Sefa Celik

Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats

Diabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45xa0mgxa0kg−1, i.p.) injection into rats. Two days after streptozotocin treatment 10xa0μMxa0kg−1xa0day−1 CAPE was administrated and continued for 60xa0days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-α, 26% for IFN-γ) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-α and IFN-γ in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.

Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers.

The effects of cadmium on performance, antioxidant defense system, liver and kidney functions, and cadmium accumulation in selected tissues of broiler chickens were studied. Whether the possible adverse effects of cadmium would reverse with the antioxidant ascorbic acid was also investigated. Hence, 4 treatment groups (3 replicates of 10 chicks each) were designed in the study: control, ascorbic acid, cadmium, and cadmium plus ascorbic acid. Cadmium was given via the drinking water at a concentration of 25 mg/L for 6 wk. Ascorbic acid was added to the basal diet at 200 mg/kg either alone or with cadmium. Cadmium decreased the body weight (BW), body weight gain (BWG), and feed efficiency (FE) significantly at the end of the experiment, wheras its effect on feed consumption (FC) was not significant. Cadmium increased the plasma malondialdehyde (MDA) level as an indicator of lipid peroxidation and lowered the activity of blood superoxide dismutase (SOD). Liver function enzymes, aspartate amino transferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT) activities were not changed by cadmium. Cadmium ingestion did not alter serum creatinine levels. Although the serum cadmium level was not elevated, cadmium mainly accumulated in the kidneys, liver, pancreas, and muscle. Ascorbic acid supplementation resulted in a reduction of MDA level previously increased by cadmium and a restoration in SOD activity. However, ascorbic acid did not ameliorate the growth inhibitory effect of cadmium nor did it prevent accumulation of cadmium in analyzed tissues. These data indicate that oxidative stress, induced by cadmium, plays a role in decreasing the performance of broilers and that dietary supplementation by ascorbic acid might be useful in reversing the lipid peroxidation induced by cadmium and partly alleviating the adverse effect of cadmium on performance of broilers.

ORIGINAL ARTICLE: Effects of dietary supplementation of synbiotics and phytobiotics on performance, caecal coliform population and some oxidant/antioxidant parameters of broilers

The current study was conducted to evaluate the effects of dietary supplementation of synbiotics and phytobiotics on performance, small intestine weight, pH and caecal coliform counts of broilers. The influences of synbiotics and phytobiotics on oxidant/antioxidant status in the blood of broilers were also assessed. A total of 200 broiler chicks were randomly allotted to four dietary treatments, either fed a basal diet or the same diet supplemented with 1 g/kg synbiotic, 1 g/kg phytobiotic or 1 g/kg synbiotic plus 1 g/kg phytobiotic. The diet supplemented with both synbiotic and phytobiotic had no effect on body weight, body weight gain, feed intake and feed efficiency of broilers at the end of the study (p > 0.05). Neither small intestine weight nor pH was affected by any of the treatments. Supplementation of both synbiotic and phytobiotic to diet decreased the caecal coliform count (p < 0.01). Addition of synbiotics and phytobiotics in combination significantly increased plasma malondialdehyde (MDA) levels (p ≤ 0.05), whereasphytobiotic addition alone showed only a slight increase. Similarly, elevated nitric oxide (NO) level was recorded in the synbiotic- and phytobiotic-fed group and in the phytobiotic-fed group (p ≤ 0.001). Superoxide dismutase (SOD) activities did not differ between the groups. In conclusion, dietary supplementation of synbiotic and phytobiotic improved the gut health by decreasing the caecal total coliform count, but growth performance was not affected by the supplementations. Further investigations are needed to determine the effects of phytobiotics on oxidative/antioxidative metabolism as regards their compositional analysis.

Caffeic acid phenethyl ester suppresses oxidative stress in Escherichia coli-induced pyelonephritis in rats

Although oxidative damage is known to be involved in inflammatory-mediated tissue destruction, modulation of oxygen free radical production represents a new approach to the treatment of inflammatory diseases. Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, has antioxidant, anti-inflammatory and antibacterial properties. For that reason, we aimed to investigate the efficiency of CAPE administration in preventing oxidative damage in pyelonephritis (PYN) caused by Escherichia coli. In this study, 35 Wistar rats were grouped as follows: control, PYN 24xa0h, PYN 48xa0h, PYN 72xa0h, CAPE 24xa0h, CAPE 48xa0h and CAPE 72xa0h. E. coli (1xa0×xa0109 c.f.u.) were inoculated into the rats in both PYN and CAPE groups via urethral catheterization. Ten μM/kg-body weight CAPE was injected to the rats in all CAPE groups 24xa0h before E. coli infection, and injections were repeated at 24-h intervals. Rats were sacrificed 24xa0h, 48xa0h and 72xa0h after infection in both PYN and CAPE groups. Malondialdehyde (MDA) and nitric oxide (NO) levels were significantly increased in kidneys of PYN groups. The activities of the antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XO) were also elevated by E. coli. However, CAPE administration reduced MDA and NO levels, as well as XO activity, although it increased SOD and GSH-Px activities. Histopathological examination showed that CAPE reduced the inflammation grade induced by E. coli. In conclusion, CAPE administrations decrease the oxidative damage occurring in PYN and therefore could be used for medical management of bacterial nephropathy.

Evaluation of oxidative stress and inflammation in long term Brucella melitensis infection

The Brucella genus is able to cause chronic infection in a wide range of mammals including humans. Oxidative events, lipid peroxidation and inflammatory response against Brucella infection have not yet been well elucidated in vivo. We have investigated oxidative/antioxidative status and nitric oxide production in plasma, brain, liver and spleen during a 60 day period of B. melitensis infection in a rat model. In addition, inducible nitric oxide synthase (iNOS), IL-10, IL-12, IFN-gamma and TNF-alpha mRNA transcriptions were analyzed by semiquantitative reverse transcriptase PCR (RT-PCR) in brain samples. Animals were infected with B. melitensis and sacrificed at 7th, 15th, 30th, 45th and 60th day of post-inoculation. Malondialdehyde (MDA), as an indicator of lipid peroxidation, and nitric oxide (NO) concentrations were significantly increased after Brucella inoculation and began to decline to basal levels from 45th day in plasma, liver and spleen. However, iNOS transcription was not induced during the infection period in brains. In contrast, MDA level was increased in brain during the late phase of infection without any change in NO production. The infection did not alter the antioxidant enzyme activities in the tissues; although significantly increased catalase activity was observed between days 30 and 45 in the liver. Transcription analyses demonstrated that IL-10, IL-12 and IFN-gamma mRNA level were not induced in the brain. Only TNF-alpha mRNA was weakly up-regulated in brain 30 days after pathogen inoculation. The results obtained in this study demonstrate that B. melitensis induces lipid peroxidation and NO production in the liver and spleen in the early days of infection, but that these levels subsequently decline. Moreover, Brucella does not appear to induce antioxidant enzyme activities and inflammation during two months of infection. However, the pathogen does stimulate cerebral lipid peroxidation in the late phase of infection without causing significant inflammation.

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.

Preventive effect of rolipram, a phosphodiesterase 4 enzyme inhibitor, on oxidative renal injury in acute ascending pyelonephritis model in rats.

OBJECTIVESnTo evaluate the effects of rolipram, a phosphodiesterase 4 enzyme inhibitor, on Escherichia coli-induced renal oxidative damage in an acute pyelonephritis (PYN) rat model.nnnMETHODSnA total of 35 male Wistar albino rats were randomly divided into 7 groups (n = 5) as follows: control (uninfected), PYN 24 hours, PYN 48 hours, PYN 72 hours, PYN + rolipram 24 hours, PYN + rolipram 48 hours, and PYN + rolipram 72 hours. Ascending PYN was induced in the study groups by E. coli inoculation into the bladder, and the urethras were then occluded by collodium for 4 hours. Rolipram injections (1 mg/kg) were started before bacterial inoculation and repeated at 24-hour intervals in the PYN + rolipram groups until death. The rats were killed at the indicated times. Malondialdehyde and nitric oxide levels and superoxide dismutase and catalase activities were determined in kidney homogenates. Histopathologic examinations were also performed.nnnRESULTSnTissue malondialdehyde and nitric oxide levels and superoxide dismutase and catalase activities were significantly increased in the kidneys from the PYN groups. However, rolipram administration reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. The histopathologic examinations demonstrated that rolipram treatment reduced the inflammation grade in the kidney specimens.nnnCONCLUSIONSnThe results of our study have shown that rolipram has a protective effect on renal tissue from E. coli-induced oxidative injury. Therefore, phosphodiesterase 4 inhibitors might be a novel therapeutic option for the prevention and/or management of acute PYN.

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.