In vitro and in vivo investigation of Argiope bruennichi spider silk-based novel biomaterial for medical use.

As a natural and biocompatible material with high strength and flexibility, spider silk is frequently used in biomedical studies. In this study, the availability of Argiope bruennichi spider silk as a surgical suture material was investigated. The effects of spider silk-based and commercial sutures, with and without Aloe vera coating, on wound healing were evaluated by a rat dorsal skin flap model, postoperatively (7th and 14th days). Biochemical, hematological, histological, immunohistochemical, small angle x-ray scattering (SAXS) analyses and mechanical tests were performed. A. bruennichi silk did not show any cytotoxic effect on the L929 cell line according to MTT and LDH assays, in vitro. The silk materials did not cause any allergic reaction, infection, or systemic effect in rats according to hematological and biochemical analyses. A. bruennichi spider silk group showed a similar healing response to commercial sutures. SAXS analysis showed that the 14th-day applications of A. bruennichi spider silk and A. vera coated commercial suture groups have comparable structural results with control group. In conclusion, A. bruennichi spider silk is biocompatible in line with the parameters examined and shows a healing response similar to the commercial sutures commonly used in the skin.

Investigation of combined effects of propyl paraben and methyl paraben on the hypothalamic-pituitary-adrenal axis in male rats.

The aim of this study was to investigate the endocrine-disrupting effects of methyl paraben (MeP) and propyl paraben (PrP) mixture on the hypothalamic-pituitary-adrenal axis (HPA). In this study, six experimental groups were designated. These groups included three control groups (control, corn oil control, and positive control (50 mg/kg/day BPA)) and three dose groups (10, 100, and 500 mg/kg/day MeP+PrP). MeP with PrP were mixed in a 1:1 ratio and administered to the 42-day-old male rats by oral gavage for 30 days. At the end of the experiment, adrenocorticotropic hormone (ACTH), corticosterone and aldosterone hormones were analyzed in serum. Effects of MeP+PrP on the adrenal glands were investigated by immunohistochemical staining of 11ß hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) enzymes involved in the synthesis steps of corticosterone and aldosterone. Also, pituitary and adrenal glands were examined histopathologically. In the histopathological findings, cortical nodule, congestion, and edema were found in the tissues. In the pituitary gland, cytokeratin rings were detected in all MeP+PrP dose groups, supporting the increase of corticosterone and ACTH. Serum corticosterone, aldosterone, and ACTH hormone levels were increased in the 100 mg/kg/day MeP+PrP and BPA groups. Results obtained from immunohistochemical staining showed that increased staining parallelled increased corticosterone and aldosterone hormone levels. In summary, the results showed that exposure to the MeP+PrP mixture caused a significant increase in ACTH and corticosterone. Also, the MeP+PrP mixture caused a significant increase of CYP11B1 and CYP11B2. MeP+PrP exposure disrupts the normal HPA axis.

Influence of in utero di-n-hexyl phthalate and di-cyclohexyl phthalate exposure on the endocrine glands and T3, T4, and TSH hormone levels of male and female rats: Postnatal outcomes.

The present study was designed to evaluate the effects of di-n-hexyl phthalate (DHP) and di-cyclohexyl phthalate (DCHP) on endocrine organs in rats. Oil control, 20-, 100-, and 500 mg/kg dose groups were selected and administered to pregnant rats on gestational days 6-19 by oral gavage. The neonatal stages of rats continued until postnatal day 20 and the- juvenile stages of rats continued until postnatal day of 32. The rats were allowed to mature until the neonatal and juvenile stages and there after, they were divided into four groups corresponding to the treatment levels. Body and organ weights were recorded, serum was collected, and thyroid, pancreas, pituitary gland, and adrenal gland were removed. There was a decrease in body weights in the 20- and 500mg/kg DHP and in the 20-mg/kg DCHP dose groups in neonatal male rats. In contrast, for female rats, there was an increase in body weights in the 100-mg/kg DCHP dose group and there was a decrease in body weights in the 500-mg/kg DHP dose group. Body weights were increased at 20 and 500 mg/kg in the DHP-exposed juvenile male rats. Serum thyroid-stimulating hormone (TSH) levels were increased in neonatal male rats, while they were increased in the 100-mg/kg DHP group of neonatal and juvenile female rats. Serum triiodothyronine (T3) levels were increased at the high dose of DHP for neonatal male rats and at the low and high dose levels of DCHP for female rats. Serum thyroxine (T4) levels were increased in neonatal rats for DHP. Also, some histopathological changes were observed in the thyroid, pancreas, adrenal, and pituitary gland. In conclusion, it was shown that DHP and DCHP caused negative effects on T3, T4, and TSH hormone levels.

The toxicological effects of bisphenol A and octylphenol on the reproductive system of prepubertal male rats.

The aim of the present study was to assess and compare the individual adverse effects of bisphenol A (BPA) and octylphenol (OP) on the reproductive system of prepubertal male rats. Rats were exposed to BPA and OP at doses of 125 and 250 mg/kg/day, by gavage, for 90 days. At the end of the study, the testes, epididymis, prostate gland, and seminal vesicle were removed and examined histopathologically. Also, 3-ß-hydroxysteroid dehydrogenase expressions were analyzed and serum testosterone and luteinizing hormone (LH) levels were measured. Sperm head count of caput epididymis was performed using a hemocytometer. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. There were significant increases in relative testes weights in BPA125, OP125, and OP250 groups compared with the control. Atrophic tubules, pyknotic tubules, combined tubules, congestion, vacuolization of Sertoli cell, cell debris in the lumen, tubules without sperm, and degeneration of tubules were noted in the tissue specimens obtained from the treatment groups compared with the control group. Sperm head counts were decreased in all treatment groups except for the low-dose BPA group. Testosterone (T) levels decreased in the BPA and high-dose OP treatment groups. LH levels increased in BPA treatment groups and the low-dose OP treatment group and decreased in the high-dose OP group. Epithelial height of high-dose BPA and OP treatment groups increased compared with the control group. Furthermore tubular height of low-dose BPA and high-dose OP groups increased with respect to control levels. In the OP250 treatment group, thyroxine hormone level was increased compared to other groups. Also, in the OP125 treatment group, triiodothyronine hormone level was increased compared with other groups. The results of this study showed that BPA and OP affect the steroidogenic enzyme expression and T production in Leydig cells. In conclusion, BPA and OP have adverse effects on the male reproductive system of prepubertal rats.

Comparative developmental toxicity evaluation of di- n-hexyl phthalate and dicyclohexyl phthalate in rats.

To investigate the effects of di- n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) on the development of fetus and placenta in utero, pregnant rats were exposed to DHP or DCHP at dosages of 0, 20, 100, and 500 mg/kg bw/day, by gavage, on gestational days 6-19. Anogenital distance (AGD) and AGD-body weight1/3 ratio of female fetuses decreased in all treatment groups in a non-dose-response way. The ossification centers of bones and the intensity of Alizarin red stain of the fetuses decreased in all treatment groups. The white blood cell levels of fetuses in DHP and DCHP exposed groups increased at all dosages. Mean cell hemoglobin, hemoglobin concentrations, and hemoglobin levels of all DHP and DCHP treated male and female fetuses were reduced. Histopathologic changes (hemorrhage in labyrinth, degeneration of spongiotrophoblast, hemorrhage, decreased and irregular vessel formation, and edema in the basal zone) were observed in placentas at high dosages of DHP and DCHP. In contrast, there was no change in weight gain of dams in DHP and DCHP exposed groups compared to control, but resorption rate, reduced fetal weight, delayed ossification, placental disruption, and hematologic parameters clearly indicated that in utero DHP and DCHP exposure resulted in intrauterine growth retardation in rats.

Effects of the in-utero dicyclohexyl phthalate and di-n-hexyl phthalate administration on the oxidative stress-induced histopathological changes in the rat liver tissue correlated with serum biochemistry and hematological parameters.

Phthalates are widely used as plasticizers in the industry and are found in cosmetics, food and drink packaging, drugs, toys, households, medical devices, pesticides, personal care products, and paints. Phthalates exert endocrine disrupting and peroxisome proliferator effects in humans and wildlife associated with the pathogenesis of various diseases, including diabetes, obesity, infertility, cardiovascular diseases, metabolic syndrome, and cancer. Since phthalates are metabolized in the liver, which regulates the body's energy metabolism, long or short-term exposure to the phthalates is associated with impaired glucose, lipid, and oxidative stress metabolisms contributing to liver toxicity. However, the impact of in-utero exposure to DHP and DCHP on liver metabolism has not been studied previously. Thus, in this study, we evaluated serum biochemistry parameters, hematological markers, histopathological changes, and oxidative and pentose phosphate pathway (PPP) metabolisms in the liver following in-utero DHP and DCHP administration, respectively, in male and female rats. We found increased relative and absolute liver weights and impaired triglyceride, alanine transaminase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels upon dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP). Histopathological changes, including congestion, sinusoidal dilatation, inflammatory cell infiltration, cells with a pyknotic nucleus, lysis of hepatocytes, and degeneration of hepatic parenchyma have been observed in the liver samples of DHP and DCHP dose groups. Moreover, increased glutathione s-transferase (GST), glucose 6-phosphate dehydrogenase (G6PD), and glutathione reductase (GR) activities have been found in the liver samples of DHP and DCHP-treated rats associated with impaired pentose phosphate pathway (PPP) and oxidative stress metabolism. First time in the literature, we showed that in-utero exposure to DHP and DCHP causes liver damage associated with impaired oxidative stress metabolism in male and female rats. Our data may guide researchers and governments to regulate and restrict phthalates in industrial products.

Endocrine adverse effects of mono(2-ethylhexyl) phthalate and monobutyl phthalate in male pubertal rats.

Considering that research of adverse effects of mono(2-ethylhexyl) phthalate (MEHP) and monobutyl phthalate (MBP), two key metabolites of the most common phthalates used as plasticisers in various daily-life products, has been scattered and limited, the aim of our study was to provide a more comprehensive analysis by focusing on major organ systems, including blood, liver, kidney, and pancreas in 66 male pubertal rats randomised into eleven groups of six. The animals were receiving either metabolite at doses of 25, 50, 100, 200, or 400 mg/kg bw a day by gavage for 28 days. The control group was receiving corn oil. At the end of the experiment, blood samples were collected for biochemical, haematological, and immunological analyses. Samples of kidney, liver, and pancreas were dissected for histopathological analyses. Exposure to either compound resulted in increased liver and decreased pancreas weight, especially at the highest doses. Exposed rats had increased ALT, AST, glucose, and triglyceride levels and decreased total protein and albumin levels. Both compounds increased MCV and decreased haemoglobin levels compared to control. Although they also lowered the insulin level, exposed rats had negative islet cell and insulin antibodies, same as control. Treatment-related histopathological changes included sinusoidal degeneration in the liver, glomerular degeneration in the kidney, and degeneration of pancreatic islets. Our findings document toxic outcomes of MEHP and MBP on endocrine organs in male pubertal rats but also suggest the need for additional studies to better understand the mechanisms behind adverse effects in chronic exposure.

An in vivo assessment of the genotoxic potential of bisphenol A and 4-tert-octylphenol in rats.

Bisphenol A (BPA) and octylphenol (OP) are industrial chemicals used in the manufacture of polycarbonate plastics, epoxy resins, and non-ionic surfactants. In the present study, we investigated the possible in vivo genotoxic effects of these compounds in rats using single-cell gel electrophoresis, the so-called comet assay. Adult male Wistar albino rats were divided randomly into six groups as follows: BPA125 (received 125 mg/kg bw BPA; n = 6), OP125 (received 125 mg/kg bw OP; n = 6), BPA250 (received 250 mg/kg BPA; n = 6), OP250 (received 250 mg/kg bw OP; n = 6), control (n = 5), and MMS (positive control group that received methyl methanesulfonate; n = 3). Both BPA and OP were orally administrated for 4 weeks. Controls were orally inoculated with corn oil for 4 weeks as well. Comet parameters including tail length and tail moment were evaluated for possible genotoxic effects. There were no significant differences in the OP125 and in the BPA125 compared with the control group, regarding tail length and tail moment (P > 0.05). However, there were significant differences in the OP250 and in the BPA250 compared with the control group, regarding tail length and tail moment (P < 0.05 and P < 0.01, respectively). The genotoxic potential of BPA and OP was investigated in vivo; there is a need for further studies exploring further mechanisms of the genotoxic potential of these chemicals in vivo.

Vitamin C coadministration augments bisphenol A, nonylphenol, and octylphenol induced oxidative damage on kidney of rats.

The aim of this study was to investigate whether bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) induce oxidative stress on the kidney tissue of male rats and whether coadministration of vitamin C, an antioxidant, can prevent any possible oxidative stress. The Wistar male rats were divided into seven groups, including control, BPA, NP, OP, BPA+C, NP + C, OP +C. BPA, NP, and OP (25 mg/kg/day) was administered alone; vitamin C (60 mg/kg/day) was administered along with BPA, OP, and NP to the rats for 50 days. There was a decrease in serum concentration of blood urea nitrogen (BUN) in NP and OP groups compared with control group. Vitamin C coadministration with BPA, NP, and OP did not produce significant increase in BUN concentration in BPA +C, NP+ C, and OP + C group as compared with BPA, NP, and OP groups, respectively. The lowest serum creatinine activity and the highest lactate dehydrogenase (LDH) activity was present in kidney of BPA+C, NP+C and OP+C groups compared with BPA, NP, and OP groups. The malondialdehyde (MDA) levels were significantly higher while glutathione (GSH) levels were lower in treatment groups than controls. Furthermore, an increase was observed in MDA levels whereas a decrease was observed in GSH levels in BPA+ C, NP + C, and OP+ C groups compared with BPA, NP, and OP groups, respectively. These finding are in accordance with immunohistochemical staining of MDA and GSH. Histopathological examination of the kidneys of rats in BPA, OP, NP, BPA+ C, NP + C, and OP+ C groups revealed necrotic lesions, congestion, and mononuclear cell infiltration. In conclusion BPA, NP, and OP might induce oxidative damage in kidney of rats. In addition, coadministration of vitamin C with BPA, NP, and OP to male rats augments this damage in the kidney of male rats.

The possible effects of mono butyl phthalate (MBP) and mono (2-ethylhexyl) phthalate (MEHP) on INS-1 pancreatic beta cells.

Mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, is widely used in the production of polyvinyl chloride materials and can be easily accumulated in human body. MBP is the active monoester metabolite of di butyl phthalate that is widely used as plasticizer in many products such as plastic toys, food packaging, personal care products, as well as an additive in lubricants, eliminating foams, and lotions. The presented in-vitro cytotoxicity study focused on time-dependent and combinatory exposure scenarios. We chose these phthalates because they are posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. All experiments performed in INS-1 pancreatic beta cells show moderate cytotoxicity with a time-dependent increase in effectiveness. INS-1 cells were treated with 0.001, 0.01, 0.1, 1, or 10-µM MEHP and MBP for 24, 48, and 72 h. Our results showed that cell viability was decreased and total oxidant levels were increased. Also, mRNA expression levels with asscociated beta cells were measured and for MBP dose groups, all mRNA expression levels were decreased. In conclusion, these findings suggest that, MEHP and MBP are have a negative and distruptor role on pancreatic beta cells and it will be linked with insulin resistance and type 2 diabetes.

Pro-oxidant effect of vitamin C coadministration with bisphenol A, nonylphenol, and octylphenol on the reproductive tract of male rats.

This study was performed to investigate whether bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) induce oxidative stress on the reproductive tract of male rats and if coadministration of vitamin C can prevent any possible oxidative stress. Wistar male rats were divided into seven groups as control (vehicle; olive oil), BPA, NP, OP, BPA+C, NP+C, and OP+C. BPA, OP, and NP groups (25 mg/kg/day) were administered orally to rats three times a week for 45 days. In BPA+C, NP+C, and OP+C groups, vitamin C (60 mg/kg/day) was administered orally along with BPA, OP, and NP (25 mg/kg/day) treatments. Malondialdehyde (MDA) appeared at significantly higher concentrations in BPA-, NP-, and OP-treated groups, when compared to control group. No significant decrease was observed in testes MDA levels of vitamin C coadministrated groups, compared with BPA, NP, and OP treatment groups. Decreased levels of reduced glutathione (GSH) were found in testes of BPA-, NP-, OP-treated rats. No significant increase was observed in testes GSH levels of BPA+C, NP+C, and OP+C groups, compared with BPA, NP, and OP treatment groups. Histological examination showed that vitamin C coadministrated groups had much more congestion areas, atrophy, and germinal cell debris in testes than those observed in other groups. Abnormal sperm percentages of BPA, BPA+C, NP+C, and OP+C groups were increased. In conclusion, the present results demonstrated that BPA, NP, and OP generate reactive oxygen species that cause oxidative damage in testes of rats. Coadministration of vitamin C aggravates this damage.

Histopathologic effects of maternal 4-tert-octylphenol exposure on liver, kidney and spleen of rats at adulthood.

The present study was performed to investigate the potential toxic effects of prenatal exposure to 4-tert-octylphenol (OP) on liver, kidney, spleen, and hematologic parameters of male and female rats in adult life. The rats were treated with OP subcutaneously in utero at doses of control (vehicle, corn oil), 100 or 250 mg/kg per day. After birth, the rats were allowed to grow until adulthood and then liver, kidney and spleen were investigated histopathologically. Also the blood collected from rats were analyzed for any hematologic changes. The red blood cells of male and female rats were decreased in 250 mg/kg per day OP-treated group compared with the control group. micro-RBC of male rats in high dose treatment groups were increased significantly compared with the controls and 100 mg/kg per day treatment groups. micro-RBC of female rats in treatment groups were increased in a dose-dependent manner compared with the controls. In liver, kidney and spleen of male and female rats treated with OP, degeneration of hepatic parenchyma, tubular degeneration and hemorrhage were observed in histopathologic examination. The hemosiderin deposition in spleen of the high-dose group was increased in both male and female rats. In conclusion, findings of this study demonstrate that maternal administration of high doses of OP causes adverse effects on spleen and liver tissues of male and female offsprings at adulthood. Specifically, OP caused decreases in the number of red blood cells indicated by increased destruction in the spleen.

Determination of the healthiness of aquaculture fish by enzymes and histopathological methods.

The health of fishes from select aquacultures was investigated by conducting histopathologic and enzymatic analyses, as well as by examining pollutant accumulation rates in fish tissues ranging in age from juvenile to two years old. Histopathologic examinations demonstrated that the fishes had some abnormalities in their livers, spleens, intestines and reproduction systems, such as lipidation, ovotestis formation, lysis and enlargements of the tissues. The occurrence rate of these abnormalities was not very frequent but also not negligible. Statistical analysis demonstrated that enzyme activity (i.e. CAT, EROD, SOD) and protein concentration fluctuated predominantly by age and season. These parameters were not found to be related to the fish farm or other spatial changes, when their existing environmental conditions were not extreme (i.e. polluted or otherwise unsuitable). Metal concentrations (i.e. Ni, Cu, Zn, As, Cd, Pb and Hg) were never found to be higher than national or international regulatory limits. The quality of the fishes caught from optimal farm conditions may be evaluated as good quality for human consumption.

Effects of butylparaben on antioxidant enzyme activities and histopathological changes in rat tissues.

Butyl p-hydroxybenzoic acid, also known as butylparaben (BP), is one of the most common parabens absorbed by the skin and gastrointestinal tract and metabolised in the liver and kidney. Recent in vivo and in vitro studies have raised concern that BP causes reproductive, development, and teratogenic toxicity. However, BP-induced oxidative stress and its relation to tissue damage has not been widely investigated before. Therefore, we aimed to investigate the effects of butyl 4-hydroxybenzoate on enzyme activities related to the pentose phosphate pathway and on glutathione-dependent enzymes such as glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in kidney, liver, brain, and testis tissues. Male rats were randomly divided into four groups to orally receive corn oil (control) or 200, 400, or 800 mg/kg/day of BP for 14 days. Then we measured G6PD, GR, GST, 6-PGD, and GPx enzyme activities in these tissues and studied histopathological changes. BP treatment caused imbalance in antioxidant enzyme activities and tissue damage in the liver, kidney, brain, and testis. These findings are the first to show the degenerative role of BP on the cellular level. The observed impairment of equivalent homeostasis and antioxidant defence points to oxidative stress as a mechanism behind tissue damage caused by BP.

Data the DEHP induced changes on the trace element and mineral levels in the brain and testis tissues of rats.

Di (2-ethylhexyl) phthalate (DEHP) is used as plasticizer in the industry and belongs to the phthalate family which can induce tissue damage including kidney, liver, and testis as a result of elevated oxidative stress levels. Glutathione reductase (GR), Glucose-6-phosphate dehydrogenase (G6PD), glutathione S-transferase (GST), 6-phosphogluconate dehydrogenase (6PGD), enzyme activities, trace element and mineral levels were evaluated in the brain and testis tissue samples. Our data revealed that, antioxidant enzyme activities in the brain and testis samples were statistically insignificant in the DEHP administered groups compared to the control group except 400 mg/kg/day DEHP dose group in the testis samples. DEHP can disrupt trace element and mineral levels unlike antioxidant enzyme levels that may due to blood-brain and testis-blood barrier and/or short-term exposure to the DEHP. For more detailed information than the data presented in this article, please see the research article "Impact of the Di (2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats" [1].

The effect of vitamin C on bisphenol A, nonylphenol and octylphenol induced brain damages of male rats.

Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) are endocrine-disrupting chemicals that has been shown to exert both toxic and estrogenic effects on mammalian cells. The aim of this study was to investigate if BPA, NP and OP induce oxidative stress on the brain tissue of male rats and if co-administration of vitamin C, an antioxidant, can prevent any possible oxidative stress. The male rats were divided into seven groups as control (vehicle), BPA, NP, OP, BPA+C, NP+C, OP+C. BPA, OP and NP (25 mg/(kg day)) were administrated orally to male Wistar rats for 45 days. In vitamin C co-administration groups (BPA+C, NP+C, OP+C), vitamin C (60 mg/(kg day)) were administrated orally along with BPA, OP and NP (25 mg/(kg day)) treatments. The rats in the control group received olive oil orally. The final body and absolute organ weights of treated rats did not show any significant difference when compared with the control group. Also, there were no significant difference in relative organ weights of BPA, NP, OP, BPA+C and NP+C groups when compared with control group. Only, relative organ weights were increased significantly in OP+C group compared with control group. Decreased levels of reduced glutathione (GSH) were found in the brains of BPA, NP, OP treated rats. The end product of lipid peroxidation, malondialdehyde (MDA), appeared at significantly higher concentrations in the BPA, NP, and OP treated groups when compared to the control group. On the other hand, there were no changes in the brain MDA and GSH levels of BPA+C, NP+C and OP+C groups compared with BPA, NP and OP treatment groups, respectively. In histopathologic examination, the vitamin C co-administrated groups had much more hyperchromatic cells in the brain cortex than that observed in the groups treated with only BPA, NP, and OP. The results of this study demonstrate that BPA, NP and OP generate reactive oxygen species that caused oxidative damage in the brain of male rats. In addition, vitamin C co-administration along with BPA, NP, and OP aggravates this oxidative damage in the brain of rats.

Histopathological effects of 4-tert-octylphenol treatment through the pregnancy period, on the pituitary, adrenal, pancreas, thyroid and parathyroid glands of offspring rats at adulthood.

The present study was carried out to investigate the effects of 4-tert-octylphenol (OP) exposure at fetal period on adrenal, pituitary, thyroid+parathyroid and pancreas tissues of male and female offsprings. Pregnant rats were treated with OP (100 or 250mg/(kgday)) in vehicle (corn oil) or vehicle alone daily from day 1 to 20 of pregnancy. After birth, young rats were allowed to growth until adulthood. While there were no differences in data of organ weight between control and treatment groups, in contrast, a decrease of relative organ weights of thyroid+parathyroid and adrenal in high dose treatment group in male rats, otherwise an increase of final body weights was found in 250mg/(kgday) treatment group in all rats. Also, a lot of histopathological findings were observed in investigated tissues. The results of this study suggest that, the octylphenol which was applied in fetal period causes negative effects on the adrenal, pituitary gland, thyroid+parathyroid and pancreas in rats.

Genotoxic, histologic, immunohistochemical, morphometric and hormonal effects of di-(2-ethylhexyl)-phthalate (DEHP) on reproductive systems in pre-pubertal male rats.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer and people are exposed to various amounts on a daily basis. This study was designed to evaluate the genotoxic, histologic, immunohistochemical, morphometric and hormonal effects of DEHP (100, 200 and 400 mg kg-1 per day DEHP) administered daily to rats by oral gavage for 28 days. The rats were divided into five groups including oil control, positive control (MMS) and treatment groups (100, 200 and 400 mg kg-1 per day DEHP). They were euthanized at the end of the experiment, organ and body weights were recorded and serum was collected for biochemical and hormone analysis. The genotoxic effect was measured in blood and sperm using the Comet assay. The testes, epididymis, prostate gland and seminal vesicle were collected and stained with hematoxylin and eosin for histopathologic analysis. Epithelial height, luminal and tubular diameters (µM) in seminiferous tubules were also measured. Moreover, the study revealed an increase in the DNA damage level in both blood lymphocytes and sperm. At the end of the experiment, the tail intensity showed a significant increase in the 100 mg kg-1 per day (p = 0.032), 200 mg kg-1 per day (p = 0.019) and 400 mg kg-1 per day (p = 0.012) dose groups compared to the control group in blood. Furthermore, testosterone was decreased in all treatment groups compared to the control group. Besides, DEHP caused a significant decrease in the leukocyte levels (p = 0.017) and hemoglobin content, as well as an increased mean cell volume (MCV) count (p = 0.029) in the 400 mg kg-1 per day group when compared to the control values. It is important to indicate that there were apoptotic cells seen in the lumen of testes in the 200 and 400 mg kg-1 per day dose groups using the Tunel method. Therefore, with this study, it has been illustrated that DEHP caused DNA damage in blood and sperm and concrete negative effects on the reproductive system in rats from the pre-pubertal period to the pubertal period. This is a unique study since there has not been any other study that presents the indicated level of DNA damage while considering the genotoxic, histologic, immunohistochemical, morphometric and hormonal effects of DEHP.

Assessing the antiandrogenic properties of propyl paraben using the Hershberger bioassay.

Propyl paraben is a widely used preservative in pharmaceuticals, cosmetics, and foods preventing microbial and fungal contamination. This study was designed to investigate antiandrogenic profiles of propyl paraben following oral doses at 10, 250, and 750 mg kg-1 day to immature male rats using the Hershberger Bioassay. Rats were divided into six groups including solvent control, negative control (0.4 mg kg-1 day testosterone propionate = TP), positive control (3 mg kg-1 day flutamide = FLU) and treatment groups (10, 250, and 750 mg kg-1 day testosterone propionate + Propyl paraben). Propyl paraben (PP) significantly decreased all accessory sex organ weights at each dose of 250 and 750 mg kg-1 day compared to control groups. Thus, we found that propyl paraben had antiandrogenic activity within the supported results of increasing LH levels and histopathologic results such atrophy, hyalinization, and anastomosis on androgenic tissues.

Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.