The SIRT3/GSK-3ß/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle insulin resistance in old male rat offspring.

Maternal hypoxia is strongly linked to insulin resistance (IR) in adult offspring, and altered insulin signaling for muscle glucose uptake is thought to play a central role. However, whether the SIRT3/GSK-3ß/GLUT4 axis is involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring has not been investigated. Maternal hypoxia was established from Days 5 to 21 of pregnancy by continuous infusion of nitrogen and air. The biochemical parameters and levels of key insulin signaling molecules of old male rat offspring were determined through a series of experiments. Compared to the control (Ctrl) old male rat offspring group, the hypoxic (HY) group exhibited elevated fasting blood glucose (FBG) (∼30%), fasting blood insulin (FBI) (∼35%), total triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), as well as results showing impairment in the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) revealed impaired cellular structures and mitochondria in the longitudinal sections of skeletal muscle from HY group mice, which might be associated with decreased SIRT3 expression. Furthermore, the expression of insulin signaling molecules, such as GSK-3ß and GLUT4, was also altered. In conclusion, the present results indicate that the SIRT3/GSK-3ß/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring.

Dapagliflozin dampens liver fibrosis induced by common bile duct ligation in rats associated with the augmentation of the hepatic Sirt1/AMPK/PGC1α/FoxO1 axis.

Liver fibrosis is considered an epidemic health problem due to different insults that lead to death. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is one of the newer anti-diabetic drugs used to manage type 2 diabetes mellitus (T2DM). DAPA exerted beneficial effects in many human and rat models due to its antioxidant, anti-inflammatory and antifibrotic activities. AIM: Due to previously reported capabilities related to DAPA, we designed this study to clarify the beneficial role of DAPA in liver fibrosis triggered by common bile duct ligation (CBL) in male rats. METHODS: For 14 or 28 days after CBL procedures, DAPA was administered to the rats orally at a dose of 10 mg/kg once daily. The effects of DAPA were evaluated by assaying liver enzymes, hepatic oxidant/antioxidant parameters, serum levels of tumor necrotic factor alpha (TNF-α), and AMP-activated protein kinase (AMPK). In addition, we measured the hepatic expression of fibrosis regulator-related genes along with evaluating liver histological changes. KEY FINDINGS: DAPA successfully decreased hepatic enzymes and malondialdehyde levels, increased superoxide dismutase activity, elevated catalase levels, decreased serum levels of TNF-α, elevated serum levels of AMPK, decreased liver hydroxyproline content, upregulated Sirt1/PGC1α/FoxO1 liver gene expressions, down-regulated fibronectin-1 (Fn-1), collagen-1 genes in liver tissues, and improved the damaged liver tissues. Deteriorated biochemical parameters and histological liver insults associated with CBL were more pronounced after 28 days, but DAPA administration for 14 and 28 days showed significant improvement in most parameters and reflected positively in the histological structures of the liver. SIGNIFICANCE: The significance of this study lies in the observation that DAPA mitigated CBL-induced liver fibrosis in rats, most likely due to its antioxidant, anti-inflammatory, and antifibrotic effects. These results suggest that DAPA's beneficial impact on liver fibrosis might be attributed to its interaction with the Sirt1/AMPK/PGC1α/FoxO1 pathway, indicating a potential mechanistic action for future exploration.

Analysis of the finasteride treatment and its withdrawal in the rat hypothalamus and hippocampus at whole-transcriptome level.

PURPOSE: As reported in patients treated for androgenetic alopecia with finasteride (i.e., a blocker of the enzyme 5 alpha-reductase) and in an animal model, side effects affecting sexual, psychiatric, neurological, and physical domains, may occur during the treatment and persist with drug suspension. The etiopathogenesis of these side effects has been poorly explored. Therefore, we performed a genome-wide analysis of finasteride effects in the brain of adult male rat. METHODS: Animals were treated (i.e., for 20 days) with finasteride (1mg/rat/day). 24 h after the last treatment and 1 month after drug suspension, RNA sequencing analysis was performed in hypothalamus and hippocampus. Data were analyzed by differential expression analysis and Gene-Set Enrichment Analyses (GSEA). RESULTS: Data obtained after finasteride treatment showed that 186 genes (i.e., 171 up- and 15 downregulated) and 19 (i.e., 17 up- and 2 downregulated) were differentially expressed in the hypothalamus and hippocampus, respectively. Differential expression analysis at the drug withdrawal failed to identify dysregulated genes. Several gene-sets were enriched in these brain areas at both time points. CONCLUSION: Some of the genes reported to be differentially expressed (i.e., TTR, DIO2, CLDN1, CLDN2, SLC4A5, KCNE2, CROT, HCRT, MARCKSL1, VGF, IRF2BPL) and GSEA, suggest a potential link with specific side effects previously observed in patients and in the animal model, such as depression, anxiety, disturbance in memory and attention, and sleep disturbance. These data may provide an important background for future experiments aimed at confirming the pathological role of these genes.

Protective efficacy of Nerium oleander extract on spermatogenesis in streptozotocin-induced diabetic rats.

Men with diabetes frequently experience spermatogenic dysfunction, which is the most significant sign that diabetes has harmed their ability to reproduce. The effect of various doses of the hydro-alcoholic extract of Nerium oleander leaves on the pituitary-gonadal axis, sperm motility and number, antioxidant system, changes in testicular tissue structure, and spermatogenesis in healthy and diabetic rats has been examined in the current study. Eighty male rats that had been streptozotocin-induced diabetic and healthy were divided into eight groups: (1) control, (2) Nerium (50 mg/kg), (3) Nerium (100 mg/kg), (4) Nerium (200 mg/kg), (5) DM (6) DM+Nerium (50 mg/kg), (7) DM+Nerium (100 mg/kg) and (8) DM+Nerium (200 mg/kg) and were administered orally for 48 days consecutive. Following the studies, analysis of the testicular tissues' antioxidant capacity as well as sperm parameters, Johnsen's scoring and morphometric evaluation, histology, biochemical and stereology studies were performed.The outcomes showed that Nerium 50 and 100 mg/kg considerably enhanced the testicular morphology, sperm parameters, and reproductive organs to varying degrees in diabetic rats. After Nerium 50 mg/kg administration, glutathione peroxidase (GPX) and catalase (CAT) levels in the testicular tissue were increased whereas malondialdehyde (MDA) levels were markedly decreased. Nerium may help protect against diabetic-induced spermatogenic dysfunction in male rats by enhancing the activities of antioxidant enzymes in lower dosages.

Morphometric, biochemical and histopathological effects of sofosbuvir (sovaldi) on testes of adult male albino rats.

Sofosbuvir treatment regimens for chronic HCV infection have recently been linked to extra hepatic side effects. This study aimed to show how sofosbuvir affected the adult male albino rat testis. Forty adult male albino rats were used. The rats were equally split into two main groups (I and II), then each group subdivided into two subgroups (A and B). Each rat in group I (control) received 0.5 ml of distilled water every day for four weeks. Each rat in group II (sofosbuvir-treated) received 0.5 ml of distilled water containing 7.2 mg of sofosbuvir every day for four weeks. After four weeks (subgroups IA and IIA) and eight weeks (subgroups IB and IIB) of treatment, the rats were sacrificed. Histological, biochemical, and morphometric studies on the testes were conducted. The data were analyzed. Examination of testes of sovaldi treated group revealed histopathological changes. Biochemical and morphometric analysis showed reduced levels of reduced glutathione and seminiferous tubule epithelial height respectively. Following a 4-week drug withdrawal period, the testes only partially recovered. We concluded that sofosbuvir induced deteriorating changes in the adult male albino rats' testes. These changes were proved by histological and biochemical studies. These changes were incompletely reversible after cession of treatment. Researches investigating the effect of adding drugs that have antioxidant properties during sofosbuvir therapy are recommended.

Perinatal exposure to bisphenol A impairs cognitive function via the gamma-aminobutyric acid signaling pathway in male rat offspring.

Bisphenol A (BPA) is a common synthetic endocrine disruptor that can be utilized in the fabrication of materials such as polycarbonates and epoxy resins. Numerous studies have linked BPA to learning and memory problems, although the precise mechanism remains unknown. Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the vertebrate central nervous system, and it is intimately related to learning and memory. This study aims to evaluate whether altered cognitive behavior involves the GABA signaling pathway in male offspring of rats exposed to BPA during the prenatal and early postnatal periods. Pregnant rats were orally given BPA (0, 0.04, 0.4, and 4 mg/kg body weight (BW)/day) from the first day of pregnancy to the 21st day of breastfeeding. Three-week-old male rat offspring were selected for an open-field experiment and a new object recognition experiment to evaluate the effect of BPA exposure on cognitive behavior. Furthermore, the role of GABA signaling markers in the cognition affected by BPA was investigated at the molecular level using western blotting and real-time polymerase chain reaction (RT-PCR). The research demonstrated that BPA exposure impacted the behavior and memory of male rat offspring and elevated the expression of glutamic acid decarboxylase 67 (GAD67), GABA type A receptors subunit (GABAARα1), and GABA vesicle transporter (VGAT) in the hippocampus while decreasing the expression levels of GABA transaminase (GABA-T) and GABA transporter 1 (GAT-1). These findings indicate that the alteration in the expression of GABA signaling molecules may be one of the molecular mechanisms by which perinatal exposure to BPA leads to decreased learning and memory in male rat offspring.

Enterotype-Dependent Probiotic-Mediated Changes in the Male Rat Intestinal Microbiome In Vivo and In Vitro.

Beneficial properties of lactic acid bacteria have been known long ago, but particular interest in probiotics has arisen in the last two decades due to the understanding of the important role of intestinal microflora in human life. Thus, the ability of probiotics to support healthy homeostasis of gut microbiomes has received particular attention. Here, we evaluated the effect of a probiotic consisting of Bifidobacterium longum and Lacticaseibacillus paracasei on the gut microbiome of male rats, assessed their persistence in the fecal biota, and compared probiotic-mediated changes in vitro and in vivo. As expected, microbiomes of two enterotypes were identified in the feces of 21 animals, and it turned out that even a single dose of the probiotic altered the microbial composition. Upon repeated administration, the E1 biota temporarily acquired properties of the E2 type. Being highly sensitive to the intervention of probiotic bacteria at the phylum and genus levels, the fecal microbiomes retained the identity of their enterotypes when transferred to a medium optimized for gut bacteria. For the E2 biota, even similarities between probiotic-mediated reactions in vitro and in vivo were detected. Therefore, fecal-derived microbial communities are proposed as model consortia to optimize the response of resident bacteria to various agents.

[Detection methods and evaluation indexes of sexual motivation in male rats: An update].

Sexual motivation refers to the intensity of willingness to have sex with or near a potential partner and is important for sexual health. At present, low sexual desire has become an increasingly prominent social problem, and there are no unified standards for its detection and evaluation. In this paper, we systematically sorted out the commonly used methods for detecting sexual motivation in male rats, including the three major categories of male-female mating, competitive selection and task acquisition, and discussed the relevant evaluation indexes and the advantages and disadvantages of various methods. We also explored the nature of sexual motivation, elaborated sexual contact behavior as a direct manifestation of sexual motivation, and proposed focusing relevant studies on contact behaviors and differentiating sexual proximity from social proximity.

THE POTENTIAL RENOPROTECTIVE EFFECT OF TILIANIN IN RENAL ISCHEMIA REPERFUSION INJURY IN MALE RAT MODEL.

OBJECTIVE: The aim: To determine whether Tilianin (TIL) may have Nephroprotective effects on bilateral renal IRI in rats by analyzing kidney function biomarkers U and Cr, inflammatory cytokines like TNF α and IL-1ß, antioxidant marker total anti-oxidant Capacity (TAC), anti-apoptotic markers caspase-3, and histopathological scores. PATIENTS AND METHODS: Materials and methods: 20 rats divided into even 4 groups as: Sham group: Rats underwent median laparotomies without having their ischemia induced. Control group: Rats had bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion. Vehicle group: 30 minutes prior to the onset of ischemia, rats were given a pretreatment of corn oil and DMSO. Tilianin treated group: Rats administered Tilianin 5 mg/kg for 30 min prior to ischemia induction, then IRI. RESULTS: Results: The study found that the serum levels of TNF, IL-1, caspase-3, urea and creatinine, as well as TNF and creatinine in the Tilianin group were significantly lower than those of the control and vehicle groups. On the other hand, it revealed that TAC levels are remarkably higher in the Tilianin group than they are in the control and vehicle groups. CONCLUSION: Conclusions: This study concluded that Tilianin have a Nephroprotective effect via multiple impacts as anti-inflammatory, anti-apoptotic, and anti-oxidant agents.

The pro-convulsant effects of diazinon low dose in male rats under amygdala kindling.

Organophosphates can damage the brain in systemic intoxication. In this study, the effects of a minimum toxic dose (MTD) of diazinon (DZ) on amygdala afterdischarge threshold (ADT), kindling acquisition and kindled seizure parameters were evaluated. Intact male rats were stereotactically implanted with a tripolar and two monopolar electrodes in the amygdala and dura respectively. After recovery, animals received daily either, olive oil (control), 15 or 30 mg/kg (MTD) of DZ intraperitoneally, and ADT, afterdischarge duration (ADD) at each stage (S1 to S5) of kindling and number of trials for kindling acquisition were determined daily. Also, the effect of DZ on stage 4 latency (S4L), ADD, stage 5 duration (S5D) and the activity of the red blood cholinesterase (ChE) were evaluated. The ADT was lower and the ADD was longer significantly in DZ treated group in comparison to control (p < 0.01) and the number of trials to reach each stage of kindling acquisition was reduced (p < 0.001). The total amount of ADDs during the kindling procedure increased significantly 5 days after DZ treatment. While the S4L was reduced, the S5D increased significantly after DZ treatment. The ChE activity was inhibited significantly after 20 min of DZ treatment and continued till 24 h (p < 0.01). Data indicate that even half of the MTD of DZ could increase the sensitivity and excitability of the CNS to the epileptic activity at least via reduction of stimulation threshold and AD prolongation. Furthermore, repeated exposure to the low concentrations of organophosphates may be pro-convulsant and should be restricted.