Background: Infertility is a major health problem affecting human life. Multiple factors contribute to male infertility. The most important one is exposure to environmental contaminants (e.g. Bisphenol A (BPA)). Aim of the work: To study the possible protective effect of Omega 3 against BPA induced changes in the pituitary testicular axis in rats. Material and method: 30 adult male albino rats were used in the study. They were divided equally into 3 groups 10 animals each. Group I served as control. Group II received BPA in a dose 1.2 mg/kg orally 6 days a week. Group III received Omega 3 in a dose 0.4 g/kg subcutaneously in addition to BPA of the same previous dose and duration. At the time of sacrifice, all rats were anesthetized with ether.Blood samples were collected for estimation of testosterone, LH, FSH and prolactin. The testes and pituitary were dissected out and processed for histological and immunohistochemical study for Caspase 3, PCNA and prolactin. The number of Caspase 3 and PCNA positive cells were counted and statistically analyzed. Results: Marked decrease in serum LH, testosterone with marked increase in serum prolactin was observed in BPA treated group. Spermatogenic cells were disorganized and degenerated. Spermatids had fragmented pyknotic nuclei. A significant increase in the rate of apoptosis and a significant decrease in the rate of proliferation of germ cells were detected on BPA exposure compared to the control. Examination of pars distalis revealed degenerative changes in acidophils and basophils in group II animals with decreased intensity of reactive mammotrophs. These changes were ameliorated in group III by administration of Omega 3 fatty acids. Conclusion: Omega 3 may protect against BPA hazardous effects through pituitary testicular axis pathway.

In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6-and 12-hour intervals. Parietal cells (H + , K +-ATPase β-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our | 231 GEBRIL Et aL. How to cite this article: Gebril SM, Ito Y, Shibata M-A, et al. Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis-and autophagy-associated molecules.

Doxorubicin (DOX) is an anthracycline antibiotic and a quinone-containing chemotherapeutic drug used for various types of cancers. However, as with most anticancer drugs, it causes many toxic effects, one of them is cognitive impairment. The present study investigated the prophylactic and ameliorative effect of n-acetylcysteine (NAC) against DOX-induced neurotoxicity in rats. Rats were divided into four groups. Control group: rats received saline. NAC treated group: rats received NAC (100 mg/kg, p.o.) daily for 35 days. DOX-treated group: rats received DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. DOX+NAC treated group 1: rats received NAC (100 mg/kg, p.o.) daily for 35 days and DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28). DOX+NAC treated group 2: rats received NAC (100 mg/kg, p.o.) daily started at the 7th day of the experiment till the end of the experiment and DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. The present results showed a significant reduction in the body weight, which was associated with a significant increase in brain to body weight ratio in DOX-treated rats. Tumor necrosis factor (TNF-α) level, malondialdehyde (MDA) and total protein levels were significantly elevated. Whilst, reduced glutathione (GSH) and glutathione peroxidase (GPx) levels were significantly decreased. Moreover, there were histopathological abnormalities in the brain tissue of DOX-treated rats, as most of the neurons degenerated and the blood vessels surrounded with wide perivascular spaces. In addition, the neuropil was vacuolated. The present study demonstrated that NAC has a neuroprotective effect on the brain damage induced by DOX, through inhibition of inflammation and oxidative stress. This neuroprotective effect was more pronounced in DOX+NAC treated group 1, as it produced a significant increase in brain GSH and GPx levels and more improvement in the histopathological abnormality compared to DOX+NAC treated group 2.

Background: Radiation induced brain and cerebellum injury is common in patients receiving radiotherapy for head and neck tumors. Administration of antioxidants before radiation as vitamin E, nigella sativa oil and melatonin could be valuable in limiting this injury. Material and Methods: 40 rats were divided into five different groups. Group Ι: served as the control group and subdivided into 4subgroups. subroup Ia: negative control, subgroup Ib: animals received vitamin E only (300 mg/kg orally once, subgroup Ic: animals received nigella sativa oil only (1ml/kg orally once and subgroup Id: animals received melatonin only 100 mg/ kg intraperitoneally once: Group ΙΙ: animals were exposed to x ray irradiation (XRI) (8 Gy whole body). Group ΙΙΙ: animals were pretreated with vitamin E (300 mg/kg orally once 1h before XRI. Group ΙV: animals were pretreated with nigella sativa oil(1ml/kg orally once1h before XRI). Group V: animals were pretreated with melatonin (100 mg/kg intraperitoneally once 1h before XRI). Animals were sacrificed 48h after irradiation. Brain and cerebellum were dissected, formalin fixed and processed for histological and glial fibrillary acidic protein (GFAP) immunostainig. The number of GFAP positive astrocytes were counted and statistically analyzed using SPSS program. Results: Radiation induced loss of lamellar pattern in the cerebral cortex with degeneration and necrosis of cortical nerve cells. In the cerebellum, purkinje cell degeneration was observed. Radiation induced a significant increase in the number of GFAP positive astrocytes in both cerebral and cererbellar cortices compared to the control group. In groups treated with vitamin E, nigella sativa oil and melatonin, there was partial improvement in cerebral and cerebellar changes with a significant decrease in the number of GFAP positive astrocytes. Conclusion: The use of antioxidants such as vitamin E, nigella and melatonin could limit radiation induced injury in brain and cerebellum.

Introduction: Cyclosporine A (CsA) is considered powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and also used in autoimmune diseases. However, its use is limited by many side effects mainly nephrotoxicity. NAC is an antioxidant found to reduce CsA toxicity. Aim of the work: The study aims to determine the effect of exposure to cyclosporine on the kidney and to investigate the protective role of NAC. Methods: the study conducted on 50 adult male albino rats for 4 weeks, divided into 5 groups, group A the negative control group, group B the olive oil group (0.5 ml/d orally), group C the cyclosporine group (25mg/kg/d orally), group D the NAC group (600mg/kg/d orally) and group E the cyclosporine+NAC group. At the end of the study the evaluation was done by biochemical analysis and histopathology. Results: cyclosporine significantly affects the kidney by morphological changes in the form of dilatation of urinary space with congestion and lobulation of glomerullar capillaries in the renal corpusle. Proximal convoluted tubules showed degeneration of their cells with irregularity and destruction of brush border. Degeneration of distal convoluted tubules with exfoliation of some cells inside the lumen and the peritubular capillaries were congested and extravasated. Also cyclosporine affects the kidney by increasing serum urea and creatinine levels, while coadministration of NAC with cyclosporine attenuate its effects. Conclusion: cyclosporine causes renal injury through oxidative stress and NAC as an antioxidant attenuates but not fully protect against cyclosporine induced injuries.