Sub-chronic lead and cadmium co-induce apoptosis protein expression in liver and kidney of rats.

The combined subchronic effects of exposure to lead acetate and cadmium chloride on apoptosis protein expression were detected in the liver and kidney of rats to investigate the hazards of environmentally relevant, low-dose exposure to these compounds. The TUNEL assay showed that there were increased numbers of apoptotic cells. Immunohistochemical tests showed increased numbers of positive cells under Bax and caspase-3 protein detection and decreased Bcl-2 protein. Furthermore, mitochondrial injury and increased numbers of apoptotic cells with condensed nuclei were observed by TEM. These results suggested that low-dose exposure to Pb and Cd can cause significant hepatic and renal apoptosis and finally impair their function. Hepatic and renal apoptosis induced by low-dose exposure is associated with mitochondrial injury and changes in levels of apoptogenic proteins, such as Bcl-2, Bax, and caspase-3.

Effects of mixed subchronic lead acetate and cadmium chloride on bone metabolism in rats.

This study aimed to determine the effects of administering a mixture of subchronic lead acetate (Pb (NO3)2) and cadmium chloride (CdCl2·2.5H2O) on the bone metabolism of rats. A control group and three experimental groups consisted of randomly selected rats. Rats in each experimental group were orally administered with a mixture of Pb (NO3)2 and CdCl2·2.5H2O with the following respective doses for 90 consecutive days: 0 mg/kg body weight b.w. (Group I, to serve as a control), 29.96 mg/kg b.w. (Group II, 29.25 + 0.71), 89.88 mg/kg b.w. (Group III, 87.74 + 2.14), and 269.65 mg/kg b.w. (Group IV, 263.23 + 6.42). Serum osteocalcin (OC) and bone-specific alkaline phosphates (BALP) were considered as bone-formation markers, whereas carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum acted as bone resorption markers. Calcitonin (CT) and parathormone (PTH) were tested as calciotropic hormones markers. The (Ca) and phosphorus (Pi) concentrations in the serum and urine were determined. These results were indicated by a significant (P < 0.05 - P < 0.01) increase in BALP, CTX, and PTH concentrations and decrease in CT and OC concentrations. Moreover, the concentrations of Ca and Pi in the serum were decreased, whereas those in urine increased. Results indicated that the administration of Pb and Cd induced bone metabolism disorders by decreasing bone formation and increasing bone resorption to destroy the hormonal regulation of mineral metabolism as a result of Ca and Pi imbalance.

[Combined effects of sub-chronic exposure to lead and cadmium on physiological and biochemical indexes of blood in SD rats].

OBJECTIVE: The combined subchronic effects of exposure to lead acetate [Pb (NO3)2] and cadmium chloride [CdCl2 x 2.5H2O] on blood physiological and biochemical indexes of rats were detected to investigate the hazards of environmentally relevant, low-dose exposure to these compounds. METHODS: 80 SD rats were randomly divided into three experiment groups and one control group. The rats in the three experiment groups were orally administrated with Pb(NO3)2 and CdCl2 x 2.5H2O combined solution at the doses of 29.96, 89.88 and 269.65 mg/kg for 90 days respectively, and the rats in control group were orally administrated with water. Blood were collected every 30 days to determine physiological and biochemical indexes. RESULTS: In each poisoning groups, WBC, RBC and HGB increased during early experiment period and then decreased. ALT, AST and BU increased all the experiment time. GLU decreased in the experiment time. Compared with control group, TC increase at high-dose poisoning group and TG decrease at low-dose poisoning group. The TP, ALB, GLO and CRE in the poisoning groups were not significantly different from those in the control group. And the hepatic cells and renal tubule epithelial cells showed granular degeneration, vacuolar degeneration and necrosis in poisoning groups. CONCLUSION: Low-dose Pd-Cd combined exposure could significantly change physiological and biochemical indexes of blood and cause hepatic and renal pathological injury of SD rats.

Effects of subchronic exposure to lead acetate and cadmium chloride on rat's bone: Ca and Pi contents, bone density, and histopathological evaluation.

This study aims to investigate the effects of low-dose subchronic exposure to lead acetate (Pb(NO3)2) and cadmium chloride (CdCl2·2.5H2O) on bone in rats. The rats were assigned randomly to a control group and three experimental groups that were given the mixture of Pb(NO3)2 and CdCl2·2.5H2O by gastric gavage at doses of 0 mg/kg body weight (b.w.) (Group I, to serve as a control), 29.96 mg/kg b.w. (Group II, 29.25+0.71), 89.88 mg/kg b.w. (Group III, 87.74+2.14), and 269.65 mg/kg b.w. (Group IV, 263.23+6.42) for at least 90 consecutive days. Calcium (Ca) and phosphorus (Pi) contents in the bone were determined. Bone mineral density (BMD) was measured at the tibia and femur region by dual-energy X-ray absorbsiometry. The histopathology of bone was evaluated by light microscope, scanning electron microscope, and transmission electron microscope. The BMD of rats in the experimental group was significantly lower and the contents of Ca and Pi were decreased than those in the control group. The histopathological evaluation showed that co-induction of Pb and Cd results in bone microstructure damage, especially to trabecular bone, marrow cavity, collagen fiber, and osteoblast. In general, results indicate that combining Pb with Cd induces bone damage and increases the risk of osteoporosis.

Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days.

Quantification of metallothionein on the liver and kidney of rats by subchronic lead and cadmium in combination.

The combined subchronic effects of exposure to lead acetate and cadmium chloride on oxidative stress and metallothionein (MT) gene expression were detected in the liver and kidney of rats to investigate the hazards of environmentally relevant, low-dose exposure to these compounds. Pb and Cd co-induced oxidative stress in liver and kidney tissues. This result was indicated by a significant (P<0.01) increase in the maleic dialdehyde level and decreased levels of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. MT mRNA and protein significantly increased (P<0.01) in the liver and kidney of rats. Furthermore, the expression levels of MT-1 mRNA and MT-2 mRNA differed between the liver and kidney. The findings indicate that Pb combined with Cd induced oxidative damage in the liver and kidney of rats, and MT may be a biochemical environmental indicator.

Antiviral activity of sulfated Chuanmingshen violaceum polysaccharide against Newcastle disease virus.

Newcastle disease virus (NDV) is a member of Paramyxovirinae subfamily and can infect most species of birds causing severe economic losses. The current control measure is vaccination, but infections cannot be completely prevented. It remains a constant threat to the poultry industry and new control measures are urgently needed. This study demonstrates that sulfated Chuanmingshen violaceum polysaccharides (sCVPSs) were potent inhibitors of NDV, with 50 % inhibitory concentrations (IC50) ranging from 62.55 to 76.31 µg ml(-1) in Baby hamster kidney fibroblasts clone 21 (BHK-21) and from 101.57 to 125.90 µg ml(-1) in chicken embryo fibroblasts (CEF). sCVPS is more effective than heparan sulfate (HS; as a positive control) with IC50 values of 99.28 µg ml(-1) in BHK-21 and 118.79 µg ml(-1) in CEF. sCVPSs and HS exhibit anti-NDV activity by prevention of the early stages of viral life. The mechanism of action study indicated that virus adsorption in BHK-21, and both virus adsorption and penetration in CEF were inhibited by sCVPSs. When the number of viruses was increased to an m.o.i. of 0.1 in the immunofluorescence study and to an m.o.i. of 1 in the fluorescent quantitative PCR study, viral infection was also significantly suppressed; the antiviral activity of sCVPSs was independent of the m.o.i. sCVPSs also prevented the cell-to-cell spread of NDV. In vivo tests carried out on specific pathogen-free (SPF) chickens showed that sCVPSs also inhibited virus multiplication in heart, liver, spleen, lung and kidney. These results indicated that sCVPSs perform more effectively than HS as antiviral agents against NDV, and can be further examined for their potential as an alternative control measure for NDV infection.

Inhibitory effect of resveratrol against duck enteritis virus in vitro.

Duck viral enteritis (DVE) is an acute, contagious herpesvirus infection of ducks, geese, and swans of all ages and species. This disease has been responsible for significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production. Resveratrol is a naturally occurring phytoalexin in specific plants and exhibits inhibitory activity against many kinds of virus. In this paper, resveratrol was found to inhibit duck enteritis virus (DEV) replication in a dose-dependent manner, with a 50% inhibition concentration of 3.85 µg/mL. The inhibition in virus multiplication in the presence of resveratrol was not attributed to direct inactivation or inhibition of virus attachment to the host cells, but to the inhibition of viral multiplication in host cells. The assay of the time of addition limited the drug effect during the first 8 h of infection. This conclusion was supported by the ultrastructure images of the early stage of DEV infection, which showed that the replication of virus nucleic acid and the formation of the capsid in the cell nucleus were suppressed. In the indirect immunofluorescence assay, proteins expression in DEV infected duck embryo fibroblasts (DEFs) within 24 h post-infection (p.i.) was also effectively suppressed by resveratrol. In summary, the resveratrol has a good activity against DEV infection in vitro, which could be attributed to that fact that several essential immediate early viral proteins for virus replication were impacted by resveratrol.