Peroxisome proliferator-activated receptor gamma (PPAR-γ) is ubiquitously expressed in testicular tissue and plays a crucial role in regulating various physiological processes. Pioglitazone (PIO) is one of the PPAR-γ agonists, having anti-oxidant and anti-inflammatory effects. Patients on gentamycin treatment may undergo serious side effects such as testicular damage. To the best of our knowledge, this was the first study to investigate the possible protective anti-inflammatory and anti-apoptotic effects of PIO on gentamycin-induced testicular damage. Fifty adult male Wistar albino rats included in the study as the control group (CTL) received normal saline; a gentamycin-induced testicular damage group (GM) received gentamycin (100 mg/kg); PIO5, PIO10, PIO20 groups received PIO at a dose of 5, 10, and 20 mg/ kg, respectively, for 21 days, and gentamycin was started at day 15 of the experiment for 6 days. The parameters of spermatozoa and histopathological alterations in the testes were significantly improved in the PIO20 group. Moreover, MDA levels, inflammatory mediators, and apoptotic Bax expression were decreased. The activity of glutathione peroxidase, catalase, total antioxidant capacity, and anti-apoptotic Bcl-2 genes expression were increased. It was concluded that PIO20 could protect against gentamycin-induced testicular damage in Wistar rats through its anti-oxidant, anti-inflammatory, and antiapoptotic effects.

The prevalence of obesity has risen in the last decades, and it has caused massive health burdens on people’s health, especially metabolic and cardiovascular issues. The risk of vitamin D insufficiency is increased by obesity, because adipose tissue alters both the requirements for and bioavailability of vitamin D. Exercise training is acknowledged as having a significant and long-term influence on body weight control; the favorable impact of exercise on obesity and obesity-related co-morbidities has been demonstrated via various mechanisms. The current work illustrated the effects of vitamin D supplementation and exercise on obesity induced by a high-fat diet (HFD) and hepatic steatosis in rats and explored how fatty acid transport protein-4 (FATP4) and Toll-like receptor-4 antibodies (TLR4) might be contributing factors to obesity and related hepatic steatosis. Thirty male albino rats were divided into five groups: group 1 was fed a normal-fat diet, group 2 was fed an HFD, group 3 was fed an HFD and given vitamin D supplementation, group 4 was fed an HFD and kept on exercise, and group 5 was fed an HFD, given vitamin D, and kept on exercise. The serum lipid profile adipokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were analyzed, and the pathological changes in adipose and liver tissues were examined. In addition, the messenger–ribonucleic acid (mRNA) expression of FATP4 and immunohistochemical expression of TLR4 in adipose and liver tissues were evaluated. Vitamin D supplementation and exercise improved HFD-induced weight gain and attenuated hepatic steatosis, along with improving the serum lipid profile, degree of inflammation, and serum adipokine levels. The expression of FATP4 and TLR4 in both adipose tissue and the liver was downregulated; it was noteworthy that the group that received vitamin D and was kept on exercise showed also improvement in the histopathological picture of this group. According to the findings of this research, the protective effect of vitamin D and exercise against obesity and HFD-induced hepatic steatosis is associated with the downregulation of FATP4 and TLR4, as well as a reduction in inflammation.

Background/Objectives: One of the most abundant and growing neurodevelopmental disorders in recent decades is attention deficit hyperactivity disorder (ADHD). Many trials have been performed on using drugs for the improvement of ADHD signs. This study aimed to detect the possible interaction of naringin with Wnt/β-catenin signaling and its putative anti-inflammatory and protective effects in the mouse ADHD model based on bioinformatic, behavioral, and molecular investigations. Furthermore, molecular docking was applied to investigate possible interactions with the GSK-3β and HSP90 proteins. Methods: Male Swiss albino mice were divided into four groups, a normal control group, monosodium glutamate (SGL) control, SGL + naringin 50 mg/kg, and SGL + naringin 100 mg/kg. The psychomotor activity of the mice was assessed using the self-grooming test, rope crawling test, and attentional set-shifting task (ASST). In addition, biochemical analyses were performed using brain samples. Results: The results of the SGL group showed prolonged grooming time (2.47-folds), a lower percentage of mice with successful crawling on the rope (only 16.6%), and a higher number of trials for compound discrimination testing in the ASST (12.83 ± 2.04 trials versus 5.5 ± 1.88 trials in the normal group). Treatment with naringin (50 or 100 mg per kg) produced significant shortening in the grooming time (31% and 27% reductions), as well as a higher percentage of mice succeeding in crawling with the rope (50% and 83%, respectively). Moreover, the ELISA assays indicated decreased dopamine levels (0.36-fold) and increased TNF-α (2.85-fold) in the SGL control group compared to the normal mice, but an improvement in dopamine level was observed in the naringin (50 or 100 mg per kg)-treated groups (1.58-fold and 1.97-fold). Similarly, the PCR test showed significant declines in the expression of the Wnt (0.36), and β-catenin (0.33) genes, but increased caspase-3 (3.54-fold) and BAX (5.36-fold) genes in the SGL group; all these parameters were improved in the naringin 50 or 100 mg/kg groups. Furthermore, molecular docking indicated possible inhibition for HSP90 and GSK-3β. Conclusions: Overall, we can conclude that naringin is a promising agent for alleviating ADHD symptoms, and further investigations are required to elucidate its mechanism of action.

Background: Pulmonary Fibrosis is a chronic lung disease characterized by scar formation and respiratory insufficiency. Metformin is an antidiabetic drug that has recently been shown to prevent lung fibrosis via NADPH oxidase-4 suppression. Flaxseed oil has been shown to be a potent antioxidant that attenuates oxidative damage by inhibition of lipid peroxidation and the proinflammatory cytokine production of IL-6 and TNF-alpha. Aim: To investigate whether metformin and/or flaxseed oil could protect against bleomycin-induced pulmonary fibrosis and if this protection is mediated by inhibiting NOX-4 signaling pathway and the synthesis and release of inflammatory and oxidative stress markers. Material and Methods: Fifty adult male rats were randomized into 5 groups/10 rats each.Pulmonary fibrosis was induced by Bleomycin, delivered intratracheally at a concentration of 1.5mg/kg body weight once in group PF, MET, Flax and combined MET& Flax. Both metformin and Flaxseed oil were administered orally for 21 day after induction of PF. Withdrawal of blood samples for chemical and spectral assay of antioxidant markers was done. Histopathology and assessment of inflammatory and fibrotic markers and PCR expression of NOX4 gene were done. Results: There was a significant reduction in inflammatory cell count, histopathological score of inflammation and fibrosis in the three treatment groups. Also there was marked improvement in inflammatory (IL-6, TNF-a) and fibrotic markers (TGF-B and Col-1) in metformin group rather than flaxseed and combined group.Nox4 gene expression was significantly reduced in metformin treated group rather than other 2 groups

Introduction: While oxaliplatin (OXL) is an effective cancer chemotherapy, OXL-based therapy's practical usefulness is limited by its adverse effects, which include peripheral neuropathy (PN).Objective: to assess the potential underlying processes and the protective impact of metrnl in PN caused by OXL. Materials and Methods: There were three groups of thirty adult male albino rats: control, OXL and OXL+Metrnl groups (10/group). Electromyography (EMG) and nerve conduction velocity (NCV) were applied to rats, together with behavioral testing for pain and sensory abnormalities. The expression of several genes was evaluated in the sciatic nerve, including tissue MDA, (SOD), TNF-α, interleukin (IL)-6, IL-10, caspase-3, BDNF, nuclear factor E2‐related factor 2 (Nrf2), and homo-oxygenase 1 (HO-1). Additionally, histopathological evaluations of the gastrocnemius and sciatic nerve were carried out. Results The OXL group exhibited mechanical and cold allodynia, as well as significantly higher levels of MDA, TNF-α, IL-6, and caspase-3 than the control group. It also significantly reduced NCV, EMG recordings, IL-10, as well as down-regulating BDNF, Nrf2 and HO-1 gene expression in the sciatic nerve. OXL-induced PN changes were significantly ameliorated in the OXL+Metrnl groups. Conclusion: Metrnl has valuable protective effects on OXL-induced PN via anti-oxidant, anti-inflammatory, inhibition of apoptosis and neurotrophic effects in addition to up-regulation of Nrf2 and HO-1 gene expressions.

Introduction: Cognitive deficits and aging were evoked by D-galactose (D-gal). Fasudil (Fsd) slows the start and progress of neurodegenerative illnesses.Objective: to illustrate the neuroprotective effect of Fsd in D-gal induced cognitive deficits and the underling mechanisms involvedMaterial & methods: Thirty Wister albino male rats divided into control, D-gal, D-gal+Fsd groups. Rats were subjected to MWM, NOR and EPM tests then rats were sacrificed and MDA, catalase, TNF-α, IL-6 hippocampal gene expression of BDNF, SIRT1 and NF-kB were assessed. Histopathological and immunoreaction for caspase-3 and GFAP were done. Results: D-gal revealed cognitive impairment, with substantial elevation of MDA, TNF-α, IL-6 and NF-kB gene expression and significant reduction of catalase, SIRT1 and BDNF gene expression of D-gal with upregulation of caspase-3 and GFAP immunoreaction in hippocampus. Fsd dramatically improved D-gal induced changes.Conclusion: Fsd alleviated D-gal induced cognitive deficits by anti-oxidant, anti-inflammatory, anti-apoptotic mechanisms in addition to up-regulation of Sirt1 and BDNF gene expression and improving gliosis.