Exploration of the optimal strategy for dietary calcium intervention against the toxicity of liver and kidney induced by cadmium in mice: An in vivo diet intervention study.

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control.

Protective Effect of Grape and Apple Juices against Cadmium Intoxication in the Kidney of Rats.

BACKGROUND: The objective of this study was to evaluate protective effect of grape and apple juices against toxicity induced by cadmium in the kidney of rats. METHODS: A total of 20 male-Wistar rats were distributed into four groups (n=5): Control group: animals received an intraperitoneal (i.p.) injection of 0.9% saline solution and after 15 days, 1 mL of water was administered for 15 days, via gavage; Cadmium group: animals received an intraperitoneal injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1 mL of water was administered for 15 days via gavage; Cadmium+Grape Juice: animals received an i.p. injection of cadmium chloride (1.2 mg/kg), and after 15 days, 0.8 mL of grape juice was administered for 15 days, via gavage; Cadmium+Apple Juice: animals received i.p. injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1.0 mL of apple juice was administered for 15 days, via gavage. RESULTS: Histopathological analysis revealed severe tubular lesion and necrosis in the group exposed to cadmium, while animals exposed to grape or apple juices showed a significant reduction of tissue injury. 8-OHdG immunoexpression, DNA damage, cytochrome C and catalase gene expressions and Toll like signaling pathway (TLR2, and pIKKα/ß) decreased in animals treated with grape juice when compared to cadmium group. CONCLUSION: Taken together, we conclude that grape and apple juices had a protective effect by means of antioxidant, antigenotoxic actions and for promoting tissue regeneration in the kidney of rats following cadmium intoxication.

Alleviation of cadmium-induced oxidative stress by trehalose via inhibiting the Nrf2-Keap1 signaling pathway in primary rat proximal tubular cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)-induced oxidative stress via Nrf2 antioxidant pathway. Data showed that Tre treatment inhibited Nrf2 nuclear translocation and restored the decline in Kelch-like ECH-associated protein 1 (Keap1) protein level in Cd-exposed rPT cells. Moreover, Cd-activated Nrf2 target genes, including phase II detoxifying enzymes, that is, NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1, direct antioxidant proteins, that is, glutathione peroxidase, superoxide dismutase, catalase, and glutathione biosynthesis-related proteins, that is, glutamatecysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione reductase, were all downregulated by co-treatment with Tre. Collectively, these findings demonstrate that Tre treatment alleviates Cd-induced oxidative stress in rPT cells by inhibiting the Nrf2-Keap1 signaling pathway.

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.

α-Lipoic acid protects against the oxidative stress and cytotoxicity induced by cadmium in HepG2 cells through regenerating glutathione regulated by glutamate-cysteine ligase.

Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). In the present study, we examined the protective effects of α-LA against the oxidative stress and cytotoxicity induced by cadmium in human hepatoma cell lines (HepG2) and investigated if the process was mediated through regenerating GSH. Our results showed that after exposure to 25 µM cadmium for 16 h, there was a significant decrease in the cell viability and glutathione levels and a significant increase in lipid peroxidation (p<0.01) compared with untreated cells. The presence of α-LA significantly attenuated cadmium-induced cytotoxicity and lipid peroxidation, and reversed cellular GSH levels compared with cadmium-treated cells (p<0.05). Compared with the cells treated with cadmium, co-treatment with α-LA and cadmium significantly increased the activities of γ-glutamylcysteine ligase (γ-GCL), the rate limiting enzyme in GSH biosynthesis and the mRNA and the protein levels of γ-GCL catalytic subunit (GCLC) and a modifier subunit (GCLM). In conclusion, our results indicated that α-LA is an effective agent to reduce the oxidative stress and cytotoxicity induced by cadmium by regenerating GSH levels through increasing the activities and the expressions of γ-GCL.

Effective removal of cadmium ions from a simulated gastrointestinal fluid by Lentinus edodes.

Lentinus edodes, a functional food, was evaluated as a potential antidote for adsorption/removal of cadmium ion from simulated gastrointestinal fluids. An adsorption/removal capacity of 65.12 mg/g was achieved by L. edodes in solutions with a pH ranging from 2.5 to 6.0, while little if any adsorption was observed in solutions with a pH under 2.5. In solutions with pH 6.0, 84% of the cadmium adsorption by L. edodes occurred in the first minute. Scanning electronic microscopic examination showed that the cell wall polysaccharides of L. edodes provided a rough sponge-like surface for effective cadmium adsorption. FTIR indicated that the carboxyl, hydroxyl and -NH groups of the cell wall polysaccharides and proteins were the primary functional groups that chemically bind with cadmium ions. The energy dispersive spectrometry further revealed that cation exchange might be attributed to cadmium biosorption. These results suggested that L. edodes was effective for cadmium detoxication, especially in low concentration.

Effect of wheat bran and flaxseed on cadmium effects and retention in rats.

Dietary fiber can affect cadmium (Cd) absorption and toxicity, but the effect appears to depend on the type of dietary fiber. The aim of the present study was to compare the effect of dietary sources containing distinct amounts of soluble and insoluble fiber on Cd absorption, accumulation and toxicity in growing rats. The absorption of essential macrominerals (Ca, P and Mg) was also evaluated. Animals received a nutritionally balanced diet with cellulose (cel - control), wheat bran or flaxseed as the fiber source with 0 or 50 mg Cd kg(-1) diet, during 30 days. Cd exposure reduced body weight gain, feed efficiency ratio, epididymal fat relative weight and liver relative weight, and increased plasma alanine aminotransferase activity in all fiber groups. The apparent Cd absorption was similar among Cd-groups, but the flax-Cd group had a higher hepatic and renal Cd concentration. Cd decreased the absorption of Ca and P, and increased Mg absorption in the wheat bran and flaxseed groups, but not in the cel group. Although the different fiber sources investigated had no effect on Cd toxicity, the major soluble fiber source, flaxseed, increased Cd retention. Thus, caution should be taken in the intake of flaxseed by Cd-exposed populations.

Zinc or magnesium supplementation modulates cd intoxication in blood, kidney, spleen, and bone of rabbits.

The objective of this study was to examine the influence of oral supplementation with Zn or Mg on Cd content in the blood and organs of rabbits exposed to prolonged Cd intoxication. Rabbits were divided into the following groups: Cd group-received orally every day for 4 weeks 10 mg Cd/kg body weight (b.w.), Cd+Zn group and Cd+Mg group-exposed to Cd and supplemented with 20 mg Zn/kg b.w. or 40 mg Mg/kg b.w. 1 h after Cd treatment. Cd content in biological material was determined by atomic absorption spectrophotometry. Blood Cd concentration was determined in all investigated groups at time 0 and after 10, 14, 18, 22, 25, and 28 days, whereas Cd content in the brain, heart, lungs, liver, kidney, spleen, pancreas, skeletal muscle, and bone was determined after 28 days. Blood Cd concentration was significantly increased in all groups from the 14th day of Cd intoxication and lasted till the end of the experiment. Zn or Mg supplementation significantly reduced blood Cd content on the 18th and 25th days. Supplementation with Zn or Mg significantly decreased Cd concentration in the kidney, spleen, and bone and, in addition, Zn reduced Cd content in the brain. Supplementation with Zn or Mg in Cd-intoxicated rabbits caused similar reduction of blood Cd concentration; however, reduction of tissue Cd content was more pronounced in Zn- than in Mg-supplemented group.

[Changes in organ-specific enzymes under the influence of an enriched food ration in experimental cadmium poisoning]. / Promeni v niakoi organospetsifichni enzimi pod vliianie na obogatena khranitelna dazhba pri eksperimentalna kadmieva intoksikatsiia.

During a 3-month experiment is studied the effect of enriched with iron, calcium, phosphorous and vitamin D2 food ration on the changes in the organospecific enzymes in everyday introduction in the organism of experimental animals of cadmium sulfate in dose 1/40 LD50 (7 mg/kg-1). The serum activity of GOT and GPT is traced in dynamics at the end of the first, second and third month, as well as the activity of gamma-GT, LAP and APh in homogenates of liver and kidneys. The changes established in most of the experimental groups and the dates of observation show an increase in the serum and tissue activity of the examined enzymes (GOT, GPT, LAP). The tissue activity of gamma-GT and the quantity of free sulfhydryl groups are decreased in some of the dates of observation (I and III month). Both the isolated effect of cadmium and enriched food ration and their combined effect are discussed.

Nutritional factors in relation to heavy metal toxicants.

An increased environmental exposure to various toxic heavy metals such as lead, cadmium, or mercury seems to be a fact of 20th-century life. But relatively little attention has been paid to the possible implications of sucy exposure for the nutritional status of humans and animals. This review summarizes the information available concerning the effect of various nutritional factors in resistance to metal toxicants and the effect of heavy metal toxicity on nutritional status. In particular, the following questions are considered: 1) Are there any examples of heavy metal toxicity that are potentiated by a nutritional deficiency? 2) Is there any evidence that nutritional deficiency can be caused by heavy metal toxicity? 3) Is there any proof that heavy metal toxicity can be decreased by an excess intake of nutrients: 4) Is there any proof that heavy metal toxicity can be increased by an excess intake of nutrients? The discussion is focused primarily on studies with animal models but, wherever possible, implications for human health are pointed out.