Altug Kucukgul

Effect of Lycopene Administration on Plasma Glucose, Oxidative Stress and Body Weight in Streptozotocin Diabetic Rats

Abstract Duzguner, V., Kucukgul, A., Erdogan, S., Celik, S. and Sahin, K. 2008. Effect of lycopene administration on plasma glucose, oxidative stress and body weight in streptozotocin diabetic rats. J. Appl. Anim. Res., 33: 17–20. To evaluate the role of lycopene, a carotenoid antioxidant, on streptozotocin (STZ)-induced diabetic rats, 12 female rats received a single intraperitonial injection of STZ at a dose of 45 mg/kg body weight of which 6 were given 10 mg/kg lycopene orally (test group) once daily for 21 days. The administration of STZ caused a significant increase in plasma glucose and decrease in body weight. The supplementation of lycopene significantly reduced diabetic plasma glucose level by 25% and prevented body weight loss starting from 14th day of lycopene administration. Although tissue lipid peroxidation and nitric oxide (NO) levels were unchanged, lycopene administration significantly reduced diabetes-elevated lipid peroxidation and NO in plasma. It was concluded that lycopene supplementation may be valuable for correcting hyperglycemia and preventing diabetic complications caused by lipid peroxidation and free radicals.

Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production

Brucella species are able to survive and replicate within the phagocytic cells and cause chronic infections in domestic animals and humans. Modulation of programmed cell death by Brucella spp. may be one of the reasons of the chronicity of the infection. In this study, whether cisplatin treatment, an apoptotic anticancer agent, would enhance the host resistance against Brucella melitensis-infected human macrophage-like cells was investigated. The infection neither induced inflammation nor oxidative stress. But, Brucella caused a decrease in infected macrophage viability of 36% at 48 h postinfection (p.i.) as compared with uninfected cells. Treatment of infected macrophages with 20 microM cisplatin for 48 h caused a large increase in nitric oxide (NO) levels in a time-dependent manner via induction of iNOS transcription. Cisplatin also enhanced glutathione peroxidase, myeloperoxidase and xanthine oxidase activities, providing evidence of generation of reactive free radicals. N-acetylcysteine was able to decrease cisplatin-induced NO, and prevented the agent-induced apoptosis, similar to effects found in l-NAME (N(G)-nitro-l-arginine methyl ester) treatment. Cisplatin stimulated inflammation through the induction of TNF-alpha and IL-12 secretion, and down-regulated Brucella-stimulated IL-10 transcription. The number of infected cells and their viability were decreased by 80% at 48 h p.i. by cisplatin in comparison with infected cells. Similar to this result, cisplatin treatment resulted in reduced intracellular CFU of B. melitensis being reduced by 80% at 48 h p.i. These findings demonstrate that pharmacological agents such as cisplatin may be considered to influence immune responses and apoptosis to help decrease Brucella-infected cell number.

Low concentration of oleic acid exacerbates LPS-induced cell death and inflammation in human alveolar epithelial cells.

ABSTRACT Purpose: The current study aimed to investigate in vitro effects of oleic acid on lipopolysaccharide (LPS)-induced acute lung injury in the human lung epithelial cells (A549). Materials and Methods: The cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests. Selected gene expression levels were analyzed by Real-Time Quantitative-Polymerase Chain Reaction (RT-qPCR). Results: 24 hours of LPS (100 ng/mL) exposure decreased the cells’ viability by 44.6% compared to untreated control. Low concentration (2.5 nM) of oleic acid slightly suppressed the cell survival by 9.1% analyzed 24 hours after incubation. However, oleic acid pretreatment before LPS exposure significantly increased cell survival loss to 63.9%. LPS exposure decreased the expressions of catalase (CAT) and glutathione peroxidase (GPx) mRNA levels by 2.8 and 2.5 fold, respectively. Moreover, pretreatment of the cells with oleic acid strengthened LPS-decreased expressions of CAT and GPx genes by 3.5 and 6.7 fold, respectively. The mRNA expressions of superoxide dismutase (SOD), induced nitric oxide synthase (iNOS), interleukin-1β, IL-12, COX-2, caspase-3 and caspase-8 were increased by 2.4, 2.2, 2.2, 2.3, 3.0, 2.6, and 2.5 fold, respectively, by LPS, and oleic acid pretreatment significantly potentiated the effect of LPS. Conclusion: Oleic acid worsens LPS-induced cell death by potentiating oxidative stress and inflammation in A549 lung epithelial cells.

Silencing of PrPC (prion protein) expression does not affect Brucella melitensis infection in human derived microglia cells

Cellular prion proteins (PrP(C)) are mainly expressed in the central nervous system where they have antioxidant effects and a role in the endocytosis of bacteria within cells. These proteins also have some crucial biological functions including roles in neurotransmission, signal transduction and programmed cell death. However, the role of prion proteins in neuronal Brucella infection, specifically in the interaction of the pathogen and the host cell is controversial. In the present study, the silencing of PrP(C) mRNA by small interfering RNA (siRNA) transfection was investigated in human microglia cells infected with Brucella melitensis. More than 70% of prion proteins were down-regulated in microglia by siRNA transfection and this caused a slight decrease in the cellular viability of the control cells. Silencing of PrP(C) suppressed the antioxidant systems, though it led to an up-regulation of pro-inflammatory cytokines such as IL-12 and TNF-α as demonstrated by qRT-PCR analysis. B. melitensis infection of prion protein-silenced cells led to increase host viability, but had no effect on bacterial phagocytosis. According to the present study, there is no significant effect of prion proteins on phagocytosis and intracellular killing of B. melitensis in microglia cells.