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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.

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Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity.Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done.Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin’s therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin’s higher binding affinity than taurine.Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.

Diabetes is a metabolic disorder that share a common underlying feature of hyperglycemia. In addition to hyperglycemia, diabetes is associated with microvascular and macrovascular complications that are the leading causes of morbidity and death in diabetics. Artemisia herba-alba (AHA) is an aromatic plant belongs to the Artemisia genus. The plant known in the traditional medicine for its preventive capacities against several chronic ailments. Forty-five albino adult male rats were randomly divided into 3 groups of 15 animals for each: group 1; control, group 2; STZ induced diabetes, group 3; protective. At the end of the experiment, rats were sacrificed, then we evaluated blood glucose level, serum insulin, α-l-fucosidase (AFU), C-peptide, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total antioxidant capacity (TAC). Liver tissues were evaluated histologically by photomicrographs of liver sections from the three experimental groups using hematoxylin and eosin (H&E). The results of the AHA protective group showed minimal improvement with mild congestion, inflammatory cell infiltrations and some degenerated hepatocytes and the biochemical analysis confirm that. There is a slight improvement in TAC, ALT, AST, C-peptide, and insulin in protective group compared to diabetic group and significant improvement at AFU and α-amylase in protective group compared to diabetic group.

The synthetically new illicit drugs which are called New psychoactive substances (NPS) are the calamity of the modern era. Their danger is much more than the natural drugs of abuse and at the same time, they cannot be detected on regular drug screens making diagnosis very difficult. The number of NPS is growing very fast making their detection more complicated. Another challenge is that their health effects are not well studied and cannot be predicted. Synthetic cannabinoids (SCs) are the most prevalent group in all available NPS. One recent member of the SCs group is AB-CHMINACA. This review article summarizes the available data about AB-CHMINACA. The obtained data were summarized under the following subtitles; historical background, chemical structure, classification, physical characters, pharmacokinetics and pharmacodynamics, toxicity, methods of detection, the magnitude of the problem, and the situation in Egypt. The reviewed studies reveal that AB-CHMINACA like other SC substances are considered toxic with high liability for dependence. Most of the available studies are case reports. The available literature is lacking in specific organ pathology and well-structured toxicity studies.

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