Güldeniz Selmanoğlu

Carbendazim induced haematological, biochemical and histopathological changes to the liver and kidney of male rats

Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.

Effects of carbendazim on rat thyroid, parathyroid, pituitary and adrenal glands and their hormones.

The purpose of this study is to determine the effects of low and high dose of carbendazim on the level of certain hormones and endocrine glands (thyroid, parathyroid, adrenal and pituitary glands) of male rats. Carbendazim is a systemic fungicide with activity against a number of plant pathogens. In this study, daily doses of 0, 150, 300 and 600 mg/kg per day carbendazim were applied to male rats by gavage for 15 weeks. At the end of the experiment, T3, T4, TSH, ACTH and GH levels in rat serum were analysed. Thyroid, parathyroid, adrenal and pituitary glands of rats were taken. A significant increase was observed in serum T3 levels of the rats, which were exposed to 300 mg/kg per day carbendazim doses, compared to the serum T3 levels of the control group. There were no differences between the control and carbendazim-treated group of rats regarding serum TSH, T4, ACTH and growth hormone levels. This showed us that carbendazim caused histopathological damages in thyroid, parathyroid and adrenal glands of rats. No changes were observed in pituitary glands of treated rats. These results suggest that a high quantity of subchronic carbendazim exposure affects thyroid, parathyroid and adrenal glands.

Toxicity of food contaminant furan on liver and kidney of growing male rats

Furan is a chemical used in some industrial products and occurs naturally in heat‐treated foods. We aimed to investigate the effects of orally administered furan on liver and kidney in growing Wistar male rats for 90 days. In this respect, biochemical, morphological, histopathological, and histomorphometrical examinations were performed. Three‐ to 4‐week aged rats were divided into five groups of eight animals each; control, oil control; 2, 4, 8 mg/kg/day furan treatment groups. At the end of the experiment, antioxidant enzyme activities and serum AST, ALT, HDL, Urea, etc. levels were analyzed. Malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) were also measured in liver homogenates. Also, liver and kidney were examined morphologically and histopathologically under light microscopy. According to the results of biochemical analysis, ALT, ALP, and LDL levels in treatment groups were significantly different compared with control groups. While LDL levels in treatment groups increased significantly, ALT and ALP levels decreased significantly. No significant changes were observed in liver MDA levels, superoxide dismutase and catalase activities in treatment groups. While IL‐6 levels did not change in treatment groups, furan caused dose‐dependent increases in liver TNF‐α level of rats. In treatment groups, absolute and relative liver weights changed significantly, however, no significant changes were observed in kidney and relative kidney weights. Hyperemic blood vessels in the liver and congestion, edema, fibrosis, and tubular damage in the kidney of rats treated with furan were observed histopathologically. According to histomorphometric examinations, glomeruli diameters and glomerular volume decreased in the kidneys of rats in treatment groups.

Effects of heat-induced food contaminant furan on reproductive system of male rats from weaning through postpuberty.

Furan (C(4)H(4)O) is a volatile, colorless liquid and is used in some segments of the chemical manufacturing industry. It is found in variety of foods such as coffee, jarred and canned foods that undergo heat treatment. This study was designed to investigate the effect of furan exposure on reproductive system of male rats. Three to four weeks old rats were exposed to furan at 2, 4 and 8 mg/kg/day doses by orally for 90 days. Hematology, weights, histology and morphometry of reproductive organs, serum LH and testosterone levels, sperm count and morphology and apoptosis in testis were evaluated. Slight changes were observed in hematological parameters of furan-treated rats. The weights of seminal vesicle reduced significantly whereas the weights of prostate increased significantly in the highest furan dose group. LH and testosterone levels decreased in furan-treated rats. Histological examinations have revealed that furan caused impairments in testis, epididymis and prostate gland. Furan showed no effects on sperm counts and morphology. On the other hand apoptotic cells in testis increased significantly. According to morphometrical examination, the epithelial heights and lumen diameters of the reproductive organs have changed in treatment groups. These results indicate that subchronic furan treatment induces toxicity of the male reproductive system.

Pathological and biochemical effects of therapeutic and supratherapeutic doses of celecoxib in Wistar albino male rats.

Celecoxib is intended for acute pain, menstrual cramps, pain, and inflammation of osteoarthritis and rheumatoid arthritis. The aim of this study was to evaluate the effects of celecoxib (10 and 50 mg/kg/day) treatment on rats orally for 28 days. We examined effects on some biochemical parameters and kidney and liver tissues of celecoxib-treated Wistar albino male rats. At the end of the study, hepatic and renal function tests were performed and liver and kidney of rats were microscopically examined to detect systemic toxicity of celecoxib. Celecoxib-treated rats had statistically significant decreases of cholesterol, total bilirubin, total protein, urea, globulin, blood urea nitrogen, phosphorus, and calcium. Serum gamma glutamyl transferase levels increased in 10- and 50-mg/kg/day celecoxib-treated rats. Histological examinations showed mononuclear cell infiltration, hyperplasia, and cellular degeneration in liver and tubular damage and mononuclear cell infiltration in kidney. We suggest that high doses of celecoxib may cause changes in liver and kidney histopathology, liver function, and in some biochemical parameters.

Evaluation of Patulin Toxicity in the Thymus of Growing Male Rats

Evaluation of Patulin Toxicity in the Thymus of Growing Male Rats Patulin is a mycotoxin produced by several Penicillium, Aspergillus, and Byssachlamys species growing on food products. In this study, we investigated the effects of patulin on the thymus of growing male rats aged five to six weeks. The rats were receiving it orally at a dose of 0.1 mg kg-1 bw a day for either 60 or 90 days. At the end of the experiment, the thymus was examined for histopathology by light microscopy and for epidermal growth factor (EGF) and its receptor (EGFR) by immunolocalisation. For morphometry we used the Bs200prop program to analyse images obtained with the Olympus BX51 light microscope. Cell ultrastructure was studied by electron microscopy. In rats treated with patulin, the thymus showed haemorrhage, plasma cell hyperplasia, a dilation and fibrosis in the cortex, enlarged interstitial tissue between the thymic lobules, enlarged fat tissue, thinning of the cortex, and blurring of the cortico-medullary demarcation. Electron microscopy showed signs of cell destruction, abnormalities of the nucleus and organelles, and loss of mitochondrial cristae. However, no differences were observed in thymus EGF and EGFR immunoreactivity between treated and control rats. Toksični učinci patulina na timus mužjaka štakora u razvoju Patulin je mikotoksin koji proizvode plijesni sojeva Penicillium, Aspergillus i Byssachlamys na različitim prehrambenim proizvodima kao podlozi. Učinke patulina istražili smo na timusu mužjaka štakora u razvoju (dobi 5 do 6 tjedana). Mikotoksin je životinjama davan per os u dnevnoj dozi 0,1 mg kg-1 tj. t. 60 odnosno 90 dana. Na kraju pokusa štakori su žrtvovani, timus je podvrgnut histološkim analizama s pomoću svjetlosne mikroskopije, a imunocitokemijskim je metodama istražena stanična lokalizacija epidermalnog faktora rasta (EGF) i njegova receptora (EGFR). Morfometrijska analiza provedena jes pomoću računalnog programa Bs200prop povezanog u sustav sa svjetlosnim mikroskopom Olympus BX51. Elektronskomikroskopski je istražena ultrastruktura stanica timusa. Utvrđeno je da patulin izaziva krvaranja u timusu, hiperplaziju plazma-stanica, dilataciju i fibrozu u kortikalnoj regiji timusa, širenje intersticijskog tkiva između režnjeva timusa, povećanje masnih stanica, smanjenje debljine kore timusa te nestanak kortiko-medularne demarkacije. Elektronskomikroskopski u tkivu timusa štakora tretiranih patulinom uočeni su znakovi raspadanja stanica, abnormalnosti jezgre i organela te gubitak mitohondrijskih krista. Unatoč navedenomu, na presjecima tkiva kontrolnih štakora i štakora tretiranih patulinom nismo utvrdili razlike u imunoreaktivnosti EGF i EGFR, što bi trebalo dodatno istražiti osjetljivijim molekularnim metodama.

Does furan affect the thymus in growing male rats

Furan has been identified in foods such as heat-treated foods, including coffee, canned meat, hazelnuts, and infant foods and formulas. Children may be exposed to furan via either consumption of these foods or their derivatives. We evaluated the effects of furan on the thymus of weaning male rats in the present study. Five separate groups containing male rats were used: control, oil control, and three furan-treated groups. Furan was given orally to rats in the treatment groups at doses of 2, 4, and 8 mg/kg/day for 90 days. At the end of the experiment, thymus of the rats were examined morphologically, histopathologically, and immunohistochemically. We observed that absolute and relative weights of thymus were decreased significantly in rats treated with 4- and 8-mg/kg/day doses of furan. In histopathological examination, enlargement of interstitial connective tissue between the thymic lobules, lymphocyte depletion, and hemorrhage were observed. We detected an increase in apoptotic cell counts in thymus of the treatment groups. In addition, we found significant differences in the distribution of fibronectin and transforming growth factor-beta in the thymus of the treatment groups. In conclusion, we suggest that furan has affected the thymus in growing male rats.

The effect of Trifolium, Raphanus, and Cistus pollen grains on some blood parameters and mesentery mast cells.

Three kinds of pollen taxa belonging to 3 families (Fabaceae - Trifolium spp., Brassicaceae - Raphanus spp. and Cistaceae - Cistus spp.) and commonly collected by honeybees were fed to mature male rats separately, in the form of 60 mg/animal/day for a 30-day period. The objective of this study was to investigate any positive effects or possible side effects of the use of pollen on the immune system. This was achieved through blood analysis and cell count on blood, hemoglobin, erythrocyte and immune system cells. The cell concentration of mast cells, degranulization and cell localization were investigated in prepared mesentery tissue samples. Histological investigations of the stomach and duedenum sections of pollen-fed rats were carried out to learn the reason for eosinophil gastroenteritis in the alimentary canal. The eosinophil and lymphocyte levels of rats fed with pollen of Trifolium spp., Raphanus spp., and Cistus spp. were observed to have increased blood cell counts, while neutrophil and monocyte levels decreased; different values were found in basophil leucocytes between the pollen groups. Differing reductions in mesentery mast cell concentration, degranulization and cell localization were found. Within the three separate pollens, the rats having been fed with Cistus spp. pollen were observed to have higher blood lymphocyte, eosinophil, hemoglobin and hematocrit values than those fed with the others, as well as low mesentery mast cell concentration. Hemoglobin values were determined to increase at a proportion of between 10.0-11.3%. No difference was found in other blood parameters. The fat proportion of the male rats fed with the three taxa was between 4.03-8.75%, while that for protein proportion was between 16.11-24.25%. Male rats receiving these taxa did not experience allergic reactions and it is possible to argue that the low protein and fat content of these pollens have a strengthening effect on the immune systems by the increase in lymphocyte content and the amount of hemoglobin leads to an increase of oxygen transport capacity in the tissues.

In vivo toxicity of a new antifungal agent 2,4-dithiophenoxy-1-iodo-4-bromo benzene: a follow up on our in vitro study

Abstract Triazole fungicide fluconazole has become the most widely used antifungal agent in the world, mainly because of its ability to penetrate well into body fluids and tissues. However, it has been reported to interact with many drugs and because of its common use, the risk of resistance to fluconazole increases. This calls for new anti-fungal drugs that would be able to replace it. In 2006, a new thialo benzene derivative - 2,4-dithiophenoxy-1-iodo-4-bromo benzene (C18H12S2IBr) - was synthesised with a carbon backbone similar to fluconazole, and, according to the early in vitro tests, much greater efficiency. Followed an in vitro test of its cytotoxicity, in which the new drug showed promising results as an alternative to fluconazole. The aim of this study was take the next step and test C18H12S2IBr toxicity in vivo. We opted for a four-week test on Wistar rats, in which the new antifungal agent was orally applied at doses two and a half and five times lower than those of fluconazole. There were no changes in daily food and water consumption, but weight gain in female rats and relative organ weights changed in the treated groups, pointing to sex-related differences in drug metabolism and effects. Fluconazole significantly increased leukocytes and lowered neutrophils whereas C18H12S2IBr did not, while other haematological changes in respect to the vehicle control were similar between the treated groups. Differences in cytochrome c in the liver and kidney suggested greater apoptotic effect of the new drug, but interpretation remains inconclusive, considering that other key indicators (biochemistry and histopathology) do not support greater toxicity. Considering that C18H12S2IBr is more active at lower concentrations and has comparable toxic effects to fluconazole in rats, this new compound shows some promise in the treatment of fungal infections. Future, more detailed animal studies are needed, that will include drug interactions and molecular toxicity pathways. If the results are promising, clinical studies should follow. Triazolni antifungalni lijek flukonazol danas je najrašireniji antimikotik u svijetu, mahom zato što dobro prodire u tjelesne tekućine i tkiva. Primijećeno je međutim da ulazi u interakciju s drugim lijekovima, a zbog česte uporabe sve je veći i rizik od stvaranja rezistencije na njega. Stoga se traži njegova dostojna zamjena. Godine 2006. sintetiziran je novi derivat tialobenzena - 2,4-ditiofenoksi-1-jodo-4-bromobenzen (C18H12S2IBr). Iako je ugljikova osnovica tog derivata slična onoj flukonazolu, u prvim in vitro istraživanjima pokazao se puno djelotvorniji. Uslijedilo je in vitro istraživanje njegove citotoksičnosti, u kojem se novi spoj pokazao obećavajućom zamjenom za flukonazol. Cilj je ovog istraživanja bio otići korak dalje i istražiti toksičnost C18H12S2IBr in vivo. Odlučili smo se za četverotjedno istraživanje na štakorima Wistar, kojima se je novi antimikotik davao na usta u dozama dva i pol i pet puta nižima od uobičajene doze flukonazola. U životinja nisu primijećene promjene u konzumiranju hrane i vode, ali je relativna težina organa u ženki bila drugačija u odnosu na kontrolnu skupinu, što upućuje na razlike između spolova u metabolizmu lijeka. Za razliku od C18H12S2IBr, flukonazol je prouzročio značajno povišenje razine leukocita i smanjenje neutrofila. Ostale hematološke promjene u odnosu na kontrolnu skupinu bile su slične u skupina koje su primale bilo flukonazol bilo novi lijek. Razlike u imunolokalizaciji citokroma c u jetrima i bubrezima pokazatelj su snažnijeg apoptotičkog učinka novoga lijeka, ali se zbog drugih ključnih pokazatelja (biokemijskih i histopatoloških) ne može ništa zaključiti jer oni ne odgovaraju nalazima citokroma c. S obzirom na to da C18H12S2IBr snažnije djeluje od flukonazola pri nižim koncentracijama, uz podjednake toksične učinke u štakora, ovaj je novi spoj nesumnjivo obećavajuća alternativa liječenju gljivičnih infekcija. Potrebna su daljnja, podrobnija istraživanja u životinja, koja će obuhvatiti interakcije spojeva i molekularne putove toksičnosti. Bude li se lijek i u tim istraživanjima pokazao boljom alternativom, trebalo bi provesti klinička ispitivanja u ljudi.

Vinclozolin exposure throughout pregnancy and its developmental toxicity

It is well known that vinclozolin, commonly used in greenhouse cultivation, causes alterations in the fetal reproductive system. There were no reports about the effects of vinclozolin exposure on the placenta during gestation, therefore, in this study 50 and 100 mg kg−1 body weight per day (bw d−1) doses of vinclozolin were administered by oral gavage to pregnant rats during gestation. They were then subjected to a caesarean section on gestation day 20. Maternal and fetal liver, kidney, heart, thymus, brain, and placenta were examined histopathologically, the placenta and liver tissues were stained immunohistochemically for Vascular Endothelial Growth Factor (VEGF). Morphometric analyses of fetal body lengths, placental measurements, and fetal skeletal staining were performed. The decrease in the placental weight and placental index was significant in the treatment groups. Degenerations in labyrinth region and spongiotrophoblast were detected in the 100 mg kg−1 bw d−1 vinclozolin group. Mononuclear cell infiltration, cellular degeneration and edema in maternal liver samples and an increase in the number of megakaryocytes, cellular degeneration and congestion in fetal liver samples were observed in the treatment groups. VEGF staining was dense in trophoblastic giant cells and spongiotrophoblasts, and less dense in the labyrinth region. VEGF staining increased especially around the central vein in maternal liver. Minor alterations were also observed in the fetal skeleton measurements. These results demonstrated that vinclozolin and/or its metabolites transport to the placenta and induce histopathological changes in the placenta, and maternal and fetal tissues.