Various studies have indicated that peptic ulcers occurring during the course of diabetic state are more severe and often associated with complications such as gastrointestinal bleeding. This study is an attempt to understand the pathogenesis of indomethacin-induced gastric ulcers occurring during the diabetic state using suitable markers and its amelioration by quercetin and coenzyme Q10 (CoQ10). In this study, diabetic rats showed an increase in the gastric mucosal levels of Molandialdehyde (MDA), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), BAX and p53 and a decrease in the activities of superoxide dismutase (SOD) as compared to normal control (non-diabetic) rats. There was an increase in gastric ulcer index and gastric ulcer lesions in diabetic gastric mucosa when compared to the normal control group. Pre-treatment with quercetin and\or CoQ10 to normal groups or diabetic groups which treated by indomethacin caused a significant decrease in gastric ulcer index, MDA, iNOS, IL-6, TNF-α, BAX and p53 with concomitant increase in SOD activity when compared with normal and diabetic rats treated with indomethacin alone. So quercetin and CoQ10 are effective in protection against indomethacin-induced gastric ulcers in normal and diabetic rats. Our findings could bring new hope for a novel modality of gastric ulcer treatment.

In the current study, we aimed to investigate the mechanistic role of DJ-1/PI3K/Akt survival pathway in ischemia/reperfusion (I/R) induced cerebral damage and to investigate if the Resveratrol (RES) mediates its ischemic neuroprotection through this pathway. RES administration to sham rats, boosted GSH level and SOD activity and downregulated iNOS expression without affecting redox levels of DJ-1 forms nor components of PI3K/Akt pathway including PTEN, p-Akt or p/p-GSK3b. However, RES pre-administration to I/R rats, reduced infarction area, oxidative stress, inflammation and apoptosis. Concomitantly, RES ameliorated the decreased levels of oxidized forms of DJ-1 and enhancing its reduction, increased the nuclear protein expression of Nfr-2 and led to activation of PI3K/Akt survival pathway. In conclusion, overoxidation of DJ-1 is a major factor that contributes to post I/R cerebral damage andits reduction by RES could explain the neuroprotection offered by RSE.

Objective: Atypical antipsychotics represented a major advance in the treatment of schizophrenia and minimizing the extrapyramidal side effects. However, the use of atypical antipsychotics have been linked to weight gain, hyperglycemia, metabolic syndrome and risk of liver affection. Previous studies proposed that vitamin D deficiency may contribute to the development of insulin resistance, metabolic syndrome and more recently fatty liver. The goal of this study wasto investigate the role of vitamin D in protection against the metabolic and hepatic side effects of olanzapine.

Methods: Eighteen female albino rats received treatment by gavage for 5 weeks and divided into; C group: received (0.5ml/day) of normal saline and olive oil (0.2ml) twice weekly, (O) group: received olanzapine (2mg/ kg/day) and olive oil (0.2ml) twice weekly, and (O+D) group: received olanzapine (2mg/kg/day) and vitamin D3 (vit.D3) (125mcg/ Kg) orally by gavage twice weekly. Plasma levels of lipid panel, liver enzymes, glucose, insulin, Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor necrosis-alpha (TNF-α)were determined. H & E staining of liver tissue were performed to assess the effects of vit.D3 treatment on olanzapine-induced histopathology.

Results: Co-administration of vit.D3 caused significant elevation of IL-6, IL-10, HDL/LDL and mild improvement of liver histopathology. However, it caused further elevation of triglycerides (TGs), total cholesterol (TC), very low density lipoproteins (VLDL), TNF-α, liver enzymes, plasma, bilirubin, and impaired glucose tolerance. Insignificant difference in weight gain and abdominal fat was found.

Conclusion: These results suggest that olanzapine-induced disturbed lipid profile and hepatic steatosis is independent of weight gain.Moreover, this study provides an evidence for adverse effects of vitamin D supplementation especially in patients treated with olanzapine.

Recent evidence has suggested that cadmium (Cd) ions-induced neurotoxicity is associated with increased oxidative stress and mitochondrial-dependent and endoplasmic reticulum (ER) stress-induced apoptosis. This study aimed to investigate if rutin hydrate (RH), a well-reported neuroprotective and an antioxidant flavonoid, can ameliorate cadmium chloride (CdCl2)-induced neurotoxicity by inhibiting the resultant ER stress. Rats were divided into 4 groups (n = 16/group) of control, control + RH (100 mg/kg), CdCl₂ (5 mg/kg), and CdCl₂ + RH. All treatments were administered orally for 30 days, on daily basis. Brain homogenates from CdCl₂-treated rats showed increased oxidative stress and induced activation of ER stress characterized by increasing mRNA and protein levels of GRP78, ATF-6, CHOP and Xbp-1 and protein levels of p-elF2α, p-JNK1/2 and cleaved caspase-12. Also, CdCl₂ significantly reduced Bcl-2, enhanced Bax translocation to the mitochondrial membrane, increased cytoplasmic levels of cytochrome-C and caspase-3, and reduced mitochondrial membrane potential (Δψm) (increased Vmax and reduced time to Vmax). In contrast, RH significantly enhanced levels GSH and activities of SOD, GSH-Px, decreased levels of MDA and inhibited mitochondrial permeability transition pore (mtPTP) in the brains of both control and CdCl₂-treated rats. Interestingly, in brain homogenates of CdCl₂-treated rats only, RH reduced all markers of ER stress, increased Bcl-2, reduced mitochondrial Bax translocation and improved mitochondrial coupling. It also reduced cytosolic levels of cytochrome-C, cleaved caspase-3, and cleaved caspase-12. Overall, these findings support the efficiency of RH to inhibit ER stress in brains CdCl2-treated rats which is added to its existing mechanisms of neuroprotection.

Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance (IR). Resveratrol (RES) a potent hypolipidemic dietary polyphenol has been identified for its ability to prevent hepatic steatosis and hepatic IR in high-fat diet (HFD)-fed murine models of NAFLD. In the present study, we have carried an in vivo animal experiment to identify a novel mechanism for RES protective action. Sub-chronic (45 days) RES pretreatment in 3 days HFD-fed adult Wistar rats prevented early hepatic IR through inhibiting PKC/JNK activation; decreasing p-IRS (Ser³⁰⁷) and increasing p-IRS (Tyr⁶¹²), p-Akt (Ser⁴⁷³) and p-GSK3(Ser⁹). These effects of RES were associated with reduced expression of acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT-1) and diacylglycerol:acyl-CoA acyltransferase (DGAT2), two critical enzymes in the glycerol-3-phosphate pathway for de novo triglycerides synthesis. These data indicate that RES protects against NAFLD, initially, by inhibiting the early development of hepatic IR.

This study aimed to analyze the ameliorative effect of Crataegus aronia against type 2 diabetes mellitus (type 2-DM). Type 2-DM rats were treated with the extract and the changes in serum parameters (glucose, insulin, HbA1c and lipids) and hepatic parameters (oxidative stress, inflammation and mRNA levels of GLUT-2 and gluconeogenesis enzymes) were compared to those of control and untreated type 2-DM rats. Also, levels of hepatic insulin receptors 1A (IR-1A) were measured immunohistochemically and compared between groups. In type 2-DM rats, C. aronia significantly improved the oral glucose tolerance test (OGTT), lowered plasma glucose, serum lipid levels and the hepatic glycogen content. Also, it significantly lowered the levels of hepatic lipid peroxidation, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) and enhanced the level of reduced glutathione (GSH) and increased superoxide dismutase (SOD) activity. C. aronia enhanced hepatic mRNA expression of the insulin receptor A isoform (IR-A) and glucose 6-phosphatase (G6Pase), and lowered glucose transporter-2 (GLUT-2) and glycerol kinase (GK) mRNA expression. In conclusion, C. aronia ameliorates T2DM by inhibiting hepatic glucose output.

Resveratrol (RES) has the ability to ameliorate nonalcoholic fatty liver disease (NAFLD) and the mechanism remains unclear. Hence, using high-fat diet (HFD) obese rat model, we investigated the effect of a low dose of RES (20 mg/kg) on the hepatic sterol regulatory element-binding protein (SREBPs) - lipogenesis pathway, enzymes involved in β-oxidation and activity of pancreatic lipase. Four groups of rats (n = 8) of control (12% of calories as fat) and HFD (40% of calories as fat) were administered orally with either normal saline as a vehicle or RES as a concomitant treatment for 8 weeks on a daily basis. Then, various biochemical, histological, and molecular experiments were carried out. RES prevented the development and progression of NAFLD and significantly improved insulin sensitivity through (1) inhibiting the proteolytic cleavage of SREBPs-1 and SREBPs-2 without affecting their precursor mRNA or protein levels, (2) inhibiting free fatty acid β-oxidation and generation of reactive oxygen species through significant inhibition of CPT-1 and UCP-2, and (3) decreasing activity of pancreatic lipase in vivo and in vitro. In conclusion, our findings are the first in the literature to show new mechanisms of the hepatoprotective effect of RES against HFD induced NAFLD in rats.

Background/Aims To assess the safety and efficacy of argon laser photocoagulation as a new modality for the treatment of presumed trematode-induced granulomatous anterior uveitis (PTGAU) in children.