The effect of 4 weeks of endurance training and eugenol consumption on the expression of Gap43 and E-cadherin genes in the heart tissue of chlorpyrifos-poisoned mice

1.Introduction Among the various tissues of the body, the heart is one of the main and most important organs of the body to which human life depends, and any tissue and physiological damage to it disrupts human health (10) . On the other hand, today, prescribing sports activities is accepted as an effective prescription in the prevention and treatment of many diseases and improving heart function (11). However, the exact mechanism of action of exercise has not been precisely defined, and it seems that understanding biological pathways leads to a better understanding of the adaptation mechanisms of various organs, especially the heart. In this regard, the use of genomic data sets and protein expression as a powerful and reliable method can be helpful (12). Despite the importance of GAP-43, so far very few studies have been conducted to investigate the effect of exercise on GAP-43 functions in different tissues, and it is worth noting that studies have shown studies on the effect of exercise on GAP-43 protein. In the heart tissue, we did not observe. Another case that seems to be associated with heart damage is E-cadherin. E-cadherin not only restricts cell motility, but also inhibits the transcription of beta-catatin, an important factor in proliferation (18). In the myocardium, beta-catenin is involved in adhesive connections in the structure of intercellular plates and plays a vital role in the coupling of mechanical and electrical stimulation between adjacent heart cells (19). Considering the above and the importance of e-carderhin and GAP-43 on the one hand, the role and importance of physical activity in the prevention and treatment of heart injuries and the impact on various factors in the path of tissue damage and lack of research on the subject It seeks to answer the question of whether 4 weeks of endurance training and eugenol consumption affect the expression of Gap43 and E-cadherin genes in the heart tissue of chlorpyrifos-poisoned mice. 2.Methodology For the present experimental study, 40 adult male Wistar rats weighing an average of 180 to 220 g and aged 8 weeks were purchased. And randomly divided into 5 healthy control groups (n = 8), poisoned control group (n = 8), exercise group + chlorpyrifos (n = 8), eugenol + chlorpyrifos group (n = 8), exercise group + eugenol + chlorpyrifos ( 8 = n) were divided. Chlorpyrifos poisoning prepared by Sigma Aldrich USA and induced intraperitoneal dose of 3 mg / kg for 6 weeks and 5 days a week (20). Also, 250 mg / kg eugenol made by the German company Merck was fed to the supplement mice by gavage for 4 weeks and 5 days a week (21). Endurance training included 4 weeks, 5 sessions per week and each training session included 5 minutes of warm-up, 20 minutes of endurance training and 5 minutes of cooling. In the first training session, the speed started from 11 m / s and lasted for 10 minutes, gradually increasing the speed and duration of training during the implementation of the training protocol and on the last day, the speed reached 20 m / s and the duration was 26 minutes ( 20). Mice were anesthetized with chloroform solution 48 hours after the last intervention with at least 8 hours of fasting and then sacrificed. The heart tissue was quickly removed from the body and after washing with saline phosphate buffer solution, it was placed in a nitrogen tank and kept at -80 ° C. Finally, Shapiro-Wilk test, independent t-test and two-way analysis of variance using SPSS software were used to analyze the data. 3.Results The results showed that endurance training (F = 79.47, P = 0.001, ƞ = 0.799) and eugenol intake (F = 28.99, P = 0.001, ƞ = 0.592) had a significant effect on the expression of E-CADHERIN gene in heart tissue. But the interaction of endurance training and eugenol had no significant effect on the expression of E-CADHERIN gene in heart tissue (F = 0.53, P = 0.474, ƞ = 0.026). On the other hand, it was found that the expression of E-CADHERIN gene in heart tissue at the end of the period in the endurance training group was significantly higher than the control-toxic group (P = 0.001). Also, the expression of E-CADHERIN gene of heart tissue at the end of the period in the eugenol group was significantly higher than the control-toxic group (P = 0.001). Another finding showed that endurance training (F = 18.54, P = 0.001, ƞ = 0.481) and eugenol intake (F = 5.80, P = 0.026, ƞ 0.225) have a significant effect on the expression of GAP-43 gene in heart tissue, but the interaction Endurance training and eugenol had no significant effect on GAP-43 gene expression in heart tissue (F = 0.05, P = 0.812, ƞ = 0.003). It was also found that the expression of GAP-43 gene in heart tissue at the end of the period in the endurance training group was significantly higher than the control-toxic group (P = 0.001). On the other hand, the results showed that the expression of GAP-43 gene in heart tissue was significantly higher in the eugenol group than the control-poisoned group at the end of the period (P = 0.026). 4.Discussion The results of the present study showed that endurance training and eugenol increased E-CADHERIN in the heart tissue of poisoned mice. In order to explain the mechanism of effect of endurance training on e-cadre, it should be noted that the Wnt messaging pathway has an oncogenic effect that is observed in most developmental pathways. Beta-cantin is involved in the regulation and coordination of cell-cell adhesion and acts as an intracellular message transmitter in the Wnt signaling pathway, by binding and interacting with Wnt lipoprotein receptors, transmitting and increasing the accumulation of LEF complex. / Tcf-catenin-β is contained within the nucleus and increases the activation and transcription of target genes, followed by increased muscle hypertrophy (26). Petropoulos and Schergens reported that glycogen synthase minase-3 beta, one of the major proteins involved in the Wnt signaling pathway, acts as a negative regulator of muscle hypertrophy. Decreased expression of glycogen synthase kinase-3 beta and its phosphorylation is associated with increased accumulation of beta-cantin in the nucleus (27). Some studies have shown that increased expression of glycogen synthase kinase-3 beta with its activation is associated with decreased protein synthesis, which is mainly observed after endurance training (24, 26). Therefore, a significant increase in cadrerin expression due to endurance training can ultimately activate protein synthesis and strengthen the heart muscle (24). Coinciding with the increase in GAP-43 in the heart tissue of poisoned mice due to endurance training, although very little research has been done to investigate the effect of exercise and the role of GAP-43 function, and the present researchers GAP-43 protein was not observed in heart tissue.