Ahmet Topal

The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity

This study was designed to investigate the qualitative and quantitative changes in brain tissue following aluminum chloride (AlCl3) administration and to determine whether boric acid (BA) has a protective effect against brain damage induced by AlCl 3. For this aim, Sprague-Dawley rats were randomly separated into eight groups: (1) control, (2) AlCl3 (5 mg/kg/day), (3, 4 and 5) BA (3.25, 36 and 58.5 mg/kg/day), (6, 7 and 8) AlCl3 (5 mg/kg/day) plus BA (3.25, 36 and 58.5 mg/kg/day). After the animals were killed, the total numbers of neuron in the brain of all groups were determined using an unbiased stereological analysis. In addition to the stereological analysis, all brains were examined histopathologically by using light and electron microscopy. The stereological and histopathological results indicated a high damage of the rat brain tissues in the AlCl3 and AlCl3 + high dose BA (36 and 58.5) treatment groups. However, protective effects on neuron were observed in the AlCl3 + low dose BA (3.25) group when compared other AlCl3 groups. Our stereological and histopathological findings show that low-dose BA, as a proteasome inhibitor, can decrease the adverse effects of AlCl3 on the cerebral cortex.

Effects of glyphosate on juvenile rainbow trout (Oncorhynchus mykiss): transcriptional and enzymatic analyses of antioxidant defence system, histopathological liver damage and swimming performance.

This study aims to determine the effect of glyphosate on the transcriptional and enzymatic activity of antioxidant metabolism enzymes of juvenile rainbow trout with short term (6, 12, 24, 48 and 96 h) and long term (21 days) exposures followed by a recovery treatment. This study also aims to determine the effects of glyphosate exposure on liver tissue damage and swimming performance due to short term (2.5, 5 and 10 mg/L) and long term (2.5 and 5 mg/L) exposures. Following pesticide administration, ten fish, each as a sample, were caught at 6th, 12th, 24th, 48th and 96th -h for the short term, and at 21st day for the long term exposure study. GPx activity was found to be significantly induced 12 h after the exposure to 2.5 mg/L of glyphosate as compared with the control group. A similar degree of induction was also observed for CAT activity but not for SOD. For long term exposure, except for the GPx activity after exposure to 5 mg/L of glyphosate, the activities of all other enzymes remained on a par with the control group. It was also observed that the levels of gene expression of these enzymes were not comparable with each other. It is assumed that these differences might result from the effect of glyphosate before translation and the possible reasons for this scenario are also discussed. The results of swimming performance are found to be consistent with responses of the antioxidant system, and they are attributed to the energy metabolism. The data are also supported with liver histopathology analysis.

In vivo changes in carbonic anhydrase activity and histopathology of gill and liver tissues after acute exposure to chlorpyrifos in rainbow trout

Abstract Chlorpyrifos is an organophosphate pesticide widely used in agriculture and aquaculture. This study investigated its effects on carbonic anhydrase (CA) enzyme activity and histopathology of rainbow trout gill and liver. The fish were exposed to 2.25 (25 % of 96 h LC50), 4.5 (50 % of 96 h LC50), and 6.75 μg L-1 (75 % of 96 h LC50) of chlorpyrifos for 24, 48, 72, and 96 h. CA activity was measured in liver and gills and histopathological changes were examined by light microscopy. The most common liver changes at most of the chlorpyrifos concentrations were hyperaemia and degenerative changes. Gill tissues were characterised by lamellar hyperaemia, lamellar oedemas, clumping, cellular degeneration, hyperplasia, and lamellar atrophy. CA enzyme activity in the gills decreased at all concentrations at 48, 72, and 96 h after exposure to chlorpyrifos (p<0.05). Similarly, there was a time-dependent decrease in CA activity at all of the concentrations in liver tissues (p<0.05). The present study indicated that chlorpyrifos inhibits CA enzyme activity and causes histopathological damage in gill and liver tissues Sažetak Klorpirifos je organofosforni pesticid široke primjene u poljoprivredi i ribarstvu. U ovome radu istražili smo njegov učinak na aktivnost enzima ugljikove anhidraze te histopatologiju škrga i jetre u kalifornijske pastrve. Ribe su bile izložene klorpirifosu u koncentracijama 2,25 μg L-1 (25 % 96-satnog LC50), 4,5 μg L-1 (50 % 96-satnog LC50) i 6,75 μg L-1 (75 % 96-satnog LC50) tijekom 24, 48, 72 i 96 sati. Aktivnost ugljikove anhidraze mjerena je u jetri i škrgama, a histopatološke promjene promatrane su svjetlosnom mikroskopijom. Najčešće promjene u jetri pri većini koncentracija bile su hiperemija i degenerativne promjene. Na tkivu škrga primijećeni su hiperemija i edemi u škržnim listićima, sljepljivanje i degeneracija stanica, hiperplazija te atrofija škržnih listića. Aktivnost ugljikove anhidraze u škrgama smanjila se pri svim koncentracijama nakon 48, 72 i 96 sati izloženosti (p<0.05). Također je uočeno i smanjenje aktivnosti ugljikove anhidraze u jetri ovisno o duljini izloženosti pri svim koncentracijama (p<0.05). Dobiveni rezultati upućuju na to da klorpirifos inhibira aktivnost ugljikove anhidraze i izaziva značajna histopatološka oštećenja u škrgama i jetri

Does Haloperidol Have Side Effects on Histological and Stereological Structure of the Rat Kidneys

Haloperidol, a typical antipsychotic, is the most commonly prescribed medication for the treatment of mental health problems such as agitation and psychosis. We attempted to determine the effects of haloperidol treatment on the kidneys of female rats. In addition, we aimed to estimate the numerical density, total number, and height of renal glomeruli and the volume and volumetric fractions of the cortex, medulla, and whole kidneys, and tried to determine whether there was a change in these stereological parameters depending on haloperidol treatment. Both the qualitative and quantitative histological features of the kidney samples were analyzed with conventional histopathological and modern stereological methods at the light microscopic level. The total number of glomeruli and numerical density of glomerulus in the haloperidol-treated groups was not changed by increasing the dose in comparison to the control group. The mean height of the glomerulus significantly increased, especially in low-dose groups. In the haloperidol-treated groups, the volumetric fractions of the cortex to the whole kidney of the rats were significantly decreased by increasing the dose. The volumetric fractions of the medulla to the whole kidney of the rats were increased significantly in parallel by the given dose. In addition, we present quantitative findings showing that haloperidol is associated with many alterations in rat kidneys. It was shown that haloperidol may lead to undesirable changes in the kidney after chronic treatment with especially high doses.

Investigation of 8-OHdG, CYP1A, HSP70 and transcriptional analyses of antioxidant defence system in liver tissues of rainbow trout exposed to eprinomectin

&NA; Eprinomectin (EPM), a member of avermectin family, is a semi‐synthetic antibiotic. It has been known that avermectin family enters the aquatic environments and adversely affects the aquatic organisms. Effects of EPM is fully unknown in aquatic organisms especially fish, thus the aim of the present study was to investigate transcriptional changes (sod, cat, gpx) and activities of some antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and malondialdehyde (MDA) levels, oxidative DNA damage (8‐hydroxy‐2‐deoxyguanosine (8‐OHdG)) and transcriptional changes of heat shock protein 70 (HSP70), and cytochromes P4501A (CYP1A) in liver tissues of rainbow trout exposed to sublethal EPM concentration (0.001 &mgr;g/L, 0.002 &mgr;g/L, 0.01 &mgr;g/L, 0.05 &mgr;g/L) for 24 h, 48 h, 72 h and 96 h. The decrease in antioxidant enzyme (SOD, CAT and GPx) activity, transcriptional changes (sod, cat, gpx, HSP70 and CYP1A genes) and increase in MDA level and activity of 8‐OHdG in a dose–time‐dependent manner in the liver of rainbow trout were observed. The down‐regulated of antioxidant (sod, cat and gpx), HSP70 and CYP1A obviously, the severity of which increased with the concentration of EPM and exposure time. The results imply that EPM could induce oxidative damage to the liver tissue of rainbow trout. The information presented in this study is helpful to understand the mechanism of veterinary pharmaceuticals–induced oxidative stress in fishes. HighlightsEPM has biochemical and physiological effects in fish liver.These parameters may be involved in the toxicity mechanism of EPM on rainbow trout.8‐OHdG, CYP1A, HSP70 and antioxidant parameters might be utilized as a potential indicator of exposure to antibiotic in fish.

Evaluation of 8-hydroxy-2-deoxyguanosine and NFkB activation, oxidative stress response, acetylcholinesterase activity, and histopathological changes in rainbow trout brain exposed to linuron

Linuron is a widely used herbicide to control grasses and annual broad leaf weeds. It is known that linuron has toxic effects on different organisms. However, the toxic effects of linuron on aquatic organisms, especially fish, is completely unknown. Thus, we aimed to investigate changes in 8-hydroxy-2-deoxyguanosine (8-OHdG) and nuclear factor kappa B (NFkB) activity, histopathological changes, antioxidant responses and acetylcholinesterase (AChE) activity in rainbow trout brain after exposure to linuron. Fish were exposed to 30μg/L, 120μg/L and 240μg/L concentrations of linuron for twenty-one days. Brain tissues were taken from fish for 8-OHdG and NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity, lipid peroxidation (LPO), and reduced glutathione (GSH) levels. Our data indicated that high linuron concentrations caused a decrease in GSH levels, SOD and CAT activities in brain tissues (p<0.05). LPO levels were significantly increased by 240μg/L linuron. All concentrations caused a significant inhibition in brain AChE enzyme activity (p<0.05). Immunopositivity was detected for 8-OHdG and NFkB, and linuron exposure caused histopathological damage to the brain tissues. The results of this study can provide useful information for understanding of linuron-induced toxicity.

The in vitro and in vivo effects of chlorpyrifos on acetylcholinesterase activity of rainbow trout brain

Chlorpyrifos is widely used to control agricultural pests associated with fruit, nut and vegetable crops, despite its toxic effects and potential brain alterations in aquatic organisms. This study was carried out to determine the in vivo and in vitro effects of chlorpyrifos on rainbow trout brain acetylcholinesterase (AChE) enzyme activity. The fish were exposed to 2.25 µg/L (25% of 96 h LC50), 4.5 µg/L (50% of 96 h LC50) and 6.75 µg/L (75% of 96 h LC50) of chlorpyrifos for 24, 48, 72 and 96 h. In vitro studies, inhibition constants (Ki ) and half-maximal inhibitory concentration (IC50) values for chlorpyrifos were determined by Lineweaver–Burk graphs and by plotting activity percentage vs. [I], respectively. Enzyme activities were determined by a colorimetric method. In fish exposed to chlorpyrifos 2.25 and 4.5 µg/L, enzyme inhibition was not observed (p > 0.05); however, chlorpyrifos exposure to 6.75 µg/L for 72 and 96 h caused a significant decrease in enzyme activity (p < 0.05). The IC50 value of chlorpyrifos was found to be 30 µg/L. These results show that chlorpyrifos may cause direct cellular injury in the brain, and suggest that AChE may be used as a bioindicator for toxicological studies.

The effects of acute boric acid treatment on gill, kidney and muscle tissues in juvenile rainbow trout

Boric acid (BA) is an essential nutrient for plants and many organisms, but it has become an environmental contaminant because of widespread use. Pesticide and its compounds are a serious threat to aquatic organisms. This study was carried out to determine the histopathological effects of acute exposure to BA concentrations in rainbow trout. The fish were exposed to 102 and 103 mg/L concentrations of BA. Tissues were sampled at 6, 12, 24, 48 and 96 h. Histopathological alterations occurring in tissues were common in both doses of BA. Gill tissues showed lamellar oedema, cellulary infiltration, lamellar disorganization, degenerative changes and lamellar thickening. Kidneys had glomerular oedema and glomerulonephritis, degeneration of the tubulary epithelium, interstitial fibrosis and a hyaline cast within the tubular lumens. Muscle tissues displayed interstitial oedema and degenerative and atrophic changes to varying degrees in the myofibrils. Our study shows that BA can be toxic for rainbow trout and cause histopathological damage in fish tissue.

Immunofluorescence/fluorescence assessment of brain-derived neurotrophic factor, c-Fos activation, and apoptosis in the brain of zebrafish (Danio rerio) larvae exposed to glufosinate

&NA; In this study, we investigated the potential neuro‐toxicological mechanism of the glufosinate in the brain of zebrafish larvae in terms of BDNF and c‐Fos proteins by evaluating apoptosis, immunofluorescence BDNF, and c‐FOS activation. We also measured survival rate, hatching rate, and body malformations during 96 h exposure time. For this purpose, zebrafish embryos were treated with graded concentrations of dosing solutions (0.5, 1, 3, and 5 ppm) of glufosinate. End of the treatment, acridine orange staining was used to detect apoptotic cells in the brain of zebrafish larvae at 96 hpf. Texas Red and FITC/GFP labeled protein‐specific antibodies were used in immunofluorescence assay for BDNF and c‐FOS, respectively. The results have indicated that exposure to glufosinate caused to embryonic death, hatching delay, induction of apoptosis, increasing of c‐FOS activity and the level of BDNF in a dose‐dependent manner. As a conclusion, we suggested that c‐Fos might play a role in the regulation of BDNF which responses to prevent the cell from apoptosis even in case of unsuccessful in zebrafish larvae exposed to glufosinate.