Introduction: Neuronal cell death and glial cell activation are the main pathological findings induced by seizures secondary to oxidative stress. Previous studies have explained neuronal cell death on the basis of cell necrosis and apoptosis. Recent studies have attributed the neuronal loss to autophagy. The proved antioxidant and antifibrotic effect of nilotinib favours its use in the management of epileptic seizures. Aim of the study was to analyse the neuroprotective and antiepileptic effect of nilotinib and explain its mechanism of action. Material and methods: Forty adult male rats were divided into four groups: control, pentylenetetrazol (PTZ) group (injected with PTZ 60 mg/kg, s.c.), pregabalin (Pregb)-PTZ group (pretreated with pregabalin daily 30 mg/kg; orally for 1 week) and nilotinib (NIL)-PTZ group (pretreated with nilotinib, 25 mg/kg daily for 1 week) prior to PTZ. Seizure latency was evaluated, the hippocampus tissue level of antioxidant enzymes was assessed. The histopathological changes in the hippocampus were studied using hematoxylin and eosin stain and immunohistochemical stain for brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), beclin-1, nuclear factor kappa-B (NF-κB) and Bcl-2-like protein 4 (BAX). Results: Nilotinib induced an increase in the latency of seizures, enhanced the antioxidant levels of the γ-aminobutyric acid and nuclear factor (erythroid-derived 2)-like 2 activities together with the improvement of the hippocampal histology. A reduction was reported for BDNF, GFAP, beclin-1, NF-κB and BAX expression in nerve cells. Conclusions: Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy.

Methotrexate (MTX) is a widely used chemotherapeutic agent; nevertheless, the nephrotoxicity associated with its use has limited its clinical use. Rebamipide (REB) is a gastro‐protective agent with diverse promising biological activities. Here, we investigated the renoprotective effects of REB against MTX‐induced nephrotoxicity in rats. Male Wistar rats were allocated into four groups: the normal control group, the REB group (100 mg kg−1 day−1, PO, for 12 days), the MTX group (which received a single injection of 20 mg/kg, ip), and the REB + MTX group (which received 100 mg kg−1 day−1 REB for 7 days before and 5 days after being injected with 20 mg/kg MTX). Interestingly, MTX triggered kidney injury, characterized by renal dysfunction along with histopathological alterations. Moreover, increased reactive oxygen species level and inflammatory response were detected in the kidney of MTX‐treated rats. However, REB prevented MTX‐induced oxidative kidney injury and boosted an antioxidant balance. Mechanistically, REB markedly activated the NRF‐2 protein and upregulated the expression of both SIRT‐1 and FOXO‐3 genes. Additionally, REB administration strongly inhibited the inflammatory response by downregulating both NF‐κB‐p65 and TLR‐4. Finally, the coadministration of REB and MTX activated the mTOR/PI3K/AKT signaling pathway. Simultaneously, REB treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration. Taken together, these results indicate the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.

This study aimed to evaluate the extent of remodelling of intra-decidual segments of the spiral arteries in human deciduas between the 6th and 10th gestational weeks in women with unexplained recurrent miscarriages (RM) in comparison to gestational-matched controls. A possible association with the number, immunoexpressive behaviour and ultrastructural changes of decidual natural killer cells (dNKCs) was investigated. Decidual biopsies were obtained from RM cases (n = 40) and women with no history of spontaneous miscarriage and at least one live birth at term (n = 30). Staining was performed using PAS, anti-CD34 and anti-CD56 antibodies, using an avidin-biotin-peroxides technique. Analysis by means of light and transmission electron microscopy was employed. To determine the extent of remodelling of decidual vessels, a quantitative score was analysed using histological criteria of vascular transformation and then related to the number of CD56(+) dNKCs. In RM, dNKCs were distributed among decidual cells and around the vessels. They possessed numerous polyploidic protrusions on cell membranes crossing from one cell to another. The cells became more irregular and exhibited heterogeneous electron-dense granules in their cytoplasm compared to controls. The non-remodelling score and number of dNKCs were significantly increased in RM group (p < 0.001). The number of dNKCs was significantly correlated with the scores in both control (r = 0.491; p = 0.006) and RM (r = 0.852; p < 0.001) groups. It appears that dNKCs play a key role in impaired decidual artery remodelling that may be involved with early RM. This may be due to increased numbers of cells or impaired cellular interactions resulting from alterations to the ultrastructure.

The present study aimed to evaluate the potential therapeutic effect of pantoprazole, a proton‐pump inhibitor, on precancerous lesion (PCL) in rats. diethylnitrosamine and 2‐acetylaminofluorene were used to induce PCL in rats, in vivo. The rats were treated with three doses of pantoprazole (100, 50, and 25  mg/kg; three times weekly) during the last 4 weeks of the total 10 weeks of the experiment. Blood and liver tissue samples were collected for measurement of the exosomal abundance and exosomal competing endogenous RNA markers. Results revealed that pantoprazole administration had an ameliorating effect on liver function tests and microscopic features of the liver; and decreased exosome abundance in the liver tissue samples and sera of the rats. Meanwhile, the treatment also resulted in a dose‐dependent decrease in exosomal RAB11A mRNA and long noncoding RNA RP11‐513I15.6, which is an important participant in th exosomal secretion process with an increase in exosomal miRNA‐1262. Based on these results, we postulated that pantoprazole has the potential to attenuate liver tumorigenesis in this rat model.

EL-DIN, R. A. S.; EL-SHAHAT, A. E. & ELMANSY, R.A. An electron microscopic study of the antifertility potential of Rosemary (Rosmarinus officinalis L.) in male albino rats. Int. J. Morphol., 30(2):666-672, 2012. SUMMARY:The present work was aimed at studying the antifertility potential of the commonly used herb, rosemary in the male albino rats using electron microscopy as the method of investigation. Ethanolic extract of the rosmary prepared and administered orally in two different doses for a period of three months to the animals. At the end of the experiment animals were sacrificed and testes removed. Sections for the electrone microscopy prepared and changes were observed. The present results showed evident microscopic changes in the testis of the animals received higher dose of the drug. Most of the seminiferous tubules were compressed, having irregular basement membrane and devoid of any spermatogenic cells. The present work revealed a clear morphological evidence of the dose dependent antifertility potential of the rosemary in the male albino rats.

Introduction: Skeletal muscle injuries comprise the greater part of sports-related injuries. Role of growth factors in healing of injured tissue encouraged the use of platelet-rich plasma (PRP). Aim of the work: We aimed to study the effect of PRP on skeletal muscle injury. Materials & Methods: Forty adult male rats were divided into four equal groups; control and 2, 7, 14 days after the injury. The injured muscles were either treated with PRP or left without treatment. The rats were sacrificed and the muscle specimens were processed for histological and immunohistochemical staining for detection of Anti-MyoD, anti-CD34 and anti TGFβ1 followed by morphometric study. Results: PRP treatment induced initial intense inflammatory response with neutrophils and macrophages cell infiltrate subsided in the 7th day. When compared to untreated groups, PRP treated ones showed significant increases in the mean number of regenerating muscle fibers (22.03±4.08) and angiogenesis (10.83±2.46) on the 7th day. The median number of MyoD immunopositive stellate cells showed a significant increase on the 2nd day ,72 (62-78) and then decrease on the 7th day; 28(22-33) to be non significant after 14th days; 4(3-5) of injury. A significant decrease in the mean area % of collagen deposition (2.27±.0.59, 3.68±0.72 and 4.76±0.82) and TGF β1 immunoexpression, medians; 5 (4.20-5.70), 2.50 (2.10-3.50) and 2.30( 1.60-3.20) after 2, 7 and 14 days, respectively, were observed. Conclusions: PRP could exert a promising effect on skeletal muscle injuries via enhancing myogenesis, neovascularization and reduction of fibrosis. Since autologous blood preparations are safe, PRP may serve as a valuable adjunct in management of such injuries.

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In this study, we addressed the potential relationship between prominin-1 (prom1) and vascular endothelial growth factor (VEGFA) in diabetes-induced retinopathy. In total, we examined 28 retinas from 14 rats with streptozotocin-induced diabetes and 30 retinas from 15 untreated control rats. ELISA was used to measure the level of prom1 and VEGFA in retinal tissue homogenates. Immunohistochemical techniques were used with antibodies directed against prom1, VEGFA, and CASP-3. After 180 days of diabetes induction, we performed light and electron microscopy studies on rat eyes to evaluate histopathological changes and to estimate the de novo metric "Diabetic Retinopathy Histopathological Index" (DRHI). These changes were then correlated to the tissue and immunoexpression levels of prom1 and VEGFA. The data showed a significant upregulation of the tissue levels and optical densities (ODs) of VEGFA and prom1 immunoreactivity in diabetic retinas compared with controls. Both the tissue levels and OD values of prom1 and VEGFA correlated significantly with each other and to the diabetic structural changes as calculated by DRHI. Taken together, these data provide new insight into the potential role of prom1 and VEGFA in the development of diabetic retinopathy.