Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells. LCA induced ER stress-related proteins, such as CCAAT-enhancer-binding protein homologous protein (CHOP), and the phosphorylation of eukaryotic initiation factor 2-alpha (p-eIF2α) and c-Jun N-terminal kinases (p-JNK) in both cancer cell-types. The p53 upregulated modulator of apoptosis (PUMA) and B cell lymphoma-like protein 11 (BIM) levels were decreased at overtly toxic LCA concentrations, although PUMA levels increased at lower LCA concentrations in both cell lines. LCA induced autophagy-related conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3BI–LC3BII), and autophagy-related protein ATG5 in PC-3 cells, but not in autophagy-deficient DU-145 cells. LCA (>10 µM) increased levels of reactive oxygen species (ROS) concentration-dependently in PC-3 cells, whereas ROS levels were not affected in DU-145 cells. Salubrinal, an inhibitor of eIF2α dephosphorylation and ER stress, reduced LCA-induced CHOP levels slightly in PC-3, but not DU-145 cells. Salubrinal pre-treatment increased the cytotoxicity of LCA in PC-3 and DU-145 cells and resulted in a statistically significant loss of cell viability at normally non-toxic concentrations of LCA. The late-stage autophagy inhibitor bafilomycin A1 exacerbated LCA toxicity at subtoxic LCA concentrations in PC-3 cells. The antioxidant α-tocotrienol strongly inhibited the toxicity of LCA in PC-3 cells, but not in DU-145 cells. Collectively, although LCA induces autophagy and ER stress in PC-3 cells, these processes appear to be initially of protective nature and subsequently consequential to, but not critical for the ROS-mediated mitochondrial dysfunction and cytotoxicity of LCA. The full mechanism of LCA-induced mitochondrial dysfunction and cytotoxicity in the similarly sensitive DU-145 cells remains to be elucidated.

Background:Royal jelly is a nutritive secretion produced by the worker bees, rich in proteins, carbohydrates, vitamins and minerals.Aim:The present study was designed to determine the possible protective effects of royal jelly against radiation induced oxidative stress, hematological, biochemical and histological alterations in male Wister albino rats.Materials and Methods:Male Wister albino rats were exposed to a fractionated dose of gamma radiation (2 Gy every 3 days up to 8 Gy total doses). Royal jelly was administrated (g/Kg/day) by gavages 14 days before exposure to the 1st radiation fraction and the treatment was continued for 15 days after the 1st irradiation fraction till the end of the experiment. The rats were sacrificed 3rd, equivalent to 3rd post 2nd irradiation fraction, and equivalent to 3rd day post last irradiation fraction.Results:In the present study, gamma- irradiation induced hematological, biochemical and histological effects in male Wister albino rats. In royal jelly treated irradiated group, there was a noticeable decrease recorded in thiobarbituric reactive substances concentration when compared to γ-irradiated group. Also, the serum nitric oxide concentration was significantly improved. The administration of royal jelly to irradiated rats according to the current experimental design significantly ameliorates the changes induced in serum lipid profile. Moreover, in royal jelly treated irradiated group, there was a noticeable amelioration recorded in all hematological parameters along the three experimental intervals. The microscopic examination of cardiac muscle of royal jelly treated irradiated rats demonstrated structural amelioration, improved nuclei and normal features of capillaries and veins in endomysium when compared to gamma-irradiated rats.Conclusion:It was suggested that the biochemical, hematological and histological amelioration observed in royal jelly (g/Kg/day) treated irradiated rats might be due to the antioxidant capacity of royal jelly active constituents.

Older hypertensive patients are at higher risk of developing postoperative atrial fibrillation. Preoperative measurement of atrial electromechanical interval by tissue Doppler echocardiography is a useful predictor of postoperative atrial fibrillation in coronary artery bypass patients.

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Diethylnitrosamine (DEN) is a well-known carcinogen. The aim of our study was to determine the role of olive oil (7 g/kg) with fig (1 g/kg) (OF) and (or) date palm (1 g/kg) (D) fruit extracts during DEN treatment of male Wistar rats. The OF-DEN and (or) D-DEN groups were given oral antioxidants daily for two weeks before and during DEN treatment (21 weeks).The DEN-treated group showed dramatic results for all investigated parameters as compared with the control rats. All OF-DEN and D-DEN groups showed significant improvement in hepatic thiobarbituric acid reactive substances, reduced glutathione, and nitric oxide concentration in the liver tissue, in addition to improvement in serum vascular endothelial growth factor level, alpha-fetoprotein, lipid profile, lipid risk ratios, and the hematological parameters as compared with the DEN-treated group.In conclusion, the administration of OF and (or) D fruit extracts to DEN-treated rats resulted in a considerable improvement in the investigated biochemical and hematological parameters. In addition, the combined OFD treatments showed greater improvements revealing the synergistic effect of the combination.