Objective: Evaluation of Azadirachta indica’s potential on the modulation of blood pressure parameters, antioxidant defense status, as well as immunohistochemical expressions of Peroxisome proliferator-activated receptor α (PPARα) and Bcl-2 (B-cell lymphoma 2) in rats exposed to isoproterenol was the objective of this study. Materials and Methods: Fifty rats (Rattus norvegicus) of the Wistar strain were used, with myocardial infarction induced by intraperitoneal administration of isoproterenol (ISO) for two consecutive days. Cardiac and renal biomarkers of oxidative stress, blood pressure parameters, electrocardiography, and immunohistochemical staining of PPARα and BCL2 were performed. Results: ISO toxicity heightened blood pressure parameters, aggravated oxidative processes, declined antioxidant defense system, and decreased immunohistochemical expressions of PPARα and BCL2. Interestingly, A. indica improved antioxidant status, lowered free radical generation, mitigated serum myeloperoxidase and xanthine oxidase activities, respectively. Conclusion: Mitigation of oxidative mechanisms and antihypertensive effects of Azadirachta indica suggest a positive modulatory role for the medicinal plant in isoproterenol-induced myocardial infarction.

Background & Aims: Rapamycin (sirolimus) is one of the immunosuppressive drugs that has a strong immunosuppressive effect and one of the factors that inhibits mTOR. The drug rapamycin is used in the prevention of kidney transplant rejection in kidney transplant recipients. Sirolimus is not only an inhibitor of the target of rapamycin, but also a substrate for cytochrome P450 enzyme subfamilies and for multidrug efflux pumps. The results of recent studies have shown that peroxisomal proliferation activating receptors, as a group of nuclear receptors, have multiple cellular effects and their genetic polymorphisms in connection with other genes play an important role in creating human immune system responses. The aim of this study was to determine the peroxisome proliferator alpha gene polymorphism in kidney transplant recipients treated with rapamycin and healthy controls in West Azerbaijan province (Iran) and compare them with each other. Materials & Methods: In this case-control study, 40 kidney transplant recipients treated with rapamycin one mg(as case group) and 63 healthy controls as control group were evaluated. Samplings were done in the kidney transplant clinic of Imam Khomeini Hospital (Urmia) under the supervision of a kidney specialist. The salting out method was used to genomic DNA isolation. PCR products were analyzed after enzymatic cleavage with Taq® enzyme. Data were obtained by direct counting of observed alleles and genotypes as well as the total number of samples. Then chi-square test or Fisher's exact test was used to analyze the results in the 2x2 table. The significant difference between the two groups was considered equal to 0. 05. Results: The frequency of homozygous G/G PPARα rs4253778 genotype and heterozygous G/C PPARα rs4253778 genotype observed in the healthy control group of the present study was 40 (63. 49%) and 23 (36. 51%) respectively. The homozygous C/C PPARα rs4253778 genotype was not observed in the healthy control group. The frequency of homozygous genotype G/G, heterozygous genotype G/C and homozygous genotype C/C in PPAR α rs4253778 Biomarker in the patient group was 29 (72. 5%), 9 (22. 5%) and 2 (5%) respectively. Comparison of the desired frequencies in the two groups showed that there is no statistically significant difference (P > 0. 05). The frequency of G and C alleles in the patient group is 0. 84 and 0. 16, respectively,and in healthy control it is equal to 0. 81 and 0. 19 respectively. Conclusion. In the present study, we concluded that there was no significant relationship between PPARα rs4253778 G>C polymorphism and the use of low concentration of rapamycin. Further study with more samples related to the topic is recommended.

Background and Aim: Non-alcoholic fatty liver disease is one of the most common metabolic disorders associated with a high-fat diet. The miR-34a and PPARα genes play an important role in regulating lipids and hepatic inflammation. The present experimental study investigated the effect of high-intensity interval training and moderate-intensity continuous training on the expression of miR-34a and PPARα genes in male mice with non-alcoholic fatty liver disease induced by a high-fat diet. Materials and Methods: The statistical population of the present study consisted of C57BL/6J male mice. A total of 36 male mice, weighing 21-23 grams and aged 6-8 weeks, were purchased from the Pasteur Institute of Tehran, Iran. They were subsequently housed at Pasargad Tissue and Gene Technologists Knowledge-Based Company (Histogenotech) throughout the experimental period. After a two-week acclimatization period to the new environment and familiarization with the intervention protocol, the mice were randomly divided into 6 groups (n=6 rats per group): 1) normal-fat diet (NFD; control) , 2) normal-fat diet with high-intensity interval training (NFDHIIT), 3) normal-fat diet with moderate-intensity continuous training (NFDMICT), 4) high-fat diet (HFD), 5) high-fat diet with high-intensity interval training (HFDHIIT), 6) high-fat diet with moderate-intensity continuous training (HFDMICT). Mice in the NFDHIIT, NFDMICT, HFDHIIT, and HFDMICT groups underwent 8 weeks of treadmill training after 12 weeks of either HFD or normal diet feeding. The real-time PCR technique was used to examine the expression of miR-34a and PPARα genes in each group. Results: The expression of miR-34a and PPARα genes significantly increased in the HFD group compared to the NFD group (P<0.001). It was also observed that miR-34a gene expression significantly decreased in the HFDHIIT (P<0.001) and HFDMICT (P<0.05) groups compared to the HFD group, with more pronounced changes in the HIIT group. Meanwhile, the expression of PPARα significantly increased in the HFDHIIT (P<0.001) and HFDMICT (P<0.001) groups compared to the HFD group, with a greater increase observed in the HIIT group. Conclusion: In general, it can be concluded that exercise has an effective therapeutic role in improving liver condition and related metabolic indices, and this effect varies depending on the type and intensity of the exercise.

To investigate the involvement of peroxisome proliferator-activated receptors (PPARα, PPARβ/δand PPARγ) in the reduced egg production of broiler breeder hens with unfit food intake, gene expression of these receptors was evaluated in the granulosa cells of F1 follicle by quantitative real time PCR. Hens (30 weeks old) were allocated to three different levels of feed intake (FI): Control, FI-20% (20% less than control feed intake) and FI+40% (40% more than control feed intake). These hens were maintained for 30 days with three replicates per group (10 birds / replicate; 30 birds / group). The egg production significantly decreased in two treated groups as compared to control (p<0.05). The gene expression of PPARγ was lower in the F1 follicles of FI+40% group than control and FI-20% groups (p<0.05). The transcripts of PPARα and PPARb/d genes in the F1 follicles were not significantly changed between different groups. It is concluded that increase of food intake causes drop of egg production and diminishes gene expression of PPARγ in F1 follicle while don’t change expression of PPARα and PPARb/d isoforms. Decreased mRNA level of PPARγ in F1 follicles of broiler breeder hens is the evidence of involvement of this receptor in the disorders due to high food intake.

Background: Macrophages derived foam cells are key factors in the maladaptive immune and inflammatory response.Objectives: The study of the cholesterol homeostasis and the molecular factor involved in these cells is very important in understanding the process of atherosclerosis and the mechanisms that prevent its occurrence.Materials and Methods: This experimental study investigated the effects of c9, t11-Conjugated Linoleic Acid (c9, t11-CLA). Alpha Linolenic Acid (LA), and Eicosapentaenoic Acid (EPA) on the PPARα and ACAT1 mRNA expression by Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells.Results: Incubation of CLA, LA, EPA, and synthetic ligands did not prevent increasing the cellular total cholesterol (TC). Free cholesterol (FC) is increased by Sandoz58-035 (P = 0.024) and decreased by fatty acids and Wy14643 (Pirinixic acid) (P=0.035). The pattern of distribution of %EC is similar to the EC pattern distribution. The ACAT1 mRNA expression was significantly increased by EPA (P=0.009), but c9, t11- CLA, LA, Wy14643, and Sandoz58-035 had no significant effect on the mRNA level of ACAT1 expression compared to DMSO(Dimethyl sulfoxide).Discussions: In comparison to the control of Wy14643, Sandoz58-035, c9 and t11-CLA, EPA increased the PPARα mRNA levels (P=0.024, P=0.041, P=0.043, and P=0.004, respectively), even though, LA had no significant effect on the PPARα mRNA expression (P=0.489).Conclusions: Variations in the chemical structure of fatty acids can affect their physiological function.