Evaluation of Blood Oxidant/Antioxidant Changes and Testicular Toxicity after Subacute Exposure to Cadmium in Albino Rats: Therapeutic Effect of Nigella sativa Seed Extracts.

AIM AND OBJECTIVE: Cells and tissues of the body are prone to oxidative damage as a result of an increased level of reactive oxygen species and nitrogen radical beyond the detoxifying ability of the endogenous antioxidant system. This study aimed to evaluate the ameliorative effect of methanolic extracts of Nigella sativa (MENS) against cadmium-induced blood oxidative stress and testicular toxicity in albino rats. MATERIALS AND METHODS: Twenty-five (25) male albino rats, weighing (200 ± 20g), were randomly grouped into five groups (A-E). Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5 mg/kg) only, group C received CdCl2 and low dose MENS (300 mg/kg, oral), group D received CdCl2 and high dose MENS (600 mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200 mg/kg, oral), for 14 days. No treatment was administered to group A (Normal control). The oxidative state of the blood was assessed by measuring the blood levels or activities of MDA, CAT, GSH and SOD; while testicular injury was assessed by measuring serum testosterone level using ELISA. The testes were harvested for histopathological examination. RESULTS: The results showed that cadmium induced a marked elevation in the level of MDA, and a decrease in SOD, CAT and GSH levels or activities (p<0.05 or p<0.01); but no significant alteration in the serum testosterone level was found (p>0.05); Histopathological studies on the testes showed that cadmium significantly induced testicular injury, which was however ameliorated by the seed extract of N. sativa. CONCLUSION: We conclude that N. sativa seed extract is potentially testiculoprotective and attenuates oxidative stress against harmful chemical toxins such as cadmium.

Autophagy Activation by Crepidiastrum Denticulatum Extract Attenuates Environmental Pollutant-Induced Damage in Dermal Fibroblasts.

Pollution-induced skin damage results in oxidative stress; cellular toxicity; inflammation; and, ultimately, premature skin aging. Previous studies suggest that the activation of autophagy can protect oxidation-induced cellular damage and aging-like changes in skin. In order to develop new anti-pollution ingredients, this study screened various kinds of natural extracts to measure their autophagy activation efficacy in cultured dermal fibroblast. The stimulation of autophagy flux by the selected extracts was further confirmed both by the expression of proteins associated with the autophagy signals and by electron microscope. Crepidiastrum denticulatum (CD) extract treated cells showed the highest autophagic vacuole formation in the non-cytotoxic range. The phosphorylation of adenosine monophosphate kinase (AMPK), but not the inhibition of mammalian target of rapamycin (mTOR), was observed by CD-extract treatment. Its anti-pollution effects were further evaluated with model compounds, benzo[a]pyrene (BaP) and cadmium chloride (CdCl2), and a CD extract treatment resulted in both the protection of cytotoxicity and a reduction of proinflammatory cytokines. These results suggest that the autophagy activators can be a new protection regimen for anti-pollution. Therefore, CD extract can be used for anti-inflammatory and anti-pollution cosmetic ingredients.

Optimization, antioxidant properties and GC-MS analysis of Periploca angustifolia polysaccharides and chelation therapy on cadmium-induced toxicity in human HepG2 cells line and rat liver.

The extraction of Periploca polysaccharides (PAPS) was optimized using the response surface methodology. The influence of solvent, liquid-solid ratio and extraction time on polysaccharide yield was evaluated using a full factorial design (23). Also, PAPS extract did not induce a cytotoxic effect on HepG2 cells within the range of tested concentrations (0-250µgmL-1). Herein, the pre-treatment with PAPS extract (100µgmL-1) reduced cell mortality. Furthermore, the in vivo antioxidant activity of PAPS extract was investigated in rats. The oral administration of 250mgkg-1 body weight of PAPS extract administered above a period of 10 weeks to cadmium chloride (CdCl2) induced toxicity in male Wistar rats, markedly decreased the content of MDA and protein damage in liver tissue, and enhanced liver function parameters (ALAT, ASAT and bilirubin), as well as the activities of hepatic antioxidant status (SOD, CAT, GPx and GSH). Finally, the examination of liver histopathology confirmed that PAPS ameliorate the alteration of liver tissue caused by exposition to cadmium.

Acute enhancement of non-rapid eye movement sleep in rats after drinking water contaminated with cadmium chloride.

Cadmium (Cd) is a heavy metal widely used or effused by industries. Serious environmental Cd pollution has been reported over the past two centuries, whereas the mechanisms underlying Cd-mediated diseases are not fully understood. Interestingly, an increase in reactive oxygen species (ROS) after Cd exposure has been shown. Our group has demonstrated that sleep is triggered via accumulation of ROS during neuronal activities, and we thus hypothesize the involvement of Cd poisoning in sleep-wake irregularities. In the present study, we analyzed the effects of Cd intake (1-100 ppm CdCl2 in drinking water) on rats by monitoring sleep encephalograms and locomotor activities. The results demonstrated that 100 ppm CdCl2 administration for 28 h was sufficient to increase non-rapid-eye-movement (non-REM) sleep and reduce locomotor activities during the night (the rat active phase). In contrast, free-running locomotor rhythms under constant dim red light and their re-entrainment to 12:12-h light/dark cycles were intact under chronic (1 month) 100 ppm CdCl2 administrations, suggesting a limited influence on circadian clock movements at this dosage. The relative amount of oxidized glutathione increased in the brain after the 28-h 100 ppm CdCl2 administrations similar to the levels in cultured astrocytes receiving H2O2 or CdCl2 in culture medium. Therefore, we propose Cd-induced sleep as a consequence of oxidative stress. As oxidized glutathione is an endogenous sleep substance, we suggest that Cd rapidly induces sleepiness and influences activity performance by occupying intrinsic sleep-inducing mechanisms. In conclusion, we propose increased non-REM sleep during the active phase as an index of acute Cd exposure.

Antimutagenic activity of wheat polypeptides in human cells exposed to cadmium chloride.

Antimutagenic effects of polypeptides isolated from Triticum kiharae wheat plantule extracts have been studied on human cells exposed to cadmium chloride. The most effective polypeptide Tk-AMP-BP ß -purothionin exhibited higher antimutagenic activity than wheat water extract and another peptide isolated from the same wheat species, Tk-AMP-γ 2 defensin; it also produced a pronounced antioxidant effect. This polypeptide can be used as a preventive agent for reducing the mutagenic potential of some environmental pollutants and for correction of human diseases associated with the defense system defects.

Histological and morphometric effects of CdCl2 and ginger on osteoporosis induced by bilateral ovariectomy in adult albino rats

Cadmium is a widespread environmental pollutant. Low-level environmental cadmium exposure induced osteoporosis especially in postmenopausal women. Ginger is a strong antioxidant that may play an important role in bone formation. The purpose of the present study was to assess the effects of cadmium chloride and ginger on osteoporosis induced by bilateral ovariectomy in adult albino rats. Seventy-two adult albino rat females were used in the present study. They were divided into non-operated groups and operated groups. Cadmium chloride was received at a dose of 3.5 mg/kg daily by subcutaneous injection for 8 weeks, and ginger was fed on a diet containing 5% ginger for 8 weeks. Rats were sacrificed; femurs were dissected out, fixed and decalcified. Serial transverse and longitudinal sections from the diaphysis and metaphysis of femurs were stained by haematoxylin and eosin (H&E) and Masson trichrome stainings and examined using light microscopy. Femurs of Cd-treated, ovariectomized non-treated, and ovariectomized +Cd-treated groups showed histological and morphometric osteoporotic changes that were marked and exaggerated in the ovariectomized +Cd-treated group. Whereas Cd+ginger, ovariectomized +Cd+ginger and ovariectomized+ginger treated groups showed less bone resorption, more bone formation, and improvement in bone structure and morphometric parameters compared to other groups. Cadmium chloride exposure is a risk factor for osteoporosis, especially in postmenopausal women. Ginger effectively ameliorated cadmium and ovariectomy-induced osteoporosis in rats, and is a promising candidate for the prevention and treatment of postmenopausal osteoporosis (AU)

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Toxicity of cadmium and lead in Gallus gallus domesticus assessment of body weight and metal content in tissues after metal dietary supplements.

The influence of dietary cadmium on the accumulation and effects of dietary lead, examined in chicken. This experiment was conducted to investigate the toxic effects of dietary Cd and Pb on chick's body weight and organ, content of the tissues of these two metals was also detected. One day age chicks of Gallus gallus domesticus fed diet supplemented with 25, 50, 100 ppm of Cd, second group exposure to 300, 500, 1000 ppm of Pb in feed daily during 4 weeks. The control groups were fed without supplementation of metals. The concentrations of Cd and Pb resulted in increased of Cd and Pb content in liver, gizzard and muscle. While Cd 100 ppm and Pb 1000 ppm were increased metals content in feather. Body weight of chicks was not influenced by Cd treatment. In contrary Pb treatment was significantly (p < 0.05) decreased body weight of chicks after dietary treatment. On the other hand, Liver weigh in chicks was significantly (p < 0.05) decreased after Cd and Pb treatments.

Taurine attenuates apoptosis in primary liver cells isolated from Atlantic salmon (Salmo salar).

One of the many functions of taurine is to protect cells against oxidation, by protecting mitochondrial integrity and respiration. Taurine metabolism has attracted much attention in fish nutrition due to the fact that as plant ingredients replace fishmeal, dietary taurine has declined. As the endogenous synthesis of taurine might be too low to protect cells against oxidative stress and apoptosis, the present study aimed to test whether taurine may protect liver cells from apoptosis. Liver cells isolated from Atlantic salmon (Salmo salar) were grown in media supplemented with a physiological concentration of taurine (25 (se 0·5) mm) or without any taurine supplementation (14 (se 3) µm) for 3 d. To increase oxidation in the mitochondria and maximise any cellular response of taurine supplementation, 100 µm-CdCl2 was added or not added to the cells at day 3. At day 4, cells were harvested and assessed for viability. As expected, the addition of CdCl2 decreased cell viability without showing any interaction with taurine supplementation. Cells grown in the taurine-supplemented media had lower protein abundance of active caspase-3. In addition, the protein abundance of phosphorylated mitogen-activating phosphokinase (P-p63, P-p42/44 and P-p38) as well as cytochrome P450 were reduced when taurine was added to the media. Cells grown without taurine supplementation had a more condensed chromatin and more smeared DNA, also pointing to a higher apoptosis in these cells. In conclusion, taurine attenuated apoptosis in primary liver cells isolated from Atlantic salmon, and as such, taurine may be conditionally indispensable in Atlantic salmon.

Ovarian toxicity induced by dietary cadmium in hen.

To investigate the toxicity of cadmium (Cd) on female reproduction in birds, this study was conducted to determine the changes in biochemical parameters of serum and ovary tissue caused by dietary cadmium in hens. Ninety 50-day-old hyline white hens were randomly divided into three groups (30 hens per group): a control group was fed with basal diet, a low dose group was fed with basal diet containing 140 mg/kg CdCl(2) and a high dose group was fed with basal diet containing 210 mg/kg CdCl2. After being treated with Cd for 20, 40 and 60 days, ovary and serum samples were collected and examined for Cd content, histological evaluations, malondialdehyde (MDA) content, glutathione peroxidase (GPx) content, activities of superoxide dismutase (SOD), nitric oxide (NO) content, nitric oxide synthase (NOS) activity, and serum estradiol and progestogen levels. The results showed that the content of Cd, MDA, NO and the activity of NOS in ovary and serum were increased (P < 0.05), while the level of GPx and the activity of SOD were decreased (P < 0.05) in low dose and high dose groups. A time- and dose-dependent correlation was observed between serum and ovary tissue cadmium levels. The number of apoptotic cells in the ovary was increased in the Cd treatment group (P < 0.05). Extensive damage was observed in the ovary. The level of estradiol and progestogen in the serum of low dose and high dose groups was decreased significantly (P < 0.05). It indicated that Cd exposure resulted in oxidative damage of hens' ovary tissue by altering antioxidant defense enzyme systems, lipid peroxidation, apoptosis and endocrine disturbance which may be possible underlying reproductive toxicity mechanisms induced by Cd.

[Antimutagenes' protection action in human repair-defected cells].

The action of natural (garlick extract, retinol) and of synthetic (crown-compound) antimutagenes in lymphotytes with gamma-radiation-induced inhibition of DNA-damages repair in cases of Elers-Danlos, syndrom, progeria and gomocystinurea was studied. Antimutagen cells defence from mutagenes was shown at all cases except one: progeria cells treated by retinol. Thus the repair-deficient cells resistance against mutagenes could be increased by antimutagenes.

Pluchea lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity in Swiss albino mice.

Cadmium intoxication induces lipid peroxidation and causes oxidative damage to various tissues by altering antioxidant defence system enzymes. At 24 h after treatment with a single intraperitoneal dose of cadmium chloride (5 mg kg-1), Swiss albino mice showed a significant increase in the levels of malanodialdehyde and xanthine oxidase (P<0.001), and a concomitant depletion of renal glutathione, catalase (P<0.001) and other antioxidant enzymes. CdCl2 also led to a simultaneous increase in micronuclei formation (P<0.001) and chromosomal aberrations (P<0.05) in mouse bone marrow cells. Oral pre-treatment with Pluchea lanceolata extract at doses of 100 and 200 mg kg-1 for 7 consecutive days before CdCl2 intoxication caused a significant reduction in malanodialdehyde formation and xanthine oxidase activity (P<0.001). A significant restoration of the activity of antioxidant defence system enzymes such as catalase, glutathione peroxidase (P<0.05), glutathione-S-transferase and glutathione reductase (P<0.001) was observed. A significant dose-dependent decrease in chromosomal aberrations and micronuclei formation was also observed (P<0.05). The results indicate that pre-treatment with P. lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity by altering antioxidant enzymes and reducing chromatid breaks and micronuclei formation.

Foetal rat lung epithelial (FRLE) cells: partial characterisation and response to pneumotoxins.

Cultured cell lines are routinely used for in vitro toxicity screens, reducing the requirement for animal studies during the development of new pharmaceutical, agrochemical and cosmetic products. The foetal rat lung epithelial (FRLE) cell line was originally derived from alveolar type II cells (ATII) of the lung. The aims of this study were to further characterise FRLE cells and investigate their potential for screening for pneumotoxins. The cells were found to have retained some of the features of their progenitor cells, namely the expression of cytokeratin proteins, specifically cytokeratin 18, and the ability to actively accumulate the non-selective contact herbicide paraquat. However, the cells have lost the ability to synthesise surfactant protein mRNA and no longer contain multiple lamellar bodies. Toxins that damage ATII cells in vivo (cadmium chloride, cobalt chloride and paraquat) were found to induce cytotoxicity in FRLE cells, as did the non-specific pneumotoxin nitrofurantoin, and hydrogen peroxide. However, the cells were less sensitive to the effects of compounds that require metabolic activation (1-nitronaphthalene, coumarin and butylated hydroxytoluene) and the hepatotoxin bromobenzene. Thus, FRLE cells appear to be a good in vitro model for monitoring the potential toxicity to ATII cells and could be used as an initial screen for pneumotoxicity.

Hepatoprotective effect of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium-induced hepatotoxicity in rats.

Lupeol, a pentacyclic triterpene and its ester derivative, lupeol linoleate, were investigated for their possible hepatoprotective effect against cadmium-induced toxicity in rats. Cadmium intoxicated rats showed elevated levels of malondialdehyde (basal and induced), and decreased levels of antioxidants and antioxidising enzymes in the liver. The oral administration of triterpenes (150 mg/kg, once a day for 3 days before injection of cadmium chloride) changed the tissue redox system by scavenging the free radicals and by improving the antioxidant status of the liver. Lupeol linoleate had a better effect on the antioxidant status of the liver, when compared to lupeol.

Cadmium concentrations in the testes, sperm, and spermatids of mice subjected to long-term cadmium chloride exposure.

BACKGROUND: Exposures to cadmium have been reported to reduce male fertility and there are several hypotheses that suggest how reduced male fertility may result from incorporation of cadmium into sperm chromatin. The purpose of this study was to determine whether mice subjected to long-term intraperitoneal cadmium exposure incorporated cadmium into their sperm chromatin. METHODS: Male mice were exposed to 0.1 mg/kg body weight cadmium in the form of CdCl2 via intraperitoneal injection once per week for 4, 10, 26, and 52 weeks and then sacrificed. The cadmium contents of the liver, testes, pooled sperm, and pooled spermatids from dosed and control animals were determined by atomic absorption spectroscopy. Cadmium and zinc contents in individual sperm and spermatid heads were determined by particle-induced x-ray emission. RESULTS: Atomic absorption spectroscopy revealed that although cadmium accumulated in the liver and testes, cadmium was not detected in pooled sperm or spermatid samples down to minimum detectable limits of 0.02 microg/g dry weight. Particle-induced x-ray emission analyses did not show the presence of cadmium in any sperm or spermatid head down to minimum detectable limits of 15 microg/g dry weight. Particle-induced x-ray emission analyses also demonstrated that phosphorus, sulfur, and zinc concentrations in individual sperm and spermatid heads were not altered by exposure to CdCl2. CONCLUSIONS: Because cadmium was not incorporated into sperm chromatin at levels above 0.02 microg/g dry weight, the data cast doubt on hypotheses that suggest that reduced male fertility may result from incorporation of cadmium into sperm chromatin.