Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways

Abstract This study aimed to investigate the role and signaling pathways of β3-AR in myocardial ischemia/reperfusion (I/R) injury, which is one of the leading causes of death worldwide. 47 male rats were randomly divided into two main groups to evaluate infarct size and molecular parameters. Rats in both groups were randomly divided into 4 groups. Control (sham), I/R (30 min ischemia/120 min reperfusion), BRL37344 (BRL) (A) (5 µg/kg single-dose pre-treatment (preT) before I/R) and BRL (B) (5 µg/kg/day preT for 10 days before I/R). Infarct size was determined with triphenyltetrazolium chloride staining and analyzed with ImageJ program. The levels of AMPK, SIRT1, mTOR, and p70SK6 responsible for cellular energy and autophagy were evaluated by western blot. Infarct size increased in the I/R group (44.84 ± 1.47%) and reduced in the single-dose and 10-day BRL-treated groups (32.22 ± 1.57%, 29.65 ± 0.55%; respectively). AMPK and SIRT1 levels were decreased by I/R but improved in the treatment groups. While mTOR and p70S6K levels increased in the I/R group, they decreased with BRL preT. BRL preT protects the heart against I/R injury. These beneficial effects are mediated in part by activation of AMPK and SIRT1, inhibition of mTOR and p70S6K, and consequently protected autophagy.

Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats.

Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study.

This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study

Abstract This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study

Abstract This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.