Dilek Guvenc

Therapeutic role of curcumin in oxidative DNA damage caused by formaldehyde

Formaldehyde is a common environmental contaminant that causes oxidative DNA damage in cells by increasing the production of reactive oxygen species. The aim of this study was to investigate the amount of 8‐hydroxy‐deoxyguanosine (8‐OhdG), tumor protein 53(TP53), beta‐amyloid[Aß(1‐42), Aß (1‐40)], total antioxidant capacity (TAC) and malondialdehyde (MDA) and the therapeutic role of curcumin in rat cells with oxidative DNA damage caused by formaldehyde. Method: The control group was given physiological saline for 15 days (ip) and the second group was given 37% formaldehyde (ip) at a dose of 9 mg/kg group every other day. The third group was given 9 mg/kg formaldehyde (ip) every other day and treated therapeutically with 100 mg/kg curcumin every day by gavage. At the end of the trial period, urine, blood, and brain tissue was collected from the rats. Results: The levels of MDA in sera were increased and the TAC, TP53, and Aß (1−40) levels were reduced in the formaldehyde‐treated group with respect to the control group (p<0.005). After treatment with curcumin, the levels of sera MDA were significantly reduced, the TAC, TP53, and Aß (1‐40) levels were significantly increased (P < 0.05). The levels of whole brain Aß (1‐42) and 8‐OhdG were increased in the formaldehyde‐treated group and reduced after treatment with curcumin (P < 0.05). Urinary 8‐OhdG excretion increased in the formaldehyde‐treated group (P < 0.05) and decreased after treatment with curcumin (P > 0.05).

Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats

In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.

Repeated-dose 14-day dermal toxicity of different combinations of some synthetic pyrethroid insecticides, piperonyl butoxide, and tetramethrin in rats

The aim of this study was to evaluate the repeated-dose 14-day dermal toxicity of different combinations of some synthetic pyrethroid insecticides, piperonyl butoxide, and tetramethrin in rats. A total of 70 adult Wistar rats were randomly divided into 7 (6 experimental and 1 control) groups. Different combinations of insecticides were dermally applied to the rats in the experimental groups for 14 days. Clinical observations were performed daily; hematologic and biochemical parameters were also determined. Gross necropsy and histopathologic examinations were performed systematically, and organ weights were recorded. Although the administered doses of the insecticides were relatively lower than their acute dermal toxicity values, a high mortality rate (27 of 60 experimental animals, 45%) was observed. Furthermore, the insecticide combinations caused decreased body weights and feed consumptions, increased organ weights, and hematologic, biochemical, and common histopathologic changes. As a result, the findings showed that although pyrethroids are considered to be of low acute toxicity, they become more toxic when combined with piperonyl butoxide or tetramethrin in certain doses.

Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin

Abstract We investigated dose-related pathological alterations and apoptosis in rat kidney tissue exposed to permethrin. Histopathological findings, apoptotic cell death and urinary 3-phenoxybenzoic acid concentrations (3-PBA) were evaluated. Different doses of permethrin were administered to animals by oro-gastric gavage. A dose-dependent increase of urine 3-PBA concentration was observed in all the permethrin-treated groups. SDS-PAGE separated 30–45 kD and 100–220 kD protein bands in all experimental groups. Histopathologically, degenerative changes were observed in the epithelial lining of the S1, S2, and S3 segments of the renal proximal tubules. Apoptotic cells were seen in the inner stripe of the outer medulla in Group I, and both the cortex and medulla in Groups II and III. Immunohistochemical staining of caspase 3 and caspase 9 also was observed in the same areas. Our results suggest that damage to regions of the proximal tubules is dose-related, and caspase-9-dependent, mitochondria-related apoptotic cell death could play an important role in permethrin-induced nephrotoxicity. We also observed morphologically necrotic cells. We concluded that both necrosis and apoptosis are produced by permethrin.

3-nitrotyrosine levels in dichlorvos-induced neurotoxicity.

Summary The aim of this study was to evaluate dichlorvos toxicity in terms of nitro-oxidative stress by determining 3-nitrotyrosine (3-NT) levels in the fore, mid, and hindbrain regions in acutely exposed rats. Male Sprague- Dawley rats were randomly allocated to three groups of eight. Group 1 was administered a single intraperitoneal dichlorvos dose of 1.8 mg kg-1 (0.1xLD50) and group 2 a dose of 9 mg kg-1 (0.5xLD50). The control group received 0.5 mL saline solution via the same route. 3-NT and tyrosine (TYR) levels were measured using high performance liquid chromatography with a photodiode array detector (HPLC-PDA) and expressed as a ratio of 3-NT to TYR. The 3-NT/1000 TYR ratios increased significantly in the fore-, mid- and hindbrains of the exposed groups compared to control (p<0.01). In the forebrain, the increase was also significant between the treated groups. Our study has confirmed that acute exposure to dichlorvos leads to nitro-oxidative stress in the brain and that 3-NT may play a role in the mechanism of dichlorvos neurotoxicity. Sažetak Cilj je ovog ispitivanja bio ocijeniti neurotoksičnost diklorvosa kroz nitrooksidativni stres mjerenjem razina 3-nitrotirozina (3-NT) u prednjem, središnjem i stražnjem režnju mozga akutno izloženih mužjaka štakora Sprague-Dawley, koji su u tu svrhu nasumce bili podijeljeni u tri skupine po osam životinja. Skupina 1 primila je jednokratnu intraperitonealnu dozu diklorvosa od 1,8 mg kg-1 (0,1xLD50), a skupina 2 dozu od 9 mg kg-1 (0,5xLD50). Kontrolna je skupina primila 0,5 mL fiziološke otopine, također intraperitonealno. Razine 3-NT-a i tirozina (TIR) izmjerene su tekućinskim kromatografom visoke djelotvornosti s detektorom s nizom dioda (HPLC-PDA) te su izražene kao omjer 3-NT:TIR. Omjeri 3-NT/1000 TIR značajno su se povećali u svim režnjevima izloženih skupina (1 i 2) u odnosu na kontrolnu skupinu (p<0,01). Povećanje je također bilo značajno u prednjem režnju skupine 2 u odnosu na skupinu 1, ali nije bilo značajne razlike između izloženih skupina u ostalim režnjevima. Naše je istraživanje potvrdilo da akutna izloženost diklorvosu dovodi do nitrooksidativnog stresa u mozgu te da 3-NT sudjeluje u mehanizmu neurotoksičnosti diklorvosa.

Evaluation of changes in monoamine levels and apoptosis induced by cyfluthrin in rats

The aim of this study was to evaluate monoamine and mitochondrial cytochrome c levels and lipid peroxidation in adult male rats treated with cyfluthrin (14 mg kg−1 dose; approximately 1/10 of the LD50 value) for 14 days. This study also examined cyfluthrin induced apoptosis via the signaling proteins Bcl-2, caspase-9 and caspase-3, and possible anti-apoptotic effects of alpha-basic crystallin (αB-c). Levels of epinephrine (E), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) in the plasma and 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in the striatum to assess neurotransmitter modification. Cyfluthrin administered to the plasma significantly reduced the levels of E and NE and increased 5-HT levels, with no significant increase in lipid peroxidation. In the striatum, cyfluthrin intoxication resulted in a significant increase of the level of 5-HIAA but no significant increase in 5-HT. Apoptosis was detected in astrocytes without a change in the level of cytochrome c but was not detected in neurons. Immunohistochemically caspase-9 positive and Bcl-2 negative neurons were identified. Although these neurons were also negative for both TUNEL staining and caspase-3, they were positive for αB-c. The present study may indicate that cyfluthrin toxicity appears first in neuronal supportive cells, especially astrocytes, rather than in neurons, and that in neurons, αB-c can inhibit the activation of caspase-3 and block apoptosis. In conclusion, our findings support the hypothesis that repeated exposure to cyfluthrin alters neurotransmission of E, NE and 5-HT and induces apoptosis. These data may therefore be important for assessing the safety of cyfluthrin.

Toxic and essential elements in butter from the Black Sea region, Turkey

In this study, 88 randomly selected samples of butter produced in the Black Sea region of Turkey were purchased from different retail markets during different periods and investigated for toxic and essential elements content. Quantitative analyses of elements in the samples were performed using an inductively coupled plasma-mass spectroscopy (ICP-MS). Mean concentrations of As, Cr, Cu, Fe, Mn, Ni, Pb, Se and Zn in the butter samples were 18.93, 100.32, 384.66, 4199.1, 887.47, 168.64, 56.13, 16.34 and 384.66 µg kg−1, respectively. Cd and Co were detected in 19 (mean content 0.29 µg kg−1) and 81 (mean content 3.81 µg kg−1) samples of 88 butter samples, respectively. However, the dietary intake of these elements by the population of the Black Sea region is currently well below the dietary reference intake (DRI) and provisional tolerable weekly intake (PTWI) levels of essential and toxic elements.

Biological Significance of the Overexpression of HSP70 and Alpha B-Crystallin in Rat Substantia Nigra Exposed to Different Doses of Permethrin

The aim of this study was to investigate the possible role of the Heat Shock Protein 70 (HSP70) and Alpha B-crystallin (αBC) in the substantia nigra of rats exposed to permethrin at different doses on the apoptotic cell status. The orogastric gavage method was used to administer the different doses of permethrin (75 mg kg-1 in Group I, 150 mg kg-1 in group II, 300 mg kg-1 in group III) to the rats. Using the Western blot test, all the permethrin-treated groups showed a dose-dependent increase in the expression of HSP70 and αBC when compared to the control group. TUNEL positive apoptotic cells were not detected in the dopaminergic neurons of the substantia nigra after treatment with permethrin; however, upon immunofluorescent staining, intense positive reactions for HSP70 and αBC were observed in all of the treated groups. No immunopositive cells were detected in the tissue sections of the control group. These results suggest that the different administered doses of permethrin did not cause apoptotic cell death in the substantia nigra dopaminergic neurons; however, they did induce an increase in HSP70 and αBC expression. Thus, it appears that HSP70 and αBC could play a neuroprotective role in permethrin-induced neurotoxicity.

Is It Really Necessary to Delay Intranasal Steroid Treatment after FESS? An Animal Study

Objectives The aim of this study is to investigate the effect of early intranasal steroid administration on wound healing after sinus surgery. Study Design Randomized, placebo-controlled, blinded animal study. Setting Animal laboratory. Subjects and Methods Forty-two male New Zealand rabbits underwent bilateral 3-mm punch resection of the concha nasalis ventralis. The animals were divided into 3 groups: saline, late steroid, and early steroid. The saline group received saline drops, the late steroid group received saline drops for 7 days followed by intranasal mometasone furoate 50 µg/nostril/d, and the early steroid group received intranasal mometasone furoate (same dose) starting on postoperative day 1. The animals were sacrificed on postoperative days 10 and 21. Left nasal specimens were examined histopathologically with hematoxylin-eosin and matrix metalloproteinase–9 (MMP-9) stains. Right nasal specimens were examined with high-performance liquid chromatography, and hydroxyproline levels were measured as mg/g in wet tissue. Results Late steroid and early steroid groups were similar with regard to MMP-9 staining on days 10 and 21. On day 10, the early steroid group revealed significantly intense MMP-9 staining when compared with the saline group, and the late steroid and early steroid groups revealed significant fibrosis when compared with the saline group. Hydroxyproline levels were similar in all groups on day 10. The early steroid group revealed significantly higher hydroxyproline levels when compared with the late steroid group on day 21. Conclusion Our findings showed that early intranasal steroid administration after sinus surgery in an animal model has no detrimental effects with regard to wound-healing parameters.

Comparison of lidocaine metabolism for different anesthesia techniques in rabbits with liver disease

OBJECTIVE This study was designed to investigate the serum lidocaine concentrations (SLC) after local infiltration anesthesia (IA) and mandibular anesthesias (MA) in rabbits with carbon tetrachloride (CCl₄)-induced chronic liver damage (CLD). STUDY DESIGN Fourteen rabbits were administered CCl₄ in group 1, MA (CLD-MA; n = 7); in group 2, IA (CLD-IA; n = 7); in group 3, MA (H-MA; n = 7); and in group 4, IA (H-IA; n = 6) was performed. SLC were measured. RESULTS SLC showed difference over time. At the 10th minute, mean SLC in IA groups were higher than in MA groups. At the 120th minute, the highest mean concentration was found in the CLD-IA group. CONCLUSIONS SLC increases in CLD, and serum lidocaine concentration after IA in the mandibular anterior region is higher than it is after MA.