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.

Dietary cadmium chloride impairs shell biomineralization by disrupting the metabolism of the eggshell gland in laying hens.

In this study, we identified cadmium (Cd) as a potential endocrine disruptor that impairs laying performance, egg quality, and eggshell deposition and induces oxidative stress and inflammation in the eggshell glands of laying hens. A total of 480 38-wk-old laying hens were randomly assigned into 5 groups that were fed a basal diet (control) or a basal diet supplemented with Cd (provided as CdCl2·2.5 H2O) at 7.5, 15, 30, and 60 mg Cd per kg feed for 9 wk. The results showed that, when compared with the control group, a low dose of dietary Cd (7.5 mg/kg) had positive effects on egg quality by improving albumen height, Haugh unit, yolk color, and shell thickness at the third or ninth week. However, with the increase in the dose and duration of Cd exposure, the laying performance, egg quality, and activities of eggshell gland antioxidant enzymes (catalase [CAT], glutathione peroxide [GSH-Px]), and ATPase (Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase) deteriorated, and the activity of total nitric oxide synthase (T-NOS) and the level of malondialdehyde (MDA) increased significantly (P < 0.05). The histopathology and real-time quantitative PCR results showed that Cd induced endometrial epithelial cell proliferation accompanied by upregulation of the mRNA levels of progesterone receptor (PgR) and epidermal growth factor receptor (EGFR), downregulation of the mRNA levels of estrogen receptor α (ERα) and interleukin 6 (IL6), and inflammation of the eggshell gland accompanied by significantly increased expression of complement C3 and pro-inflammatory cytokine tumor necrosis factor α (TNFα) (P < 0.05). In addition, the ultrastructure of the eggshell showed that dietary supplementation with 7.5 mg/kg Cd increased the palisade layer and total thickness of the shell, but with the increase in dietary Cd supplementation (30 and 60 mg/kg) the thickness of the palisade layer and mammillary layer decreased significantly (P < 0.05), and the outer surface of the eggshell became rougher. Correspondingly, the expression of calbindin 1 (CALB1), ovocalyxin-32 (OCX-32), ovocalyxin-36 (OCX-36), osteopontin (SPP1), and ovocledidin-17 (OC-17) decreased significantly (P < 0.05) with increasing dietary Cd supplementation. Conclusively, the present study demonstrates that dietary supplementation with Cd negatively affects laying performance, egg quality, and eggshell deposition by disturbing the metabolism of eggshell glands in laying hens but has a positive effect on egg quality at low doses.

Probiotics as a Complementary Therapy in the Model of Cadmium Chloride Toxicity: Crosstalk of ß-Catenin, BDNF, and StAR Signaling Pathways.

Cadmium chloride (CdCl2) is a ubiquitous environmental toxicant that causes a variety of disturbances in biological systems, including brain dysfunction and testicular tissue degeneration. On the other hand, it is supposed that beneficial properties of probiotic bacteria (Lactobacillus and Acidobacillus) are related to their capacity to adhere or bind different targets, thus leading to improved intestinal microbial balance and other benefits to the host. Bearing aforementioned in mind, the present study was undertaken to investigate the protective effect of probiotic supplementation against cadmium chloride-induced brain and testis toxicity in mice model. Animals received Lactobacillus and Acidobacillus either alone or added to folic acid for 1 week before CdCl2 intoxication in a dose of 20 mg/kg BW followed by probiotics (5 × 109) and/or folic acid (12 mg/kg) treatment for 3 weeks. The levels of malondialdehyde (MDA), butyrl choline esterase (BCHE), reduced glutathione (GSH), and total superoxide dismutase (SOD) activities were investigated. Finally, cadmium neurotoxicity was determined by estimating the gene expression of ß-catenin and brain-derived neurotrophic factor (BDNF), as well as estimating the alterations in testicular function by determining acid phosphatase level in addition to steroidogenic acute regulatory protein (StAR) and 17-hydroxy steroid dehydrogenase (17-ß HSD) gene expression. Based on our results, we can conclude that exposure of mice to cadmium chloride resulted in a significant elevation in MDA, BCHE levels accompanied with a significant reduction in GSH and SOD activities compared to the control value. CdCl2 also downregulated the gene expression of ß-catenin and BDNF, as well as acid phosphatase level, in addition to StAR and 17-ß HSD gene expression. These deviated parameters were significantly modulated in the co-treated animals with probiotics compared with the cadmium-treated group. In conclusion, Lactobacillus and folic acid in a mixture with cadmium acted beneficially to an organism, increasing the cadmium excretion in feces, and consequently increasing ß-catenin and BDNF in brain tissue and StAR and 17-ß HSD in testis and improving their functions. Histoarchitecture analysis confirmed these results.

Selenium Supplementation Changes the Ion Profile in the Pancreas of Chickens Treated with Cadmium.

Increasing evidence indicates that selenium (Se) could antagonize metal toxicity, including cadmium (Cd) toxicity. However, the effects of Se on Cd-induced changes in the ion profile in the pancreas of chickens have not been reported. In the present study, 128 Hy-Line brown laying chickens were divided into the control group, Se-treated group, Se/Cd-treated group, and Cd-treated group, and we detected the concentrations of 28 ions in the four groups by inductively coupled plasma mass spectrometry. In the Cd-treated group, the accumulation of Cd in the pancreas was 836.8 times higher that than in the control group (27,353.71 ppb/32.69 ppb). Meanwhile, the Ca, Ti, Fe, Mo, Li, Al, and Pb levels increased and the Cr, Mn, Ni, Cu, Zn, Se, Sr, and Sb levels decreased due to sub-chronic Cd poisoning. The Fe, Mo, Ba, and Pb levels decreased in the Se/Cd-treated group. Our findings suggest that Cd can accumulate in the chicken pancreas and affect the ion profiles, whereas Se can ameliorate the accumulation of Cd and change the ion profiles in the chicken pancreas.

Effects of Nano-zinc on Biochemical Parameters in Cadmium-Exposed Rats.

Cadmium (Cd) is a toxic environmental and occupational pollutant with reported toxic effects on the kidneys, liver, lungs, bones, and the immunity system. Based on its physicochemical similarity to cadmium, zinc (Zn) shows protective effects against cadmium toxicity and cadmium accumulation in the body. Nano-zinc and nano-zinc oxide (ZnO), recently used in foods and pharmaceutical products, can release a great amount of Zn2+ in their environment. This research was carried out to investigate the more potent properties of the metal zinc among sub-acute cadmium intoxicated rats. Seventy-five male Wistar rats were caged in 15 groups. Cadmium chloride (CdCl2) was used in drinking water to induce cadmium toxicity. Different sizes (15, 20, and 30 nm) and doses of nano-zinc particles (3, 10, 100 mg/kg body weight [bw]) were administered solely and simultaneously with CdCl2 (2-5 mg/kg bw) for 28 days. The experimental animals were decapitated, and the biochemical biomarkers (enzymatic and non-enzymatic) were determined in their serum after oral exposure to nano-zinc and cadmium. Statistical analysis was carried out with a one-way ANOVA and t test. P < 0.05 was considered as statistically significant. The haematocrit (HCT) significantly increased and blood coagulation time significantly reduced in the nano-zinc-treated rats. AST, ALT, triglyceride, total cholesterol, LDL, and free fatty acids increased significantly in the cadmium- and nano-zinc-treated rats compared with the controls. However, albumin, total protein, and HDLc significantly decreased in the cadmium- and nano-zinc-treated rats compared with the controls (P < 0.05). It seems that in the oral administration of nano-zinc, the smaller sizes with low doses and the larger sizes with high doses are more toxic than metallic zinc. In a few cases, an inverse dose-dependent relationship was seen as well. This research showed that in spite of larger sizes of zinc, smaller sizes of nano-zinc particles are not suitable for protection against cadmium intoxication.

Selenium-binding protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity.

Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl2-treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and ß-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl2-exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl2, CdCl2, or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.

Grape seed proanthocyanidins protects against cadmium induced oxidative pancreatitis in rats by attenuating oxidative stress, inflammation and apoptosis via Nrf-2/HO-1 signaling.

The present study has been designed and carried out to explore the role of grape seed proanthocyanidins (GSP) in the pancreas of cadmium (Cd)-induced cellular oxidative stress-mediated toxicity in rats. Four groups of healthy rats were given oral doses of Cd (5-mg/kg BW) and to identify the possible mechanism of action of GSP 100-mg/kg BW was selected and was given 90 min before Cd intoxication. The causative molecular and cellular mechanism of Cd was determined using various biochemical assays, histology, western blotting and ELISA. Cd intoxication revealed increased levels of proinflammatory cytokines (TNF-α, IL1ß and IFN-γ), reduced levels of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2 and GLUT-4) along with the enhanced levels of signaling molecules of apoptosis (cleaved Caspase-12/9/8/3) in the pancreas of Cd-intoxicated rats. Results suggested that the treatment with GSP reduced blood glucose level, increased plasma insulin and mitigated oxidative stress-related markers. GSP protects pancreatic tissue by attenuated inflammatory responses and inhibited apoptosis. This uniqueness and absence of any detectable adverse effect of GSP proposes the possibility of using it as an effective protector in the oxidative stress-mediated pancreatic dysfunction in rats.

Effects of phytate on thyroid gland of rats intoxicated with cadmium.

Cadmium (Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were decreased when compared with the control group, while PA-administered groups with Cd showed a significant improvement when compared with the Cd-treated rats only. Serum thyroid stimulating hormone (TSH) level was significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity in rats.

Dietary fucoidan enhance the non-specific immune response and disease resistance in African catfish, Clarias gariepinus, immunosuppressed by cadmium chloride.

Fucoidan is sulfated polysaccharide extracted from seaweed brown algae. This study was designed to evaluate the immunomodulatory effects and disease resistance of dietary fucoidan on catfish, Clarias gariepinus, immunosuppressed by cadmium. Three hundred and sixty African catfish, C. gariepinus, was allocated into six equal groups. The first group served as a control. Groups (F1 and F2) were fed on fucoidan supplemented ration at concentrations of 4 and 6g/kg diet respectively for 21 days. Groups (Cd, CdF1 and CdF2) were subjected throughout the experiment to a sub-lethal concentration of 5ppm cadmium chloride solution and groups (CdF1 and CdF2) were fed on a ration supplemented with fucoidan. Macrophages oxidative burst, phagocytic activity percentages and lymphocytes transformation index were a significant increase in the fucoidan-treated groups (F1 and F2), while serum lysozyme, nitric oxide and bactericidal activity were enhanced only in group (F2) when compared with controls. These parameters as well as absolute lymphocyte count and survival rate were significantly increased in group (CdF2) when compared with cadmium chloride immunosuppressed group (Cd). It could be concluded that the fucoidan can be used as immunostimulant for the farmed African catfish, C. gariepinus as it can improve its resistance to immunosuppressive stressful conditions.

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.

Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-α, interleukin-6 and oxidative status biomarkers in rats: protective effect of curcumin.

UNLABELLED: The present study was designed to investigate the effect of CdCl2-polluted drinking water (40 mg CdCl2/L) on the level of TNF-α and IL-6, as well as oxidative status biomarkers in plasma of rats. The possible protective effect of oral administration of curcumin (50 mg/kg body weight/day) was assessed. Results illustrated that Cd exposure significantly elevated the plasma levels of TNF-α and IL-6 (p<0.001) as compared to normal rats. Also, Cd administration resulted in a significant elevation in the lipid peroxidation and markedly reduction in the activities of SOD and catalase as well as the level of glutathione and total antioxidant capacity in plasma. The co-treatment of Cd with curcumin significantly reduced the levels of TNF-α and IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Negative correlation between IL-6 or TNF-α was and the plasma activities of catalase, SOD and the level of total antioxidant capacity were found in rats exposed to Cd. CONCLUSION: Cadmium toxicity induced the release of TNF-α and IL-6 which is associated with systemic oxidative stress. This may be involved in the mechanism of the Cd toxicity. On the other hand, the findings suggest the curative action of curcumin against Cd toxicity.

The role of organic selenium in cadmium toxicity: effects on broiler performance and health status.

This work was part of a project designed to assess whether organic selenium (Se) can protect against the toxic effects of cadmium (Cd). A total of 300 1-day-old, as hatched, broilers were randomly distributed in four dietary treatments with five replicate pens per treatment. In T1 treatment, broilers were fed a diet with 0.3 mg/kg added Se, as Se-yeast, without added Cd; in T2, broilers were fed a diet with 0.3 mg/kg Se and 10 mg/kg Cd; in T3, broilers were fed a diet with 0.3 mg/kg Se and 100 mg/kg of Cd; and in T4 treatment broilers were fed a diet with 3 mg/kg Se and 100 mg/kg Cd. The Cd was added to diets T2, T3 and T4 as CdCl2. On the 4th and 6th week, two broilers per replicate pen were killed in order to obtain whole blood, liver, kidney and breast samples. Body mass, feed conversion ratio and mortality were assessed and haematological analyses were performed. Se and Cd levels in tissues were analysed by inductively coupled plasma mass spectrometry. Broilers supplemented with 0.3 mg/kg Se can tolerate low levels of Cd added to the diets, as there were no significant negative effects on the examined performance parameters, whereas addition of excess Cd led to an impairment of broilers' performance. Mortality of broilers did not differ between the four dietary treatments at any interval point or the whole period. The examined haematological parameters such as haematocrit, total blood protein concentration, and leukocytes types ranged within physiological values, revealing no negative health effects after simultaneous Cd and Se addition. The present study indicated that Se can help against the negative effects of Cd, but cannot counteract all of its negative effects.

Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats.

The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Protective effect of grapefruit juice on the teratogenic and genotoxic damage induced by cadmium in mice.

In the present study, we injected pregnant mice at Day 7 of gestation with cadmium chloride (CC) (1.5 mg/kg) intraperitoneally and determined its effect on the frequency of fetal malformations at Day 17 of pregnancy. On the same day, we also determined the level of micronucleated polychromatic erythrocytes (MNPEs) and of micronucleated normochromatic erythrocytes (MNNEs) in blood cells of both the mothers and their fetuses. A significant increase in the number of malformations was found, mainly exencephaly, micrognathia, ablephary, microphthalmia, and clubfoot, as well as a significant increase in the amount of MNPEs and MNNEs. In addition, pregnant mice were administered grapefruit juice (GJ) orally from Days 0 to 17 of the experiment (from 200 to 800 µL/g) to evaluate the potential of the juice in preventing the damage induced by CC. We found a dose-dependent decrease in the number of visceral and skeletal malformations, as well as in the number of MNPEs and MNNEs, in both the mothers and their fetuses. Furthermore, we determined the level of DNA oxidation by measuring levels of the adduct 8-hydroxy-2'-deoxyguanosine, and we found a significant increase in such level induced by CC; in contrast, there was a significant decrease when we added GJ. Therefore, the observed teratogenic and genotoxic protection can probably be related with the antioxidant potential of GJ.

The retention of cadmium and selenium influence in fowl and chickens of F1 generation.

The retention of cadmium and selenium influence on Cd retention in the muscle, liver and kidneys of hens, chickens and in eggs was studied. Cadmium (Cd) as cadmium chloride (CdCl(2)) and selenium (Se) as sodium selenite (Na(2)SeO(3)) were added to feed at dosages: group 0-control, group 1-20 mg/kg Cd, group 2-30 mg/kg Cd + 4 mg/kg Se. The birds were exposed to Cd for 8 weeks. Cadmium level in hens and cocks was found highest in the kidneys, followed by the liver and muscle. Se supplementation resulted in Cd increase in the muscle tissue and in the reduction of Cd content in the liver and in significant decrease in the kidneys (p < 0.05). A higher Cd level in the yolk and lower in the white was noted in both experimental groups. Nonsignificant increase of Cd in eggs was noted in experimental groups with Se supplementation. Level of cadmium in organs of 7-day-old chicks hatched from Cd-treated hens in both experimental groups was low but the tendency to accumulate preferentially the Cd in the liver and kidneys was recorded. Supplementation of selenium in hens and cocks was not reflected in the decrease of Cd in these two organs of F(1) chickens but was reflected in increase in the muscle. In spite of relatively high Cd levels in the organs of layers no layer-egg-chickens transfer was observed. It was confirm that kidneys and liver are organs more attacked by dietary cadmium than muscle. Supplementation of low dose of Se resulted in decrease of cadmium deposition in analyzed organs.

Cadmium chloride exposure modifies amino acid daily pattern in the mediobasal hypothalamus in adult male rat.

The present study was conducted to investigate the possible effects of cadmium exposure on the daily pattern of aspartate, glutamate, glutamine, gamma-aminobutyric acid (GABA) and taurine levels in the mediobasal hypothalamus of adult male rats. For this purpose, animals were treated with cadmium at two different exposure doses (25 and 50 mg l(-1) of cadmium chloride, CdCl(2)) in the drinking water for 30 days. Control age-matched rats received CdCl(2)-free water. After the treatment, rats were killed at six different time intervals throughout a 24 h cycle. CdCl(2) exposure modified the amino acid daily pattern, as it decreased aspartate, glutamate, GABA and taurine levels at 12:00 h with both exposure doses employed. In addition, the treatment with 25 mg l(-1) of CdCl(2) induced the appearance of minimal values at 16:00 h and maximal values between 04:00 and 08:00 h for glutamate, and a peak of glutamine content at 20:00 h. The heavy metal also decreased GABA medium levels around the clock in the mediobasal hypothalamus. However, CdCl(2) did not alter the metabolic correlation between glutamate, aspartate, glutamine and GABA observed in control animals. These results suggest that CdCl(2) induced several alterations in aspartate, glutamate, glutamine, GABA and taurine daily pattern in the mediobasal hypothalamus and those changes may be related to alterations in hypothalamic function.

Role of some Egyptian medicinal plants against liver and kidney toxicity induced by cadmium chloride.

The present study was designed to evaluate the protective effect of some local medicinal plants against liver and kidney toxicity induced by cadmium chloride. Methanolic extracts of Acacia nilotica and Retama raetam were used in this study. Furthermore, histopathological and histochemical investigations were done. Cadmium chloride caused a significant increase in serum AST, ALT, ALP, bilirubin, urea, and creatinine, cholesterol, LDL, triglycerides, and HDL levels Administration of Acacia nilotica and Retama raetma significantly inhibit that increase. Cadmium chloride induced a significant decrease in serum total protein, albumin, globulin levels, albumin/globulin ratio, blood SOD, and GPx, while Acacia nilotica and Retama raetam increase. Cadmium chloride caused a significant increase in MDA and NO, while a significant decrease in MDA and NO after Acacia nilotica and Retama raetam administration. These results suggested a beneficial effect of these plant extracts against experimentally-induced hepato- and nephro-toxicity of cadmium, and the possible mechanism of the protective effects may be partly due to the antioxidant activity of these plants.

Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium.

Cadmium (Cd) is a potential pollutant of the environment. It manifests cyto-toxic effects in different organs in animals. In the present study, intraperitoneal injection of CdCl(2) (1mg/kg body weight) increased lipid peroxidation in Swiss mice testes indicating oxidative stress during 5th to 8th week of post-treatment . The enzymatic activity of superoxide dismutase (SOD), catalase (CT) and peroxidase (PD) were significantly decreased over the post-treatment phase in Cd-treated mice testes compared to vehicle controls. Further, ascorbic acid content also declined significantly in Cd-exposed mice testes. Following Cd treatment, a marked increase in sperm abnormality percentage and significant decrease in sperm count was observed. The purpose of the present study was to evaluate the effect of vitamins C and E supplementation on Cd-treated mice testes. Therefore, Cd-treated mice groups were injected with vitamins C and E, separately, to assess the effect of the vitamins in combating Cd-induced cytotoxicity and other manifestations. Supplementation of vitamin C (10mg/kg body weight) and vitamin E (100mg/kg body weight) to Cd-induced mice groups declined lipid peroxidation, increased sperm count profile, depressed the percentage of sperm abnormality, increased the activity of antioxidant enzymes mentioned above and also increased the concentration of ascorbic acid to a measurable extent. The role of vitamins in reducing oxidative stress-related effects on spermatogenesis in Cd-treated Swiss mice testes have been reported.

Effects of diallyl tetrasulfide on cadmium-induced oxidative damage in the liver of rats.

The protective efficacy of diallyl tetrasulfide (DTS) from garlic on liver injury induced by cadmium (Cd) was investigated. In this study, Cd (3 mg/kg body weight) was administered subcutaneously for 3 weeks to induce toxicity. DTS was administered orally (10, 20 and 40 mg/kg body weight) for 3 weeks with subcutaneous (sc) injection of Cd. Cd-induced liver damage was evidenced from increased activities of serum hepatic enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase, with significant elevation of lipid peroxidation indices (thiobarbituric acid reactive substances and hydroperoxides) and protein carbonyl groups in the liver. Rats subjected to Cd toxicity also showed a decline in the levels of total thiols, reduced glutathione (GSH), vitamin C and vitamin E, accompanied by an increased accumulation of Cd, and significantly decreased activities of superoxide dismutase, catalase (CAT), glutathione peroxidase, glutathione-S-transferase (GST), glutathione reductase, and glucose-6-phosphate dehydrogenase in the liver. Administration of DTS at 40 mg/kg body weight significantly normalised the activities of hepatic marker enzymes, compared to other doses of DTS (10 and 20 mg/kg body weight). In addition, DTS (40 mg/kg body weight) significantly reduced the accumulation of Cd and the level of lipid peroxidation, and restored the level of antioxidant defense in the liver. Histological studies also showed that administration of DTS to Cd-treated rats resulted in a marked improvement of hepatocytes morphology with mild portal inflammation. Our results suggest that DTS might play a vital role in protecting Cd-induced oxidative damage in the liver.

Effect of low doses and high homeopathic potencies in normal and cancerous human lymphocytes: an in vitro isopathic study.

OBJECTIVES: Biologic effects of high homeopathic potencies can be studied in cell cultures using cell lines or primary cells. We hypothesized that primary cells would be more apt to respond to high potencies than cell lines, especially cancer cell lines. We set out to investigate the effects of low doses and high homeopathic potencies of cadmium chloride, respectively, in an intoxication model with human primary lymphocytes compared to a human leukemia cell line (Jurkat). DESIGN: Cells were pretreated with either low concentrations (nM-microM) or high potencies (pool 15-20c) of cadmium for 120 hours, following which they were exposed to a toxic treatment with a range of cadmium concentrations (8-80 microM) during 24 hours. Cell viability was eventually assessed by use of the MTS/PES assay. Controls included a vehicle (NaCl 0.9%) for the low concentrations of cadmium or water 15-20c for cadmium 15-20c. A total of 34 experiments were conducted, 23 with low concentrations and 11 with high potencies of cadmium. Data were analyzed by analysis of variance. RESULTS: Pretreatment with low concentrations or high potencies of cadmium significantly increased cell viability in primary lymphocytes after toxic challenge, compared to control cells (mean effect +/- standard error = 19% +/- 0.9% for low concentrations respectively 8% +/- 0.6% for high potencies of cadmium; p < 0.001 in both cases). The pretreatment effect of low doses was significant also in cancerous lymphocytes (4% +/- 0.5%; p < 0.001), albeit weaker than in normal lymphocytes. However, high homeopathic potencies had no effect on cancerous lymphocytes (1% +/- 1.9%; p = 0.45). CONCLUSIONS: High homeopathic potencies exhibit a biologic effect on cell cultures of normal primary lymphocytes. Cancerous lymphocytes (Jurkat), having lost the ability to respond to regulatory signals, seem to be fairly unresponsive to high homeopathic potencies.