells adhesion locally. Theendothelium cells were deficit and the smooth muscle cells were proliferated. Themorphological changes of the aorta in the three PC groups with different doses weresimilar.4. Changes of lipid in serum:The contents of TC, TG and LDL-C in the serum of rats in TFA group werehigher than those in the control group (P<0.05). Following PC protection, thecontents of TC, TG and LDL-C in the serum of rats in PC groups with middle andhigh doses were lower than those in the TFA group (P<0.05). Compared with those inthe TFA group, there was no significant difference of the HDL-C content in the serumof three PC groups with different doses (P>0.05).5. Changes of seroenzyme indexes:After PC protection, both PC with middle and high doses could decrease thecontent of HO-1in the serum of rats. PC with high dose could decrease the content ofTNF-α, which was significantly different compared with that in the TFA group(P<0.05). The contents of HO-1and TNF-a in the serum of rats in the TFA groupwere higher than those in the control group (P<0.05). In the TFA group, the NOScontent was lower but the LDH content was higher than that in the control group(P<0.05). The NOS content in the serum of PC protection group with high dose washigher than that in the TFA group (P<0.05). The LDH content in both PC protectiongroups with middle and high doses were decreased compared with that in the TFAgroup, with significant difference (P<0.05).6. Changes of peroxide indexes in the lipid of serum:The SOD and GSH-Px activity in the serum of TFA group was lower than that inthe control group, but the MDA content in the serum was higher than that in thecontrol group (P<0.05). After PC protection, the SOD and GSH-Px activity in theserum was increased with the increasing of PC dose, and the activity in PC group with high dose was obviously higher than that in the TFA group (P<0.05), but the MDAcontent in both the PC groups with middle and high dose was apparently lower thanthat in the TFA group (P<0.05).Conclusions:1.TFA has a significant toxicity on the SD rats cardiovascular system.2.Suitable dose of PC canreduce the toxicity of cardiovascularsystem and pvotectit.The mechanism may have a relationship with resistance to oxidative damage.
Keywords/Search Tags:Trans fatty acids (TFA), Proanthocyanidin (PC), Sprague Dawley (SD)rats, cardiovascular toxicity, serum lipoprotein
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