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Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats.

ABSTRACT: Cadmium (Cd) is an environmental toxicant and endocrine disruptor in humans and animals, and recent studies have illustrated that the uterus is exceedingly sensitive to Cd toxicity. The aim of the study was to investigate the influence of subchronic (90 days) oral Cd exposure in daily doses of 0.09-4.5?mg/kg b.w. on the balance of sex hormones by estimating estradiol (E2) and progesterone (P) concentrations in the uterus and plasma in comparison with the effects of 17?-E2. Additionally, the uterine weight, histopathological changes in the uterus and ovaries, the regularity of the estrous cycle, Cd bioaccumulation in uterine tissue, and selected biochemical parameters of oxidative stress were determined. A long period of observation (three and six months following the administration period) was used to assess whether the existing effects are reversible. The lowest dose of Cd caused effects similar to 17?-E2: an increase of E2 concentration in the uterus, endometrial epithelium thickness, and disturbed estrous cycle with estrus phase prolongation. The obtained results suggest that Cd causes nonlinear response. Higher doses of Cd caused a significant decrease in E2 concentration in the uterus and plasma, estrous cycle disturbances, endometrium atrophy, and structural damage in the ovaries. This dose additionally induces lipid peroxidation in the uterine tissues. It is noteworthy that a prolonged time of observation after terminating the exposure showed persistent changes in the concentration of E2 in uterine tissue, as well as alterations in estrous cycle phases, and an increase in lipid peroxidation in the uterus. Moreover, significant positive correlations between the plasma E2 concentration and endometrial epithelium thickness in all studied groups were found. In summary, subchronic oral Cd exposure of female rats may result in impaired fertility processes.

SUBMITTER: Nasiadek M

PROVIDER: S-EPMC6935823 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats.

Nasiadek Marzenna M Danilewicz Marian M Klimczak Michał M Stragierowicz Joanna J Kilanowicz Anna A

Oxidative medicine and cellular longevity 20191217

Cadmium (Cd) is an environmental toxicant and endocrine disruptor in humans and animals, and recent studies have illustrated that the uterus is exceedingly sensitive to Cd toxicity. The aim of the study was to investigate the influence of subchronic (90 days) oral Cd exposure in daily doses of 0.09-4.5 mg/kg b.w. on the balance of sex hormones by estimating estradiol (E2) and progesterone (P) concentrations in the uterus and plasma in comparison with the effects of 17β-E2< ...[more]

PMID: 31949881

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Project description:BackgroundInformation currently available on the impact of palladium on the immune system mainly derives from studies assessing the biological effects of palladium salts. However, in the last years, there has been a notable increase in occupational and environmental levels of fine and ultrafine palladium particles released from automobile catalytic converters, which may play a role in palladium sensitization. In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential.AimTherefore, the aim of this study was to investigate the effects of Pd-NPs on the immune system of female Wistar rats exposed to this xenobiotic for 14 days, by assessing possible quantitative changes in a number of cytokines: IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, GM-CSF, INF-γ and TNF-α.MethodsTwenty rats were randomly divided into four exposure groups and one of control. Animals were given a single tail vein injection of vehicle (control group) and different concentrations of Pd-NPs (0.012, 0.12, 1.2 and 12 μg/kg). A multiplex biometric enzyme linked immunosorbent assay was used to evaluate cytokine serum levels.ResultsThe mean serum concentrations of all cytokines decreased after the administration of 0.012 μg/kg of Pd-NPs, whereas exceeded the control levels at higher exposure doses. The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls.Discussion and conclusionsThese results demonstrated that Pd-NP exposure can affect the immune response of rats inducing a stimulatory action that becomes significant at the highest administered dose. Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the naïve T cells towards Th1 and Th2 phenotype.

Project description:Background:Combretum micranthum (CM) (Combretaceae) is widely used in traditional medicine throughout West Africa for the treatment of diabetes, hypertension, inﬂammation, malaria and liver ailments. In our recent research we demonstrated that CM has nephroprotective potentials in diabetes mellitus, hypertension and renal disorders. However, to the best of our knowledge, no systematic study concerning its toxicity proﬁle has been reported. Aim of the study:The study carried out to evaluates the potential toxicity of the hydroalcoholic extract from leaves of the CM, through the method of acute and sub-chronic oral administration in rats. Materials and methods:During the acute toxicity study, male and female rats were orally administrated with CM extract at single doses of 5000 mg/kg (n = 5/group/sex). Abnormal behaviour, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. For sub-chronic toxicity study, the extract was administered orally at doses of 500 and 1000 mg/kg (n = 5/group/sex) daily to Wistar rats for 28 days. The general behaviour and body weight of the rats was observed daily. A biochemical, haematological, macroscopical and histopathological examinations of several organs were conducted at the end of the treatment period. The CM extract was subjected to Fourier transform infrared spectrophotometric examination in order to detect the presence or absence of cyanide toxic compounds. Results:The absence of absorbance peaks between the 2220-2260 cm-1 region of FT-IR spectrum of CM, indicating the absence of cyanide groups. This suggested that the CM extract may not contain toxic substances. During the acute toxicity test, no mortality or adverse effects were noted at the dose of 5000 mg/kg. In the subchronic study, the CM extract induced no mortality or treatment-related adverse effects with regard to body weight, general behaviour, relative organ weights, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. Conclusion:The present study revealed that oral administration of CM extract for 28 days, at dosage up to 1000 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the extract was estimated to be more than 5000 mg/kg.

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Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats.

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Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats.

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