Abstracts / Toxicology Letters 189S (2009) S57–S273 S123

For the experiment male SHR (strain Okamoto Aoki, n = 12) andNTR, (n = 12), were used. The animals of each strain were dividedinto 2 groups: control group and group treated with alcohol (3 g/kgp.o., 14 days).

Results: GSH level was lower (18%) in the liver of SHRs, comparedto the NTRs, and the ethanol administration decrease it in bothstrains. MDA level was increased in SHR significantly by 16%, com-pared with the NTR, and alcohol treatment enhance this parameteronly in NTRs by 23%. The SOD and catalase enzyme activities weresignificantly reduced in liver of the SHR group, compared with theNTR group, by 39% and by 24% respectively. Alcohol intake increasesignificantly SOD activity by 54% and catalase activity by 56% inSHRs, whereas in the livers of ethanol-treated NTR group, theseenzyme activities were reduced.

Conclusions: The differences in antioxidant status and the effectof ethanol between the strains, might be due to the oxidative stressstate in the hypertensive pathological model

doi:10.1016/j.toxlet.2009.06.423

B23The effect of diazinon on rat brain antioxidant system

Maryam Salehi 1,∗, Mahvash Jafari 2, Masood Saleh Moqadam 1,Mohamad Salimian 2, AliReza Asghari 3, Marzie Nateghi 2,Maryam Abasnejad 4, Mansore Haggholamali 4

1 Razavi Khorasan Payame Noor University, Department ofBiochemistry, Mashhad, Islamic Republic of Iran, 2 Faculty ofMedicine - Military Medicine Institute, Baqiyatallah (a.s) Universityand Razavi Khorasan Payame Noor University, Department ofBiochemistry - Chemical Research Center, Tehran, Islamic Republic ofIran, 3 Faculty of Medicine, Baqiyatallah (a.s) University of MedicalSciences, Department of Physiology and Biophysics, Tehran, IslamicRepublic of Iran, 4 Payame Noor University, Department ofBiochemistry, Tehran, Islamic Republic of Iran

Diazinon (DZN) is a contact organophosphate pesticide and exten-sively used in agriculture. It increases the formation of reactiveoxygen species (ROS) such as superoxide anion, hydrogen perox-ide and hydroxyl radical. In physiological condition a balance exitsbetween production and elimination of free radicals. An imbalancein these processes induces oxidative stress. The aim of this studywas to investigate the effects of DZN on oxidant–antioxidant systemin rat brain tissue. For this purpose, Wistar rats (200–250 g) wererandomly divided into five groups as followed: control and sham(corn oil), and three of groups of DZN receiving different doses (30,50 and 100 mg/kg) by intraperitoneal injection. 24 h after injection,brain tissue of each group was removed and the enzyme activi-ties of superoxide dismutase (SOD) and catalase (CAT) as well asglutathione (GSH) and malondialdehyde (MDA) levels were deter-mined by biochemical methods.

The results show that at concentrations higher than 30 mg/kgDZN, the activities of brain SOD and CAT were significantlyincreased, comparing with the control. GSH level was significantlydecreased. There were no significant changes observed in brainMDA levels.

Our data suggest that an increase in SOD and CAT activities inbrain of rats probably is a function of the increased detoxificationcapacity. Depletion of tissue GSH is a prime factor, which can impairthe cell’s defense against the toxic actions of ROS and may lead toperoxidative cell injury.

doi:10.1016/j.toxlet.2009.06.424

B24Protection by pentoxifylline of malathion-induced toxic stressand mitochondrial damage in rat brain

Akram Ranjbar ∗, Mohammad Abdollahi, Mohammad HosseinGhahremani, Mohammad Sharifzade, Abolfazl Golestani,Mahmmood Ghazi-khansari

Faculty of Pharmacy, Tehran University of Medical Sciences,Toxicology, Tehran, Islamic Republic of Iran

The objective of this study was to investigate the possible protec-tive effects of pentoxifylline as a phosphodiesterase-5 inhibitor onmalathion-induced oxidative damage to rat brain mitochondria.

Rats received malathion (200 mg/kg/day) and pentoxifylline(PTX, 50 mg/kg/day) in combination or alone. Alpha-tocopherol (AT,15 mg/kg/day) was used as a positive standard. After 1 week oftreatment, blood, whole brain tissue, and brain mitochondria wereisolated. The activity of enzymatic scavengers such as glutathioneperoxidase (GPx), catalase (CAT), copper–zinc superoxide dismu-tase (Cu/ZnSOD) and manganese SOD (MnSOD) were measured.The extents of cellular lipid peroxidation (LPO), nitrotyrosine (NOx),and the ratio of reduced versus oxidized glutathione (GSH/GSSG)were determined. The protein expression of MnSOD was deter-mined in brain mitochondria.

Malathion stimulated activities of CAT, Cu/ZnSOD, GPx, andincreased LPO and NOx, and decreased GSH/GSSG in wholebrain homogenate. The changes in CAT, LPO, GPx and GSH/GSSGwere restored by PTX and AT. In plasma samples, malathionincreased CAT, Cu/ZnSOD and GPx activities, increased LPO anddecreased GSH/GSSG, while PTX and AT attenuated malathion-induced changes in GPx, Cu/ZnSOD, LPO and GSH/GSSG. In brainmitochondria, malathion enhanced LPO, NOx, CAT, GPx, MnSOD anddecreased GSH/GSSG as compared to controls, whereas PTX and ATrestored malathion-induced changes in GSH/GSSG, NOx, GPx andCAT. Malathion noticeably enhanced expression of MnSOD proteinas compared to controls. Malathion decreased viability of mito-chondria that was recovered by AT. It is concluded that oxidativedamage is the mechanism of toxicity of malathion in the mitochon-dria that can be recovered by PTX comparable to AT.

doi:10.1016/j.toxlet.2009.06.425

B25Involvement of reactive oxygen and nitrogen species ondoxorubicin-induced toxicity to rat cortical neurons

Miguel Ângelo Lopes 1,2, Andreas Meisel 2, Félix Carvalho 1, Mariade Lourdes Bastos 1,∗

1 Faculty of Pharmacy, University of Porto, Toxicology, Porto, Portugal,2 Charité-Universitätsmedizin, Department of ExperimentalNeurology and Center for Stroke Research, Berlin, Germany

Doxorubicin (DOX) is neurotoxic to serum-free cultures of rat corti-cal neurons in a biphasic concentration manner. For concentrationsup to 0.5 �M, cell death follows an apoptotic pattern, while forhigher concentrations apoptosis is inhibited and necrosis becomesdominant. Considering the potential toxic effects of DOX resultingfrom its redox-cycling, we investigated the generation of reac-tive species and subsequent oxidative stress effects, formation ofquinoproteins, activation of nuclear factor �B (NF-�B), depletion ofenergy levels and consequent cell death in cultures of primary ratcortical cells challenged with this antitumor drug. The influence of