Antiapoptotic effects of cerium oxide and yttrium oxide nanoparticles in isolated rat pancreatic islets.

Type I diabetes mellitus is a metabolic disease caused by the impairment of pancreatic ß-cells mainly mediated through oxidative stress and related apoptosis. Islets transplantation seems a promising treatment for these patients, but during islets transplant, various types of stresses related to the isolation and transplantation procedure compromise the function and viability of islets. We recently hypothesized that the combination of cerium oxide (CeO2) and yttrium oxide (Y2O3) nanoparticles with a potential free radical scavenger behavior should be useful to make isolated islets survive until transplanted. In the present study, oxidative stress-induced apoptosis in isolated rat pancreatic islets exposed to hydrogen peroxide (H2O2) and the protective effects of CeO2 and Y2O3 nanoparticles were investigated. Exposure of islets to H2O2 (50 µm, 2 h) increased intracellular oxidant formation such as reactive oxygen species and subsequently apoptosis and decreased viability, glucose-induced adenosine triphosphate (ATP) production and glucose-stimulated insulin secretion. Pretreatment with CeO2 and/or Y2O3 nanoparticles reduced the oxidant formation and apoptosis and increased viability, glucose-induced ATP production and glucose-stimulated insulin secretion. These results suggest that this combination may protect ß-cell apoptosis by improving the oxidative stress-mediated apoptotic pathway.

Examination of Setarud (IMOD™) in the management of patients with severe sepsis.

BACKGROUND AND THE PURPOSE OF THE STUDY: Analysis of current immunomodulating strategies indicates that monovalent approaches are unlikely to restore immunostasis or achieve complete therapy of sepsis. Setarud (IMOD) as a mixture of urtica, carotenoids, urea, and selenium has been recently patented for its potential in reduction of Tumor Necrosis Factor alpha (TNF-α) and Interferon-γ and Interleukin-2 levels. The aim of this study was to examine efficacy of IMOD in the management of patients with severe sepsis. METHODS: Twenty patients with severe sepsis and acute physiology and chronic health evaluation (APACHE) score of more than 20 were randomized to receive standard treatment of severe sepsis (control group) or standard treatment plus IMOD (IMOD group). The group treated with IMOD for 14 days was according to the pilot study and regarding the stability of patient's conditions in the ICU. Of course patients in both groups received standard treatment and all were monitored for 28 days. Blood samples were analyzed for interleukins (IL-1, IL-2, IL-6), plasminogen activator inhibitor (PAI-1), TNF-α, total thiol molecules (TTM), nitric oxide (NO), total antioxidant power (TAP), and lipid peroxidation (LPO). Daily APACHE, Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score (SAPS) were calculated. RESULTS AND MAJOR CONCLUSION: Comparing with controls, IMOD was significantly effective in improving SAPS, SOFA, and APACHE scores, and reduction of mortality rate. Among tested inflammatory biomarkers, IMOD significantly improved TTM and TNF-α values. It is concluded that IMOD might be added as a safe adjutant to standard treatment of severe sepsis.

Study on the oxidative stress status among cement plant workers.

The cement industry is considered as a major pollution problem because of dust and particulate matter emitted at various steps of cement production. In the present study, volunteer male workers from a cement factory were studied for oxidative and nitrosative stress biomarkers in relation to their serum levels of aluminum (Al) and chromium (Cr). The subjects were divided into two groups of direct and indirect exposure. Subject who worked in production steps were considered as direct exposure group, and those who worked in administration building were considered as indirect exposure group. For comparison, healthy subjects at the same age and socioeconomic status were tested as a control group. Serum levels of lipid peroxidation (LP), total antioxidant capacity (TAC), total thiol molecules (TTM), and nitric oxide (NO) as well as Al and Cr were measured. The results indicated a significant increase in Al (P = 0.001) and Cr (P = 0.009) levels in direct-exposed workers in comparison to healthy control group. Further, a significant increase in Al (P = 0.002) and Cr (P = 0.009) levels was observed in direct-exposed workers as compared to indirect-exposed one. Serum levels of TTM and TAC were significantly lower in both direct- and indirect-exposed groups in comparison to healthy control group (P = 0.00). Serum TTM and TAC were significantly lower in direct-exposed workers as compared to indirect-exposed ones (P = 0.00 and P = 0.024, respectively). There was no significant difference on the level of LP and NO among groups. A correlation was found between serum level of Cr, TAC, and platelets between direct- and indirect-exposed groups (P < 0.05). Further correlation was found among serum level of Cr and those of TTM, platelets, and chronic disease (P < 0.05). Chronic disease had a significant influence adjusted to other predictor variables on the post-shift values of Al (P < 0.05). Although plasma levels of Al and Cr were found in normal ranges, analyses confirm their role in impairment of TMM and TAC.

Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics, and DNA damage by an herbal source; evidence for role of free-radical toxic stress.

Cyclophosphamide (CP) as an anticancer alkylating agent has been known as a male reproductive tract toxicant. The aim of this study was to examine whether Satureja khuzestanica essential oil (SKEO) as an established herbal antioxidant, might protect tract rat reproductive system from toxicity of CP. To reach this aim, total antioxidant power (TAP) and lipid peroxidation (LPO) in testis and plasma, blood levels of sex hormones, sperm characteristics, DNA integrity and chromatin quality, and fertility in male rats were tested. Histopathological analysis of testes and epididymides and staining of mast cells were performed for assessment of spermatogenic disorders. CP (6 mg/kg/day) and SKEO (225 mg/kg/day) were administered alone or in combination by gavage for 28 days. In the CP-exposed rats, testicular and plasma LPO increased, TAP decreased, plasma testosterone diminished, and both spermatogenesis and fertility were impaired. In CP-treated rats, a decrease in sperm quality was associated with increased DNA damage and decreased chromatin quality. Coadministration of SKEO significantly improved CP-induced changes in plasma testosterone, sperm quality, spermatogenesis and fertility, toxic stress, and DNA damage. It is concluded that CP-induced toxic effects on androgenesis and spermatogenesis is mediated by free radicals. SKEO protects reproductive system from toxicity of CP through its antioxidant potential and androgenic activity.

Blood beta-glucuronidase as a suitable biomarker at acute exposure of severe organophosphorus poisoning in human.

Organophosphorus compounds are known to cause the selective release of liver microsomal beta-glucuronidase into plasma. Organophophoruses may induce nitrosative stress leading to the generation of nitrogen free radicals and alterations in scavengers of free radicals in many biological systems. In this study, we investigate how acute human organophosphorus intoxication is associated with changes of blood nitric oxide, total thiol molecules, and activities of the acetylcholinesterase and beta-glucuronidase. A total of 21 acute organophosphorus-poisoned patients were recruited into study and were divided into two groups of mildly (13) and severely affected (9); 26 age-matched healthy volunteers were recruited as control group. Results indicated that both mildly and severely affected patients had lower acetylcholinesterase activities as compared to controls. The extent of acetylcholinesterase reduction in the severely affected patients was higher than that of mildly affected patients. A significant increase in serum beta-glucuronidase was observed only in severely affected patients as compared to controls. Both mildly and severely affected patients had lower plasma total thiol molecules as compared to controls. The extent of reduction of total thiol molecules in the severely affected patients was higher than that of mildly affected patients. No significant difference was observed in plasma total nitric oxide of controls and patients. It is concluded that nitrosative stress has a minor role in toxicity of organophosphorus, whereas blood beta-glucuronidase is very sensitive biomarker at high exposure of severe organophosphorus poisoning.

Protection by Ziziphora clinopoides of acetic acid-induced toxic bowel inflammation through reduction of cellular lipid peroxidation and myeloperoxidase activity.

Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested in examining the effect of a total extract from Ziziphora clinopoides, an Iranian folk herbal medicine, in the prevention and control of experimental mouse IBD. Z. clinopoides was administered (75, 150, 300 mg/kg) through drinking water to mice, which dispensed a toxic dose of acetic acid intrarectally. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of the colon were performed. Biochemical evaluation of the inflamed colon was carried out using assays of myeloperoxidase (MPO) activity and thiobarbituric acid reacting substances (TBARS) as indicators of free radical activity and cellular lipid peroxidation. Results indicated that the activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups, while recovered by pretreatment of animals with Z. clinopoides (75-300 mg/kg) and prednisolone. All doses of Z. clinopoides and prednisolone-treated groups showed significant lower score values of macroscopic and microscopic characters when compared to the acetic acid-treated group. The beneficial effect of Z. clinopoides (300 mg/kg) was comparable to that of prednisolone. It is concluded that Z. clinopoides inhibits acetic acid toxic reactions in the mouse bowel through inhibition of cellular oxidative stress. Proper clinical investigation should be carried out to confirm the same activity in human.