Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, ß-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, ß-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500 mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aß peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aß plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

Treadmill exercise with nanoselenium supplementation affects the expression of Irisin/FNDC5 and semaphorin 3A in rats exposed to cigarette smoke extract.

In the current study, we investigated the impacts of 6 weeks of aerobic interval training (AIT) with selenium nanoparticles (SeNPs) on muscle, serum, and lung irisin (FNDC5) and Sema3A in rats exposed to cigarette smoke extract (CSE). To this end, 49 male Wistar rats (8 weeks old) were divided into seven groups: control, SeNPs (2.5 mg/kg b.w by oral gavage, 3 days/week, 6 weeks), AIT (49 min/day, 5 days/week for 6 weeks, interval), SeNPs + AIT, CSE (150 µL by IP injection, 1 day/week for 6 weeks), CSE + AIT, and CSE + SeNPs + AIT. The CSE group showed a significant reduction in irisin and Sema3A serum levels, as well as a decrease in FNDC5 and Sema3A gene expression in lung tissue (p < 0.05). A combined treatment (AIT with SeNPs) significantly increased the serum level and the expression of muscle and lung irisin (FNDC5) and Sema3A in CSE received groups (p < 0.05). There was a positive and significant correlation between muscle FNDC5 and lung FNDC5 in the CSE + SeNPs + AIT group (r = 0.92, p = 0.025). In addition, there was a positive and significant correlation between serum Sema3A and lung Sema3A of CSE + SeNPs + AIT group (r = 0.97, p = 0.004). Seemingly, performing aerobic exercises with the antioxidant and anti-inflammatory supplement nano-selenium in the model of lung damage (similar to COPD) can boost myokine irisin and Sema3A, especially in serum and lung tissue. These results displayed the paracrine/endocrine regulatory function of these myokines on other tissues. In other words, these interventions emphasized the creation of crosstalk between skeletal muscles and damaged lung, focusing on its recovery; however, further research is needed.

Effects of swimming exercise combined with silymarin and vitamin C supplementation on hepatic inflammation, oxidative stress, and histopathology in elderly rats with high-fat diet-induced liver damage.

OBJECTIVES: The aim of this study was to demonstrate that swimming exercise combined with silymarin and vitamin C supplementation improves hepatic inflammation, oxidative stress, and liver histopathology in elderly rats with high-fat diet-induced liver damage. METHODS: Forty elderly male Wistar rats were randomly assigned to five groups (n = 8 in each): a normal diet (control), a high-fat diet (HFD), HFD + silymarin and vitamin C supplementation (HFD+Sup), HFD + swimming exercise (HFD+Exe), and HFD+Sup+Exe group (HFD+Sup+Exe). The non-alcoholic fatty liver model was induced for 6 wk in the HFD groups. After 6 wk of consuming an HFD, a daily supplemental gavage was administered to rats as an intervention along with HFD in the supplement groups for 8 wk. Moreover, rats in the exercise groups were subjected to swimming exercise training 5 d/wk for the same period. RESULTS: The combination of swimming training and supplementation caused significant decreases in liver inflammatory biomarkers tumor necrosis factor-α and interleukin-1ß while increasing total antioxidant capacity and peroxisome proliferator-activated receptor α (P < 0.05). CONCLUSION: In elderly rats with liver injury caused by an HFD, the combination of exercise and silymarin with vitamin C supplementation effectively reduced oxidative stress, liver inflammation, fat accumulation, and regulated liver enzymes.

The effect of 24-hour sleep deprivation and anaerobic exercise on the expression of BAX, BCL2, BMAL1 and CCAR2 genes in peripheral blood mononuclear cells after L-arginine supplementation.

Sleep deprivation disrupt the circadian clock and exercise performance. Defective oxidative stress caused by sleep deprivation may affect the expression of genes involved in cell apoptosis. Since a number of studies have shown the anti-apoptotic effect of L-arginine, so the aim of this study was to evaluate the effect of eight weeks of L-arginine supplementation on the expression of brain and muscle ARNT-like protein 1 (BMAL1), cell cycle and apoptosis regulator 2 (CCAR2), and BAX and BCL2 genes during sleep deprivation and acute anaerobic exercise. Participants included 20 healthy men age 26-35 years, randomized into the L-arginine intervention group (n = 10) and a placebo control (n = 10). The running-based anaerobic sprint test (RAST) was used for anaerobic exercise. Intervention subjects took one 1000 mg L-arginine tablet daily for 8 weeks. The Real-Time PCR method was used to determine apoptosis gene expression in peripheral blood mononuclear cells (PBMCs). Acute anaerobic exercise and sleep deprivation both increased the expression of BAX and CCAR2 genes, and decreased the expression of BCL2 and BMAL1 genes (p < 0.05 for all). L-arginine supplementation increased the expression of BMAL1 and BCL2 genes and decreased the expression of BAX and CCAR2 genes relative to control (p < 0.05). L-Arginine controlled the increase in expression of BAX and CCAR2 genes and the decrease in expression of BCL2 and BMAL1 genes in response to sleep deprivation and acute anaerobic exercise (p < 0.05). Our results showed that 24-hour sleep deprivation and acute anaerobic exercise increased the expression of pro-apoptotic genes (BAX and CCAR2) and decreased the expression of anti-apoptotic genes (BCL2 and BMAL1), although the effect of sleep deprivation is greater. In this situation, L-arginine supplementation may balance the apoptotic state of peripheral blood mononuclear cells. However, any recommendation about this needs further research.

Swimming and L-arginine loaded chitosan nanoparticles ameliorates aging-induced neuron atrophy, autophagy marker LC3, GABA and BDNF-TrkB pathway in the spinal cord of rats.

Aging is associated with muscle atrophy, and erosion and destruction of neuronal pathways in the spinal cord. The study aim was to assess the effect of swimming training (Sw) and L-arginine loaded chitosan nanoparticles (LA-CNPs) on the sensory and motor neuron population, autophagy marker LC3, total oxidant status/total antioxidant capacity, behavioural test, GABA and BDNF-TrkB pathway in the spinal cord of aging rats. The rats were randomized to five groups: young (8-weeks) control (n = 7), old control (n = 7), old Sw (n = 7), old LA-CNPs (n = 7) and old Sw + LA-CNPs (n = 7). Groups under LA-CNPs supplementation received 500 mg/kg/day. Sw groups performed a swimming exercise programme 5 days per week for 6 weeks. Upon the completion of the interventions the rats were euthanized and the spinal cord was fixed and frozen for histological assessment, IHC, and gene expression analysis. The old group had more atrophy in the spinal cord with higher changes in LC3 as an indicator of autophagy in the spinal cord compared to the young group (p < 0.0001). The old Sw + LA-CNPs group increased (improved) spinal cord GABA (p = 0.0187), BDNF (p = 0.0003), TrkB (p < 0.0001) gene expression, decreased autophagy marker LC3 protein (p < 0.0001), nerve atrophy and jumping/licking latency (p < 0.0001), improved sciatic functional index score and total oxidant status/total antioxidant capacity compared to the old group (p < 0.0001). In conclusion, swimming and LA-CNPs seems to ameliorate aging-induced neuron atrophy, autophagy marker LC3, oxidant-antioxidant status, functional restoration, GABA and BDNF-TrkB pathway in the spinal cord of aging rats. Our study provides experimental evidence for a possible positive role of swimming and L-arginine loaded chitosan nanoparticles to decrease complications of aging.

Hepatoprotective effects of moderate-intensity interval training along with ginger juice in an old male rat model.

Aging is a natural process coupled with oxidative stress and chronic inflammation, gradually associated with losing organ function over time. Therefore, the objective of the current work was to peruse the protective effects of 8-week moderate-intensity interval training (MIIT) and ginger extract supplementation on some biomarkers of oxidative stress, inflammation, and lipid metabolism in the liver of elderly males Wistar rats (animal study with ethical code IR.BMSU.REC.1401.015). A total of thirty-two 22-month-aged male Wistar rats were randomly assigned to four groups: (1) control, (2) MIIT, (3) ginger, and (4) MIIT + ginger. After 8 weeks of treadmill training and ginger extract supplementation, the biochemical parameters (liver enzyme and lipid profile), inflammatory mediators (leucine-rich α-2 glycoprotein 1 (LRG1), tumor necrosis factor-alpha, and interleukin-6), pro-oxidant (malondialdehyde), antioxidant biomarkers (catalase, superoxide dismutase, total antioxidant capacity), some lipid metabolism regulators (carnitine palmitoyltransferase 1, adipose triglyceride lipase, acetyl-CoA carboxylase, CD36, and AMP-activated protein kinase), and liver histopathological changes were appraised. The acquired findings pointed out that MIIT combined with ginger extract appreciably diminished the serum levels of LRG1, liver enzymes, and lipid profile relative to the other groups after 8 weeks of intervention. Furthermore, ginger + MIIT caused a great improvement in the liver levels of antioxidant biomarkers, pro-oxidant, pro-inflammatory biomarkers, lipid metabolism regulators, and liver tissue impairment compared to the other groups. The findings suggested that MIIT + ginger was more effective in improving examined indices relative to the other groups.

Swimming exercise and nano-l-arginine supplementation improve oxidative capacity and some autophagy-related genes in the soleus muscle of aging rats.

The present research aims to evaluate the effect of swimming exercise and chitosan-coated l-arginine on mitochondrial oxidation, BCL2 Interacting Protein 3 (Bnip3), NIP-like protein × (Nix), B-cell lymphoma-extra-large (Bcl-xL) and autophagy-related protein light chain 3(LC3) expression in soleus muscle of aging rats. In this experimental research, 25 male Wistar rats were assigned into five groups randomly: young, old, old + Nano l-arginine (Nano L-a), old + exercise (Ex), and old + Nano l-arginine (Nano L-a) + exercise (Ex) (n = 5 in each). They performed a swimming exercise program five days a week for six weeks. To determine the relative strength for rats before and after performing these interventions, the 1repetition maximum (1RM) test was done as a pre and post-test. The exercise program started with 20 min and after four sessions, gradually increased to 60 min and this time was maintained until the completion of the training period. l-arginine coated with chitosan nanoparticles was given to the rats in the l-arginine-supplemented group via gavage at a dosage of 500 mg/kg/day, five days a week, for six weeks. Additionally, the rats in all groups were fed a normal diet (2.87 kcal/g and 15 % energy from fat). Upon the completion of the protocol implementation, the rats were sacrificed and the soleus muscle was fixed and frozen to determine hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), gene expression analysis, levels of reactive oxygen species (ROS), and total antioxidant capacity (TAC). The results from the present research indicated that swimming exercise and Nano l-arginine improve the strength and histology of muscle tissue in old rats (p < 0.05). Aging significantly increased the expression of Nix and Bnip3 (p < 0.05) and reduced the Bcl-xL gene expression (p < 0.05). The expression of LC3 protein also increased with aging (p < 0.05). Therapeutic interventions, such as combined treatment (old + Nano L-a + Ex) for old animals, reduced the amount of this protein in soleus muscle (p < 0.05). The ROS values also showed a significant reduction only in the old + Nano L-a + Ex group compared to the old group. Moreover, TAC values show a significant decrease in the old and old + Ex groups in comparison to the young group. The use of arginine supplement, especially in nano form, along with swimming exercise seems to reduce the oxidative damage to the elderly muscle tissue, which has a positive effect on the structure and function of the soleus muscle. Since these interventions only had a significant effect on LC3 protein, further studies with more diverse measurement methods for autophagy are suggested.

Swimming exercise with L-arginine coated nanoparticles supplementation upregulated HAND2 and TBX5 expression in the cardiomyocytes of aging male rats.

We investigated possible cardioprotective mechanisms of L-arginine coated nanoparticles (L-ACN) combined with swimming exercise (SE) in aging male rats considering heart and neural crest derivatives-expressed protein 2 (HAND2) and t-box transcription factor 5 (TBX5). Thirty-five male Wistar rats were randomly assigned into five groups: young, old, old + L-ACN, old + SE, and old + L-ACN + SE (n = 7 in each). L-arginine coated with chitosan nanoparticles was given to L-ACN groups via gavage at 500 mg/kg/day. SE groups performed a swimming exercise program 5 days per week for 6 weeks. The exercise program started with 20 min, gradually increasing to 60 min after four sessions, which was then constant until the completion of the training period. After the protocol completion, the rats were sacrificed, and the heart was fixed and frozen to carry out histological, immunohistochemistry (IHC), and gene expression analyses. The expression of HAND2 protein, HAND2 mRNA, and TBX5 mRNA of the heart tissue was significantly higher in the young group than in all older groups (P < 0.05). The old + L-ACN, old + SE, and old + L-ACN + SE groups showed a significant increase in these factors compared to the old group (P < 0.05). Nano-L-arginine supplement, along with swimming exercises, seems to have cardioprotective potential and improve cardiac function in old age by strengthening cardiomyocyte signaling, especially HAND2 and TBX5. However, more research is required, particularly on human samples.