Esrafil Mansouri

Background: Nowadays, the use of over-the-counter drugs such as acetaminophen (APAP) may cause severe liver injury, which can occur not only in high doses but also in therapeutic doses due to nutritional deficiency, alcoholism, or using cytochrome p450 inducers. Objectives: In this study, the protective effect of epicatechin (EPC) was evaluated against APAP-induced hepatotoxicity to find an effective and inexpensive therapy. Methods: The animals were divided into preventive and therapeutic groups. In the preventive study, the animals received EPC (25, 50, and 100 mg/kg/day) for five days, and the last dose was administered 1 hour before APAP (400 mg/kg). In the therapeutic groups, the animals received EPC just before and 2 hours after the APAP injection. All the animals were killed, and blood and liver samples were taken for further analysis. The liver pathology, enzymes, and oxidant, antioxidant, inflammatory, and anti-inflammatory factors were evaluated. Results: EPC significantly decreased the serum activity level of the liver biomarkers ALT and AST in the APAP-treated mice. Furthermore, the hepatic levels of thiobarbituric acid-reactive substances were noticeably lowered, and the levels of total thiol and catalase activity increased significantly with EPC. Histopathological results were strongly consistent with those of the biochemical estimations. The most effective dose was observed at EPC 100 mg/kg, and the therapeutic groups showed better results than the preventive groups. Conclusions: EPC attenuated the liver toxicity in the mice by suppressing oxidative stress and can be considered a preventive and therapeutic agent for inhibiting and resolving the liver damage induced by APAP.

Malignant ureteral obstruction (MUO) is an unpleasant finding resulting from a wide range of malignancies with limited survival prognosis. Its presentation and progression show that it can resist treatment with some stents, including single polymer ureteral stents. With most treatment failures, several treatments are available for the initial management and treatment of benign ureteral obstruction, including therapy with percutaneous nephrostomy (PCN), metallic stents, tandem stents, and other stents. Considering the variety of methods and the heterogeneous population of patients, evaluating the merit of each approach is challenging and needed. Due to the lack of significant studies in this field, these methods leave their performance up to the individual provider. This review aims to provide a framework for urologists to use for individual care and apply it appropriately to patients with MUO. Prospective clinical studies are needed to empower patients with MUO to receive evidence-based treatment and recommendations.

In recent years, the cardiotoxicity and hepatotoxicity induced by chemotherapeutic drugs such as cisplatin (CP) have become significant issues. The current research looks into the effects of sodium hydrosulfide (NaHS) on CP-induced hepatotoxicity and cardiotoxicity in rats. A total of 32 male Sprague Dawley rats were separated into four different groups: (1) control group, received only normal saline; (2) NaHS group, was intraperitoneally injected with NaHS (200 µg/kg/d, dissolved in saline) for 15 days; (3) CP group, was intraperitoneally injected only one dose of CP (5 mg/kg) and (4) CP plus NaHS group, received CP along with NaHS. Blood and tissues samples were harvested for biochemical, histopathological, and immunohistochemical investigations. To determine the data's statistical significance, a one-way analysis of variance was used. CP injection significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), Creatine phospho kinase (CK-MB), cholesterol, low-density lipoprotein (LDL), triglyceride (TG), and lipid peroxidation levels, while high-density lipoprotein (HDL), albumin, glutathione peroxidase, superoxide dismutase, and catalase (CAT) levels were significantly reduced with pathological alterations in liver and heart tissues. Co-treatment NaHS with CP ameliorates the biochemical and histological parameters. Also, Treatment solely with CP resulted in increased tissue expression of interleukin-1β (IL-1β) in liver and heart but co-treatment NaHS with CP reduced the expression of this inflammatory factor. We conclude that NaHS operates in the liver and heart as an anti-inflammatory and powerful free radicals' scavenger to inhibit the toxic effects of CP, both at the biochemical and histopathological levels.

Parkinson's disease (PD) is a complex neurological disorder characterized by a combination of motor and non-motor symptoms (NMS). Antioxidant and anti-inflammatory compounds are considered a potential therapeutic strategy against PD. The present study examined the neuroprotective effects of anethole as a potent antioxidant and anti-inflammatory agent against motor and non-motor deficits induced by rotenone toxicity. Rats were treated with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 5 weeks. After the treatment, behavioral tests were performed to evaluate motor function and depression-/anxiety-like behaviors. After the behavioral tests, rats were decapitated and brains were removed for histological analysis. Striatum samples were also isolated for neurochemical, and molecular analysis. Our data showed that rotenone-induced motor deficit, anxiety-and depression-like behaviors were significantly improved in rats treated with anethole. Furthermore, anethole treatment reduced inflammatory cytokines tumor necrosis factor α (TNFα) and Interleukin 6 (IL-6), and increased anti-inflammatory cytokine IL-4 in the striatum of rotenone-induced PD rats. Western blot analysis showed that treatment with anethole markedly suppressed caspase-3 activation induced by rotenone. Moreover, histological examination of striatum showed an increase in the number of surviving neurons after treatment with anethole. Anethole also significantly enhanced the striatal levels of dopamine in rotenone-induced PD rats. In addition, treatment with L-Dopa as a positive control group had effects similar to those of anethole on histological, neurochemical, and molecular parameters in rotenone-induced parkinsonian rats. Our results suggested the neuroprotective effects of anethole through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms against rotenone-induced toxicity in rats.

This study aimed to develop an oral succinyl chitosan-coated liposomal formulation containing grape seed extract and assess its therapeutic efficacy in rats with bleomycin-induced pulmonary fibrosis. N-succinyl chitosan was synthesized, and the liposomal formulations were prepared and characterized regarding phenolic content assay and morphology. Size, zeta potential, in vitro drug release, and stability. Pulmonary fibrosis was induced by intratracheal bleomycin injection, and hydroxyproline measurements, lung weight, animal body weight, as well as histopathological studies were performed Succinyl chitosan increases the physical stability of the formulation, especially in acidic conditions. Drug release studies revealed that 66.27% of the loaded drug was released from CF2 in an acidic medium in 2 hr, but 92.31% of the drug was released in 8 hr in a pH=7 medium. An in vivo study demonstrated that rats exposed to bleomycin significantly lost weight, while those treated with CF2 (400 mg/kg) partially regained weight. Bleomycin treatment increased the mean lung weight and the amount of hydroxyproline in the lungs; these values were significantly decreased in the group treated with 400 mg/kg CF2 (P <0.05). Histopathological examination confirmed that treatment with 400 mg/kg CF2 improved lung fibrosis. In rats, oral administration of N-succinyl chitosan-coated liposomes containing grape seed extract at the 400 mg/kg dose ameliorates bleomycin-induced pulmonary fibrosis.

Diabetic nephropathy (DN) has been introduced as one of the main microvascular complications in diabetic patients, the most common cause of end-stage renal disease (ESRD). Based on the therapeutic potential of mesenchymal stem cells in tissue repair, we aimed to test the hypothesis that kidney stem cells (KSCs) might be effective in the kidney regeneration process. Stem cells from rat kidney were separated, and the surface stem cell markers were determined by flow cytometry analysis. Thirty-two Sprague Dawley rats were divided into four groups (control, control that received kidney stem cells, diabetic, diabetic treated with stem cells). To establish diabetic, model STZ (streptozotocin) (60 mg/kg) was used. The KSCs were injected into experimental groups via tail vein (2 × 10⁶ cells/rat). In order to determine the impact of stem cells on the function and structure of the kidney, biochemical and histological parameters were measured. Further, the expression of miRNA-29a, miR-192, IL-1β, and TGF-β was determined through the real-time PCR technique. Phosphorylation of Smad2/3 was evaluated by using the standard western blotting. The KSCs significantly reduced blood nitrogen (BUN), serum creatinine (Scr), and 24-h urinary proteins in DN (P < 0.05). IL-1β and TGF-β significantly increased in the kidney of diabetic rats. In addition, the expression of miR-29a is significantly increased, whereas miR-192 decreased after treatment with KSCs (P < 0.05). Diabetic rats showed an increased level of phosphorylation of both Smad2 and Smad3 (P < 0.05). Periodic acid-Schiff (PAS) staining showed improved histopathological changes in the presence of KSCs. Stem cells derived from adult rat kidney may be an option for treating the early DN to improve the functions and structure of kidneys in rats with DN.

Introduction: Different vesicles are created by the cells into extra-cellular space, of which researchers mostly considered exosomes. In fact, the vesicles are secreted by each cell type and are found in the body fluids like urine, blood and breast milk and consist of a certain ingredient of proteins, RNA, lipids and DNA. Objectives: The present study attempted to examine the exosomes derived from tubular cells of the rabbit kidney. Materials and Methods: Exosomes have been derived from rabbit kidney tubular cell line (RK13Cs) supernatant by ultracentrifugation centrifugation treatment techniques. In the next stage, RK13Cs-Exo has been validated by the dimension, morphology and certain bio-markers through the transmission electron microscopy (TEM) and scanning electron microscopy (SEM), Zetasizer nano-analysis, atomic force microscopy (AFM) and western blotting. Results: The morphology of RK13Cs-Exo under TEM and SEM revealed that they have been vesicles shaped like a sphere ~150 nm. Zetasizer nano also indicated that RK13Cs-Exo size has been nearly 50 to 100 nm. Atomic force microscopy image of RK13Cs-Exo showed distinct spherical particles in size range between 50 and 100 nm, corresponding to the TEM. According to the western blotting outputs, exosome markers CD63 and CD9 have been expressed in the RK13Cs-Exo. Conclusion: Tubular cells of the rabbit kidney synthesize large amounts of exosomes under critical environmental conditions, which can extract the produced exosomes. According to the characterization of derived exosomes, they are ideal vehicles for drug delivery.

Aim: Given the increasing usage of cell phones (6.9 billion subscriptions globally) and heterogeneous reports, this study aimed to determine the cell phone effect as non-ionizing radiation on the level of testosterone hormone and sperm parameters in male rats. Material and Methods: Twenty-five matured male Wistar rats were randomly allocated to five groups with the same body weights. Radiofrequency radiation for the exposed groups was 1 h/day call, 2 h/day call, and 50 missed calls/day in 30 days. The other two groups were control (out of any radiation) and positive control (exposed to γ-radiation) groups. Sperm parameters (motility, morphology, viability, counting), histopathology, and serum level of testosterone were measured and analyzed. Results: According to the results, the sperm viability significantly decreased compared to the control group (p<0.001). Also, the findings revealed that the sperm motility in all groups except missed call group (p=0.475). For sperm count and morphology only in Group C (2 h/day call) and Group D (positive control), there were significant reductions compared to the control group (p<0.001). The level of testosterone was not statistically significantly different between the groups (p=0.451). Conclusion: This study suggests that cell phone hazard to infertility was mild to moderate, and cell phone usage might have long-term effects on infertility. However, the cell phone cannot significantly affect the serum testosterone level.