The effect of aqueous extract of Rosa damascena on formaldehyde-induced toxicity in mice testes

Context: Rosa damascena L. (Rosaceae) (RD) essential oil and extracts are commonly used as a flavour in herbal medicine which increase libido. Previous studies have shown inhalation of RD flower’s oil increases libido and causes protective effects in formaldehyde (FA)-induced testicular damage.

Objective: The protective effects of aqueous extract of RD on the male reproductive system of mice were examined following FA-induced damage.

Materials and methods: Forty-eight adult NMRI male mice were randomly assigned to six groups (n?=?8): control (normal saline, 10?mg/kg); RD40 (40?mg/kg, p.o.); FA treated (10?mg/kg of 10%, i.p.) and FA?+?RD treated at 10, 20 and 40?mg/kg (FA?+?RD10), (FA?+?RD20) and (FA?+?RD40), respectively, for 40 days. At the end of treatment regimes, serum testosterone (T) level and the reproductive activity, viz. body/organ weights, testicular structure and sperm characteristics were studied.

Results: Formaldehyde administration significantly decreased serum T level (p?p?p?Discussion and conclusions: We may conclude that RD flower extract can withstand effects of FA in the male reproductive system of mice possibly due to its antioxidative properties.     

Quercetin and vitamin E attenuate Bonny Light crude oil-induced alterations in testicular apoptosis,stress proteins and steroidogenic acute regulatory protein in Wistar rats

Studies have shown the reproductive effects of Bonny Light crude oil (BLCO) via the mechanism of oxidative stress and testicular apoptosis. We investigated the protective role of quercetin and vitamin E on BLCO-induced testicular apoptosis. Experimental rats were divided into four groups of four each. Animals were orally administered 2?ml/kg corn oil (control: group 1), BLCO-800?mg/kg body weight?+?10?mg/kg quercetin (group 2), BLCO-800?mg/kg body weight?+?50?mg/kg vitamin E (group 3) and BLCO-800?mg/kg body weight only (group 4) for 7 d. Protein levels of caspase 3, FasL, NF-kB, steroidogenic acute regulatory protein and stress response proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunofluorescence staining was used to quantify the expression of caspase 3, FasL and NF-kB. Apoptosis was quantified by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptosis-related proteins by 50% and above after 7 d following BLCO exposure and a concomitant increase in expression of caspase 3, FasL and NF-kB expression by immunofluorescence staining. Apoptosis showed a significant increase in TUNEL positive cells. Co-administration with quercetin or vitamin E reversed BLCO-induced apoptosis and levels of stress protein, relative to control. These findings suggest that quercetin and vitamin E may confer protection against BLCO-induced testicular oxidative stress-related apoptosis.     

Reproductive Effects of 4-Vinylcyclohexene in Swiss Mice Assessed by a Continuous Breeding Protocol

4-Vinylcyclohexene (VCH), a dimer of 1,3-butadiene, was evaluatedfor reproductive toxicity in Swiss (CD-l) mice using the continuousbreeding protocol (NTP, 1989). VCH in corn oil was administeredby gavage at doses of 0, 100, 250, and 500 mg/kg/day to animalsthat were housed in same sex pairs for 1 week and then cohabitedin breeding pairs for 14 weeks. During cohabitation, newbornlitters were euthanized immediately after evaluation on postnatalDay (PND) 0. Litters born after Week 15 were reared until PND21, when all F₀ animals and low- and mid-dose F₁ weanlings werehumanely killed without a necropsy. At PND 74 ± 10, controland high-dose F animals were cohabited within groups for 1 weekand necropsied after delivery of the litters. In F breedingpairs, VCH did not affect measures of reproductive competence,including initial fertility, litters per pair, live litter size,or the proportion of pups born alive. Pup weight was decreased(4%) in the high-dose group relative to controls. High-doseF females exhibited slight general toxic ity, manifested asan 8% difference in body weight compared to controls. VCH didnot adversely affect preweaning growth or survival in the F₁generation. VCH had no effect on the reproductive competenceof the F₁ generation. High-dose F adult males and females haddecreased body weight. At necropsy, in creased relative liverweight (males 9% and females 8%) and sperm motility (althoughnot thought to be biologically significant) were observed inthe 500 mg/kg VCH group. Relative to controls, testicular spermatidcount was decreased by 17% by 500 mg/kg VCH treatment in thepresence of normal epididy mal sperm number and testis and epididymisweight. VCH treated females had significantly reduced numbersof primordial (33% decrease), growing (55% decrease), and antraloocytes(33% decrease) compared to controls, but ovarian weight andestrus cyclicity were unaffected. In summary, VCH, at doseswhich resulted in slight generalized toxicity (500 mg/kg/day),reduced the gamete pool in both the ovary (markedly) and testis(slightly) but had no significant adverse effect on the abilityto reproduce in either the F or F, generation.     

Effects of in utero linuron exposure on rat Wolffian duct development

Linuron is an herbicide that displays weak androgen receptor antagonist activity. Male offspring exposed in utero to 50 mg/kg/day linuron often exhibit malformations in Wolffian duct derivatives (i.e. the epididymis and vas deferens). The objectives of this study were to determine the point during the perinatal period that linuron-induced epididymal lesions can be identified, to characterize linuron-mediated perinatal testicular and epididymal pathology, and to determine whether male rat fetuses exposed prenatally to linuron exhibit decreased intratesticular and serum testosterone (T) levels. Pregnant rats were administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day (n = 3 controls, 5-11 linuron-treated dams per time point) from gestation days (GD) 12 to 21 or to termination. Male fetuses or offspring were necropsied on GD 17, 19, and 21, and postnatal days (PND) 7 and 14. Epididymal malformations were not observed in fetuses from linuron-treated dams but were seen in linuron-exposed male offspring on PND 7 and 14. No testicular lesions were observed at any time point. The growth and development of linuron-exposed fetuses were altered, as evidenced by slight decreases in fetal weight and increased levels of immunoreactive proliferating cell nuclear antigen (PCNA) on GD 21. Intratesticular and serum T levels were not decreased in linuron-exposed male fetuses. These findings indicate that the adversely altered adult phenotype following in utero exposure to linuron is very similar to that produced by the antiandrogens di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP). However, the absence of testicular lesions or alterations in fetal testosterone levels would suggest that the effect of linuron on the developing Wolffian ducts is distinctly different from DBP or DEHP.     

Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis via down-regulation of stress proteins,Fas/Fas-L and caspases expressions in rats

Abstract

This study investigated the protective role of kolaviron, a natural antioxidant biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats were exposed to EGEE (200?mg/kg) separately or in combination with either kolaviron (100 or 200?mg/kg) or vitamin E (50?mg/kg) for 14 days. Immunoblot analysis revealed that EGEE exposure alone significantly increased stress-inducible proteins levels. The increased protein expression of active caspases, Fas and Fas-L, was accompanied by nuclear factor kappa B downregulation and elevation of cytosolic cytochrome c level in EGEE-treated rats. In addition, the observation from immunofluorescence staining was consistent with the increased TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E significantly inhibited induction of stress proteins and germ cell apoptosis in EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti-apoptotic properties prevented EGEE-induced reproductive toxicity in rats.     

Reproductive toxicity of nanoscale graphene oxide in male mice

Abstract

In the past few years, much work has been performed to explore the biomedical applications and toxicity of nano-graphene and its derivatives. However, the reproductive toxicity of those carbon nanomaterials has been rarely studied. In this study, we report on the male reproductive toxicity of nanoscale graphene oxide (GO) using a mouse model. The results showed that the adult male mice injected with high dosages of GO (25?mg/kg mouse) via the tail vein exhibited normal sex hormone secretion and retained normal reproductive activity. All untreated female mice mated with the GO-treated male mice could produce healthy pups. There were no significant differences in pup numbers, sex ratio, weights, pup survival rates or pup growth over time between the GO-treated and control groups. Furthermore, these GO-treated male mice could produce a second, third, fourth and even fifth litter of healthy offspring when they lived with the untreated female mice. The testicular and epididymal histology as well as the activities of several important epididymal enzymes including α-glucosidase, lactate dehydrogenase, glutathione peroxidase and acid phosphatase were not affected by GO treatment. In addition, no damaging effects were seen at high dose rates of GO (total 300?mg/kg male mouse, 60?mg/kg every 24?h for 5 days) via intra-abdominal injection. Thus, GO showed very low or nearly no toxicity for male reproduction. This work will greatly enable future investigations of GO nanosheets for in vivo biomedical applications.     

Protective effects of vitamin A and vitamin E succinate against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced body wasting, hepatomegaly, thymic atrophy, production of reactive oxygen species and DNA damage in C57BL/6J mice

The protective effect of vitamin A and vitamin E succinate against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity and measures of oxidative stress was studied. Ten mice were treated with either vitamin A (50 mg/kg every other day for eight days) or vitamin E succiante (150 mg/kg/day followed by a dose of 40 mg/kg/day for five additional days). Half of each of the above groups of animals received TCDD on day 4. Five mice received corn oil or TCDD alone. After five days of TCDD treatment, antioxidant combination treatment with vitamin A and TCDD or vitamin E succinate and TCDD resulted in a significant reduction in indicators of acute toxicity including the decrease in total body and thymus weight as compared to TCDD alone (P<0.05). The combination treatment produced also a significant reduction in the increase in liver weight as compared to TCDD only (P<0.05). Following one day of treatment with 50 microg TCDD/kg, vitamin A and vitamin E succinate produced a significant decrease in the production of superoxide anion by peritoneal lavage cells (P<0.05) and in DNA-single strand breaks in the same cells (P<0.05) as assessed by the reduction of cytochrome c and the alkaline elution technique, respectively. A significant decrease in DNA-single strand breaks in peritoneal lavage cells was observed following 5 days treatment with 50 microg TCDD/kg (P<0.05). The results indicate a potential role for oxidative stress in the acute toxicity of TCDD and a protective effect for vitamin A and vitamin E succinate in the overall toxicity of TCDD including measures of oxidative stress.     

Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7

Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arteries. The objective of this study was to examine the potential toxicity of synthetic MK-7 in BomTac:NMRI mice and in Sprague-Dawley rats. In an acute oral toxicity test, mice were administered a single oral dose of 2000?mg/kg body weight (limit dose) and no toxicity was observed during the 14-day observation period. In the subchronic oral toxicity test in rats, animals were administered MK-7 for 90 days by gavage at the following doses: 0 (vehicle control, corn oil), 2.5, 5, and 10?mg/kg body weight/day. All generated data, including clinical observations, ophthalmology, clinical pathology, gross necropsy, and histopathology, revealed no compound-related toxicity in rats. Any statistically significant findings in clinical pathology parameters and/or organ weights noted were considered to be within normal biological variability. Therefore, under the conditions of this experiment, the median lethal dose (LD₅₀) of MK-7 after a single oral administration in mice was determined to be greater than the limit dose level of 2000?mg/kg body weight. The no observed adverse effect level (NOAEL) of MK-7, when administered orally to rats for 90 days, was considered to be equal to 10?mg/kg body weight/day, the highest dose tested, based on lack of toxicity during the 90-day study period.     

Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10-50 or PND 50-90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels.The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology.     

Effect of in utero and lactational exposure of triazophos on reproductive system functions in male offsprings,Rattus norvegicus

In the present study, Triazophos (TZ) was used at acceptable daily intake (ADI) to investigate the consequence of prenatal and postnatal exposure on reproductive functions in the male offsprings. Pregnant females were divided into three groups, the first group was orally gavaged with olive oil (control), the second group was administered with 0.01?mg kg^?1 bw of the ADI of TZ from gestation day (GD) 1 until parturition (designated as P group) and the third group was gavaged with the same dose from GD1 to postnatal day (PND) 21 of lactation (marked as P?+?L group). Non-significant reduction occurred in the body weight of pups except at (PND) 35 during which body weight of P?+?L group pups significantly decreased. Male offsprings born to TZ exposed females showed significant changes at maturity (PND 63) in weight of liver, thyroid and testis, alterations in the levels of protein, urea, creatinine in plasma and abnormal levels of cholesterol, phospholipids and lipid peroxidation in testicular homogenate. Gonadal inhibition in TZ exposed progeny was reflected from a significant fall in sperm count, sperm motility, plasma testosterone level and histopathological alterations in testis. Hence, in utero and lactational exposure to ADI level of TZ influences testis development and functions in the male offsprings. Further investigations are suggested with germline studies of offsprings to examine the transgenerational effect of TZ exposure.     

Lipidomics investigation of reversal effect of glycyrrhizin (GL) towards lithocholic acid (LCA)-induced alteration of phospholipid profiles

Context: Glycyrrhizin (GL), the major ingredient isolated from licorice, exerts multiple pharmacological activities.

Objective: To elucidate the protective mechanism of GL towards lithocholic acid (LCA)-induced liver toxicity using lipidomics.

Materials and methods: GL (200?mg/kg) dissolved in corn oil was treated intraperitoneally for 7?d. On the 4th day, 200?mg/kg LCA was used to treat mice (i.p., twice daily) for another 4?d. The protective role of GL towards LCA-induced liver toxicity was investigated through evaluating the liver histology and the activity of alanine transaminase (ALT). The complete lipid profile was employed using UFLC-Triple TOF MS-based lipidomics.

Results: Intraperitoneal (i.p.) administration of 200?mg/kg GL can significantly protect LCA-induced liver damage, indicated by alleviated histology alteration and prevention of the ALT elevation. Lipidomics analysis can well separate the control group from LCA-treated group, and three lipid components were major contributors, including LPC 16:0, LPC 18:0, and LPC 18:2. GL treatment can significantly prevent LCA-induced reduction of these three lipid compounds, providing a new explanation for GL's protection mechanism towards LCA-induced liver toxicity.

Discussion and conclusion: The recent study highlights the importance of lipidomics in elucidating the therapeutic mechanism of herbs.     

Effects of bisphenol A given neonatally on reproductive functions of male rats

Male Sprague-Dawley rats (Crj:CD (IGS) were treated neonatally with bisphenol A (BPA) to evaluate effects on reproductive parameters. Animals were given BPA subcutaneously in corn oil to dosages of 0.002-97 mg/kg body weight, or 0.9 mg/kg 17beta-estradiol (E2) once a day from postnatal day (PND) 0 to PND 9. Preputial separation, copulatory rate, fertility rate, sperm analysis, serum testosterone levels, and gene expression in the testis were assessed. Males in the E2 group showed a decrease in testis weight and alterations of estrogen-mediated gene expression in the testis on PND 10, and by PND 150 incomplete preputial separation, decreases in the copulatory rate, testicular and accessory organ weights and number of sperm. In contrast, males in all BPA groups showed normal reproductive parameters. These results indicate that in male rats, BPA given during the neonatal period neither affected reproductive function nor evoked estrogen-mediated gene responses in the testis.     

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000?mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000?mg/kg body weight, respectively, for five times a week for 90?d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000?mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD₅₀ value of over 2000?mg/kg.     

Developmental toxicity of perfluorooctane sulfonate (PFOS) is not dependent on expression of peroxisome proliferator activated receptor-alpha (PPARα) in the mouse

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of perfluorinated compounds. Both are environmentally persistent and found in the serum of wildlife and humans. PFOS and PFOA are developmentally toxic in laboratory rodents. Exposure to these chemicals in utero delays development and reduces postnatal survival and growth. Exposure to PFOS on the last 4 days of gestation in the rat is sufficient to reduce neonatal survival. PFOS and PFOA are weak agonists of peroxisome proliferator activated receptor-alpha (PPARα). The reduced postnatal survival of neonatal mice exposed to PFOA was recently shown to depend on expression of PPARα. This study used PPARα knockout (KO) and 129S1/SvlmJ wild type (WT) mice to determine if PPARα expression is required for the developmental toxicity of PFOS. After mating overnight, the next day was designated gestation day (GD) 0. WT females were weighed and dosed orally from GD15 to 18 with 0.5% Tween-20, 4.5, 6.5, 8.5, or 10.5 mg PFOS/kg/day. KO females were dosed with 0.5% Tween-20, 8.5 or 10.5 mg PFOS/kg/day. Dams and pups were observed daily and pups were weighed on postnatal day (PND) 1 and PND15. Eye opening was recorded from PND12 to 15. Dams and pups were killed on PND15, body and liver weights recorded, and serum collected. PFOS did not affect maternal weight gain or body or liver weights of the dams on PND15. Neonatal survival (PND1–15) was significantly reduced by PFOS in both WT and KO litters at all doses. WT and KO pup birth weight and weight gain from PND1 to 15 were not significantly affected by PFOS exposure. Relative liver weight of WT and KO pups was significantly increased by the 10.5 mg/kg dose. Eye opening of PFOS-exposed pups was slightly delayed in WT and KO on PND13 or 14, respectively. Because results in WT and KO were comparable, it is concluded that PFOS-induced neonatal lethality and delayed eye opening are not dependent on activation of PPARα.     

Evaluating the protective effects of vitamin E and selenium on hematology and liver,lung and uterus histopathology of rabbits with cypermethrin toxicity

Abstract

The objective of this study was to determine the efficacy of vitamin E and selenium as protective agents against cypermethrin (CY)-induced toxicity by evaluating hematology parameters along with liver, lung and uterus histopathology of female rabbits. Thirty female rabbits were randomly divided into five equal groups with six animals in each group (designated A, B, C, D and E). Animals in group A were control animals that did not receive CY, vitamin E, nor selenium. Animals in groups B–E were injected intraperitoneally with CY at 75?mg/kg body weight once every5 days over a 32?day period, while animals in the control group received saline. Animals in group C were also given vitamin E (150?mg/kg b.wt) orally and animals in group D were given selenium (0.45?mg/kg b.wt) orally. Group E was given both vitamin E at a dose of 150?mg/kg and selenium at a dose of 0.45?mg/kg. In group B (CY only), the values of PCV were decreased at the 12th day of gestation when compared to group A. The mean value of PCV was significantly higher in group E on the 12 and 24th day when compared to the other groups. The mean values of hemoglobin (Hb) were not significantly different among groups on the 12th and 24th day of gestation. On the 12th day of the gestation period, there were nonsignificant differences in the total number of erythrocytes among all the groups. However, on the 24thdayof the gestation period, there was a significant decrease in the total number of erythrocytes in group B compared to the control group. Total leukocytes were also increased in the animals of group B on the 12th day of gestation, whereas the total leukocytes were increased on the 24th day of gestation in all groups (A–D) compared to control. Histopathological studies of tissues of liver, lungs and uterus revealed that CY altered the normal parenchyma of these tissues and this was partially ameliorated by the vitamin E and selenium treatments. In conclusion, combined use of vitamin E and selenium partially ameliorated the toxicity of CY in female rabbits.     

Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T₃ and T₄ in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100 mg/kg body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H₂O₂, hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP.     

Protective effect of crocin on diazinon induced vascular toxicity in subchronic exposure in rat aorta ex-vivo

Abstract

Context: Diazinon (DZN) is a widely used organophosphate insecticide. Although mechanism of DZN cardiovascular toxicity is primarily mediated through inhibition of acetylcholinesterase, however, DZN causes remarkable atropine-insensitive hypotension in rats. It has been proved that oxidative stress is an important mechanism of DZN toxicity especially in chronic exposure. Crocin, an active ingredient of saffron, has been found to antagonize the hypotensive effects of DZN in rats, but do not reverse acetylcholinesterase inhibition. Objective: In this study the effects of DZN on contractile and relaxant responses in rat aorta as well as ex-vivo antioxidant actions of crocin have been investigated. Materials and methods: Rats were divided into 7 groups: corn oil (control), DZN (15?mg/kg/day, gavage), crocin (12.5, 25 and 50?mg/kg/day, i.p.) plus DZN, vitamin E (200?IU/kg, i.p., three days a week) plus DZN and crocin (50?mg/kg/day, i.p.) groups. Treatments were continued for 4 weeks. Contractile and relaxant responses were evaluated on the isolated aorta. Results: Our results showed that DZN not only decreased the contractile responses to KCl and Phenylephrine (PE) (p?<?0.001), but also attenuated the relaxant response to acetylcholine (ACh) (p?<?0.01). Crocin and vitamin E attenuated lipid peroxidation, improved the reduction of contractile responses by KCl and PE and restored the decrease in ACh relaxation in rat aorta. Conclusion: DZN induced vascular toxicity which may be due to oxidative stress and not to a cholinergic mechanism. Crocin improved toxic effects of DZN via reducing lipid peroxidation and restoring altered contractile and relaxant responses in rat aorta.     

A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): effects on androgenic status, developmental landmarks and testicular histology in male offspring rats

An extensive dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) was conducted. A wide range of low and high DEHP doses were tested. Reproductive effects were evaluated on male offspring rats. Female Wistar rats were treated daily with DEHP and peanut oil by gavage from gestation day 6 to lactation day 21 at doses of 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg body weight (bw)/day (low doses) and at 5, 15, 45, 135 and 405 mg DEHP/kg bw/day (high doses). Nipple retention and reduced anogenital distance, both sensitive markers of anti-androgenic effects during development, were only seen in males exposed to the highest dose (405 mg/kg/day). Delayed preputial separation was observed in animals exposed to 15 mg DEHP/kg/day and higher doses. Histopathological examination of the testis on postnatal days (PNDs) 1 and 22 revealed changes at 135 and 405 mg DEHP/kg/day. The most prominent finding on PND 1 was the presence of bi- and multinucleated gonocytes. On PND 22 signs of reduced germ cell differentiation in seminiferous tubules of exposed animals were observed. Testis weight on PND 22 was significantly increased at 5, 15, 45 and 135 mg/kg/day, an effect that qualitatively differs from exposure to higher doses. The current results show that DEHP acts as an anti-androgen at a high dose exposure (405 mg/kg/day). However, these results also indicate that other subtle developmental effects occur at lower DEHP doses.     

Reproductive toxicity of di(2-ethylhexyl) phthalate in selenium-supplemented and selenium-deficient rats

Phthalates are abundantly produced plasticizers, and di(ethylhexyl) phthalate (DEHP) is the most widely used derivative in various consumer products and medical devices. Animal studies show that DEHP and various other phthalates cause reproductive and developmental toxicity. Although the evidences are limited, it seems reasonable that DEHP may have a potential for similar adverse effects in humans. Such concerns are increasing, particularly for the developing reproductive system of male infants and children. By taking into account the essentiality of selenium (Se) in testicular structure and functions and the high prevalence of inadequate Se intake in various part of the world, this study was designed to investigate the testicular toxicity of DEHP in Se-deficient male rats and to examine the possible preventive effects of Se supplementation on phthalate toxicity. Se deficiency was generated by feeding 3-week-old Sprague-Dawley rats with a ≤0.05 Se mg/kg diet for 5 weeks. Supplementation groups were on a 1 mg Se/kg diet, and DEHP-treated groups received a 1,000 mg/kg dose by gavage during the last 10 days of the feeding period. Testicular histopathology, sperm count and motility, and sperm morphology were examined, and plasma levels of sex hormones were measured. Toxicity and antiandrogenic effects of DEHP were evidenced by disturbed testicular histology and spermatogenesis, diminished testosterone, leutinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and sperm motility. The effects of DEHP were much more pronounced in Se-deficient rats, whereas Se supplementation was found to be protective, reflecting its regulating role in cellular redox equilibrium.     

Gestational and lactational exposure to heptachlor does not alter reproductive system development in rats

Like other organochlorine insecticides, heptachlor is lipophilic and accumulates in fatty tissues. Earlier studies suggested that in utero exposure to heptachlor decreased fertility in the offspring; neonatal exposure to the closely related insecticide chlordane reportedly delayed puberty and disrupted estrous cycling in females. We hypothesized that in utero and lactational exposure to heptachlor would disrupt the development of the reproductive system in males and females, resulting in altered timing of puberty and abnormal gonadal histology and reproductive hormone levels. Timed pregnant Sprague-Dawley rats were treated by oral gavage with heptachlor in corn oil at doses of 0.5 and 5.0 mg/kg or an equivalent volume of corn oil alone daily from gestational day 8 through post-natal day (PND) 21, the day of weaning (n = 7-8/group). Litters were standardized to 4 males and 4 females on the day of birth. Two of the dams in the 5.0 mg/kg/d group died. Pups in the highest dose group weighed significantly less than those in the other 2 groups on PND 0. All but 1 litter of the 5.0 mg/kg/d group died within the first 4 post-natal days. Age at eye opening was delayed with increasing heptachlor dose. There was no effect of treatment on pup weight gain in the surviving litters, on anogenital distance, age at puberty, nipple retention past the infantile period in males, estrous cycling, serum sex steroid concentrations, reproductive organ weights, or testicular or ovarian histology. These results suggest that heptachlor exposure during gestation and lactation does not disrupt development of the reproductive system in rats.