Lipoic acid inhibits cognitive impairment induced by multiple cell phones in young male rats: role of Sirt1 and Atg7 pathway.

The utilization of digital technology has grown rapidly in the past three decades. With this rapid increase, cell phones emit electromagnetic radiation; that is why electromagnetic field (EMF) has become a substantial new pollution source in modern civilization, mainly having adverse effects on the brain. While such a topic attracted many researchers' scopes, there are still minimal discoveries made regarding chronic exposure to EMF. The extensive use of cell phones may affect children's cognition even indirectly if parents and guardians used their phones repeatedly near them. This study aims to investigate possible lipoic acid (LA) effects on cognitive functions and hippocampal structure in young male rats exposed to electromagnetic fields (EMF) emitted from multiple cell phones. Forty young male Wistar rats were randomly allocated into three groups: control, multiple cell phones-exposed and lipoic acid-treated rats. By the end of the experimental period, the Morris water maze was used as a cognitive test. The rats were sacrificed for the collection of serum and hippocampal tissue. These serum samples were then utilized for assessment of Liver function tests. The level ofglutamate, acetylcholine (Ach) and malondialdehyde (MDA) was estimated, in addition to evaluating the expression of autophagy-related protein-7 (Atg7) and Sirt1 genes. The left hippocampal specimens were used for histopathological studies. Results showed that multiple cell phone-exposed rats exhibited shorter latency time to reach the platform by the fifth day of training; additionally, there was a reduction in consolidation of spatial long-term memory. Correspondingly, there was an elevation of hippocampal Ach, glutamate, and MDA levels; accompanied by up-regulation of hippocampal Sirt1 and Atg7 gene expression. Compared to the EMF-exposed group, LA administration improved both learning and memory, this was proved by the significant decline in hippocampal MDA and Ach levels, the higher hippocampal glutamate, the downregulated hippocampal Sirt1 gene expression and the upregulated Atg7 gene expression. In conclusion, EMF exposure could enhance learning ability; however, it interfered with long-term memory consolidation shown by higher hippocampal Ach levels. Lipoic acid treatment improved both learning and memory by enhancing autophagy and hippocampal glutamate level and by the reduced Ach levels and Sirt1 gene expression.

Can Intranasal Administration of Adipose-Derived Stem Cells Reach and Affect the Histological Structure of Distant Organs of Aged Wistar Rat?

Introduction: Stem cell therapy is a highly promising strategy in various degenerative diseases. Intranasal administration of stem cells could be considered as a non-invasive treatment option. However, there is great debate concerning the ability of stem cells to reach distant organs. It is also unclear in such a case if they can alleviate age-related structural changes in these organs. Aim: The aim of this study is to evaluate the ability of intranasal administration of adipose-derived stem cells (ADSCs) to reach distant organs of rats at different time intervals and to investigate their effects on age-related structural changes in these organs. Materials and Methods: Forty-nine female Wistar rats were used in this study, seven of which were adults (6-month-old) and 42 were aged (2-year-old). Rats were divided into three-groups: Group-I (adult control), Group-II (aged), and Group-III (aged ADSCs treated). Rats of Groups I and II were sacrificed after 15 days from the beginning of the experiment. Rats of Group III were treated with intranasal ADSCs and were sacrificed after 2-h, 1-day, 3-day, 5-day, and 15-day. Heart, liver, kidney, and spleen specimens were collected and processed for H and E, CD105 immunohistochemistry, and immunofluorescent techniques. Morphometric study and statistical analysis were performed. Results: ADSCs appeared in all organs examined after 2-h of intranasal administration. Their maximum presence was detected after 3-day of administration, after which their immunofluorescence gradually decreased and nearly disappeared from these organs by the 15th day. Improvement of some age-related deterioration in the structure of the kidney and liver occurred at day 5 after intranasal administration. Conclusions: ADSCs effectively reached the heart, liver, kidney, and spleen after intranasal administration. ADSCs ameliorated some age-related changes in these organs.

Sitagliptin's renoprotective effect in a diabetic nephropathy model in rats: The potential role of PI3K/AKT pathway.

Management of diabetic nephropathy (DN) is far from satisfactory. There is a rising role of the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in the pathogenesis of DN. This study aimed at investigating the renoprotective effects of PI3K/AKT pathway via sitagliptin in a rat model of DN. Thirty-two male Wistar rats were divided into four groups (eight rats each): (I) control, (II) sitagliptin, (III) DN, and (IV) DN + sitagliptin. Fasting blood glucose (FBG), kidney index, and kidney function tests in both blood and urine were measured. The levels of superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß) and gene expressions of PI3K, pPI3K, AKT, and pAKT in renal tissue were detected. Renal histopathological and immunohistochemical studies were evaluated. DN + sitagliptin group showed significant decrease in FBG and kidney index, improvement in kidney function tests, and a decrease in levels of TNF-α and TGF-ß in renal tissues compared with DN group. This was associated with significant increase in SOD and gene expressions of PI3K and AKT and their phosphorylated active forms in renal tissue in DN + sitagliptin group compared with DN group. Moreover, DN + sitagliptin group showed apparent decrease in amount of collagen fibers and expression of alpha-smooth muscle actin (α-SMA) compared with DN group. This work shows that sitagliptin improved renal functions and histopathological changes, impeded inflammation, and oxidative stress and upregulated PI3K/AKT pathway which highlights its renoprotective effects in a rat model of DN.

Involvement of TLR4/ CXCL9/ PREX-2 pathway in the development of hepatocellular carcinoma (HCC) and the promising role of early administration of lactobacillus plantarum in Wistar rats.

BACKGROUND AND AIM: Improvement of gut microbiota may help in preventing the progression of cirrhosis. We supposed that Lactobacillus Plantarum (L. Plantarum) protects the cirrhotic liver through suppression of TLR4/ CXCL9/ PREX-2. METHODOLOGY: Rats were divided into two groups. Group I, lasts for six weeks and Group II lasts for 12 weeks. Each group was subdivided into: naïve, Lactobacillus Plantarum (L. Plantarum), thioacetamide (TAA) and TAA + L. Plantarum. Liver function tests, α fetoprotein (AFP) levels, CXCL9, PREX-2 and TLR4 expression were assessed. Histological studies were performed. RESULTS: TAA induced significant deterioration in liver functions and increased AFP. There was periportal cirrhosis, vacuolated hepatocytes, decrease hepatocyte parrafin-1 (hep par-1) expression, increase proliferating cell nuclear antigen (PCNA) positive nuclei and cytokeratin AE1/AE3. The PCR results showed significant increase in TLR4, CXCL9 and PREX-2 expression. Early administration of L. Plantarum significantly decreased the expression of TLR4, CXCL9 and PREX-2 together with improvement in liver function and prevented the pathological changes. CONCLUSIONS: The cirrhotic complications induced by TAA are through activation of TLR4/ CXCL9/ PREX-2 pathway and could be prevented by the early administration of L. Plantarum.

Zoledronic acid prevents the hepatic changes associated with high fat diet in rats; the potential role of mevalonic acid pathway in nonalcoholic steatohepatitis.

The role of hepatic free cholesterol (FC) in nonalcoholic steatohepatitis (NASH) is raised up and the intervention with cholesterol synthesis will be a potential therapeutic target. This study investigated the hepatoprotective effect of mevalonic acid pathway inhibition by Zoledronic acid (ZA) on the hepatic changes associated with high fat diet (HFD) in rats.Thirty two male Wistar rats were used. They were divided into 2 groups: (I) control naïve (II) NASH: induced by HFD for 12 weeks, this group is subdivided into (A) NASH untreated (B)NASH + ZA (50ug/kg/week) i.p. for 12 weeks (C) NASH + ZA (100µg/kg/week) i.p. for 12 weeks. Portal pressure (PP), liver enzymes AST and ALT, serum glucose, lipid profile, hepatic levels of tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), FC and triglyceride (TG), histopathological changes and expression of both hepatic alpha smooth muscle actin (α-SMA) and Caspase-3 were measured. ZA significantly prevented portal hypertension, worsening in liver function, and dyslipidemia. The hepatic levels of TNF-α, VEGF, FC and TG were significantly decreased in comparison to NASH untreated group. ZA hindered the histopathological changes induced by HFD. ZA inhibited the expression of hepatic α-SMA and Caspase-3 with significant difference favor the high dose intervention. ZA in a dose related manner prevents the hepatic pathological effects of chronic HFD ingestion in rats. This may be largely mediated by its ability to reduce TNF-α and hepatic FC.

Comparative Study on Acellular Dermal Graft Versus Propylene Mesh Both Either Loaded or Unloaded with BM-MSCs in Healing of Skull Bone Defect in Rats: Histological and Immunohistochemical Study.

Bone defect occurs as a consequence of many conditions. Diseased bones don't heal properly and defects in face area need proper bone reconstruction to avoid psychological and social problems. Tissue engineering is an emerging new modality of treatment. We thought to study different methods to fill skull bone defect in rats in order to find the most safe and effective method. So, this study was designed to evaluate the efficacy of acellular dermal graft (ADM) versus propylene mesh both either loaded or unloaded with bone marrow derived mesenchymal stem cells (BM-MSCs) in healing of skull bone defect of a 5 mm diameter. The study included 36 adult male Wistar albino rats that were divided into three groups according to the way of filling skull bone defect. Group I: Ia (sham control), Ib (negative control). Group II: IIa (unseeded propylene), IIb (seeded propylene) and Group III: IIIa (unseeded ADM), IIIb (seeded ADM). The trephine operation was done on the left parietal bone. Specimens were collected four weeks postoperative and processed for H&E, osteopontin immunohistochemistry and scanning electron microscope. Morphometric and statistical analysis were also performed. After studying the results of the experiment, we found that propylene mesh and ADM were suitable scaffolds that could support new bone formation in clavarial bone defect. Healing of skull bone defect was better in rats that received seeded scaffolds more than rats with unseeded scaffolds. The seeded ADM showed significant increase in bone forming activity as confirmed by histomorphometric and statistical results.

Theophylline, an old drug with multi-faceted effects: Its potential benefits in immunological liver injury in rats.

AIM: A low dose of theophylline enhances histone deacetylase activity leading to inhibition of proinflammatory transcription, and inhibits lung fibroblast proliferation. The present work investigated the effect of lowdose theophylline on biochemical and histological pictures of liver tissues in rats with immunological hepatic injury induced by concanavalin A (Con A). MAIN METHODS: Ratswere assigned to control vehicle,model (Con A) and theophylline groups. Half of the animals in each group were sacrificed at the end of the 4th week and the other half were sacrificed at the end of the 8th week. KEY FINDINGS: There was a time-dependent increase in the liver injury parameters by the end of the 4th and 8th weeks in the Con A treated group. Theophylline (20 mg/kg/day), produced a significant decrease in serum liver enzymes (ALT, AST), serum interferon gamma (IFN-γ) levels and the hepatic transforming growth factor-ß (TGF-ß) level. A significant decrease in liver tissue hydroxyproline content together with reduction in portal hypertension at the end of the 8th week was detected compared to the Con A group. Theophylline treated rats exhibited a significant decrease in hepatic vacuolation, apoptosis, leucocyte infiltration, and accumulation of collagen fibers in comparison to the Con A group. In addition, significant decreases in the area percentage of fibrosis and the area percentage of caspase +ve cells were reported compared to the Con A group. SIGNIFICANCE: Theophylline effectively reduced the inflammation of liver tissues and alleviated the liver damage by decreasing IFN-γ and TGF-ß in liver tissues of rats with immunological hepatic injury.