Does the Presence of Heavy Metals Influence the Gene Expression and Oxidative Stress in Bladder Cancer?

Heavy metal toxicity is associated with cancer progression. Studies have reported the relation between some metal ions and bladder cancer (BC). Direct influence of such agents in bladder carcinogenesis is still needed. Total 49 BC patients were included in the study. Level of Pb, Cr, Hg and Cd, oxidative stress markers, and gene expression of Bcl-2, Bax, IL-6, AKT, and P38 genes were detected in cancer and non-cancerous tissues obtained from bladder cancer patients. Concentrations of Pb, Cr, and Cd were significantly elevated in cancer tissues than normal, while Hg level was significantly increased in normal tissue than cancer. MDA level was significantly higher and SOD activity was lower in the cancer tissues compared to non-cancerous. The expressions of Bcl-2, IL-6, AKT, and P38 were significantly increased in the cancer tissues than in normal tissues while Bax level was significantly increased in non-cancerous tissue than in cancer tissue. In cancer tissue, there were significant correlations between Cr level with expression of Bax, AKT, and P38 while Cd level was significantly correlate with Bax, IL-6, AKT, and P38expression. The correlation between Cr and Cd with the expression of Bax, IL-6, AKT, and P38 may indicate a carcinogenic role of these metals on progression of bladder cancer.

The Ideal Interval Between Repeated Shockwaves Lithotripsy Sessions for Renal Stones: A Randomized Controlled Trial.

Objectives: To assess the ideal interval between repeated extracorporeal shockwave lithotripsy (SWL) for renal stones. Patient and Methods: Eligible patients with a single renal stone ≤20 mm who required SWL were randomly assigned to one of three groups based on intervals between first and second sessions. Patients underwent the second session after 3, 7, and 14 days in Groups 1, 2, and 3, respectively. Tubular functions were assessed through comparisons of urinary execration of kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), and interleukin-18 (IL-18) with pre-SWL values, whereas glomerular function was assessed by comparisons of protein/creatinine ratio with pre-SWL and changes in ipsilateral renal function on isotope scans. Treatment success was assessed by noncontrast CT after 3 months. Results: All demographics of the 166 patients included in the study were comparable between the three groups. There were significant elevations of tubular biomarkers and protein/creatinine ratio after first and second SWL sessions compared with pre-SWL values (p < 0.0001). All tubular biomarkers returned to pre-SWL values at 7 and 14 days after second session, whereas they remained significantly elevated 3 days after second session (p = 0.027, < 0.001 and <0.001 for KIM-1, NGAL, and IL-18, respectively). SWL success was 73.6% in Group 1, 83.7% in Group 2, and 81% in Group 3. A significant decrease in ipsilateral renal split function was observed in Group 1 at the 3-month follow-up. Conclusions: An interval of 7 days is required between SWL sessions when treating renal stones to allow for complete recovery of kidney functions. Clinical Trial Registration: ID: NCT04575480.

Biogeochemical behaviour and toxicology of chromium in the soil-water-human nexus: A review.

Chromium (Cr) affects human health if it accumulates in organs to elevated concentrations. The toxicity risk of Cr in the ecosphere depends upon the dominant Cr species and their bioavailability in the lithosphere, hydrosphere, and biosphere. However, the soil-water-human nexus that controls the biogeochemical behaviour of Cr and its potential toxicity is not fully understood. This paper synthesizes information on different dimensions of Cr ecotoxicological hazards in the soil and water and their subsequent effects on human health. The various routes of environmental exposure of Cr to humans and other organisms are also discussed. Human exposure to Cr(VI) causes both carcinogenic and non-carcinogenic health effects via complicated reactions that include oxidative stress, chromosomal and DNA damage, and mutagenesis. Chromium(VI) inhalation can cause lung cancer; however, incidences of other types of cancer following Cr(VI) exposure are low but probable. The non-carcinogenic health consequences of Cr(VI) exposure are primarily respiratory and cutaneous. Research on the biogeochemical behaviour of Cr and its toxicological hazards on human and other biological routes is therefore urgently needed to develop a holistic approach to understanding the soil-water-human nexus that controls the toxicological hazards of Cr and its detoxification.

Relation between blood levels of heavy metals and some markers of oxidative stress among boys with neuropathic bladder and posterior urethral valve.

BACKGROUND: The status of heavy metals in children with lower urinary tract pathology that may harm the upper tract, e.g., neuropathic bladder and posterior urethral valve and its relationship with oxidative stress has not been adequately investigated. Therefore, the object of the current work was to evaluate the concentrations of copper, zinc, cadmium and lead and their relations with levels of catalase (CAT), malondialdehyde (MDA) and glutathione (GSH) in boys with neuropathic bladder and posterior urethral valve. METHODS: Thirty-six children with neuropathic bladder, 35 children with posterior urethral valve and 33 health controls were included in the study. In addition to routine laboratory tests, blood samples were collected from patients and controls to assess levels of Cu, Zn, Cd and Pb in addition to plasma concentrations of CAT, MDA and GSH. RESULTS: Significantly elevated levels of Cu, Pb, CAT, MDA and GSH and significantly lower concentration of blood Zn were found in the studied groups compared to the controls. In the posterior urethral valve group, blood level of Cu was positively correlated with GSH while a significantly negative relation was observed between blood Zn and CAT activity among the neuropathic bladder patients. CONCLUSION: Neuropathic bladder and posterior urethral valve may lead to abnormalities in the blood levels of heavy metals (i.e. Cu, Pb and Zn) and markers of oxidative stress (CAT, MDA and GSH). Therefore, the levels of theses metal ions should be monitored during the treatment course of neuropathic bladder and posterior urethral valve patients to prevent or minimize long-term oxidative injury.

Gene expression and oxidative stress markers profile associated with toxic metals in patients with renal cell carcinoma.

BACKGROUND: Toxic metals are associated with cancer progression. Studies have reported the relation between some toxic metals and renal cell carcinoma (RCC). METHODS AND RESULTS: Blood levels of Cd and Pb were determined in 94 RCC patients (RCC group) and 91 matched controls as well as blood level of malondialdehyde (MDA) and catalase (CAT) activity as markers of oxidative stress and antioxidant, respectively. Gene expression of MAP kinase pathway (P38 and JNK), hypoxia-inducible factor 1-alpha (HIF1α), vascular endothelial growth factor (VEGF), cytochrome C oxidase subunit 6 (COX6), metallothionein (MT2A), and heat shock protein (HSP90AA1) were evaluated in the obtained tissue specimens. Blood Cd and Pb levels were significantly higher in RCC group comparing to control group with preferential significant increase of Cd in chromophobe RCC (chRCC) sub-type. MDA level was significantly higher and CAT activity was lower in the RCC compared to controls. The difference was evident only in chRCC. The expressions of genes were significantly increased in the cancer tissues than in non-cancerous tissues in RCC sub-types and there was a significant correlation between Cd levels and expression of genes VEGF, MT2A, P38 and JNK in chRCC group. Immunohistochemical staining of clear cell RCC tissues shows a marked expression of VEGF and HIF-1α.While COX6 staining show marked expression in chRCC. CONCLUSIONS: There is a positive correlation between Cd toxicity and the development of RCC, especially chRCC sub-type. Cd is strongly incriminated in the pathogenesis of chRCC through the effort on some genes and oxidative stress markers.

Correlation between blood levels of cadmium and lead and the expression of microRNA-21 in Egyptian bladder cancer patients.

OBJECTIVE: To investigate the relationship between blood levels of cadmium (Cd) and lead (Pb) and the expression of miRNA-21 among bladder cancer (BC) patients. MATERIAL AND METHODS: The blood concentrations of Cd and Pb in 268 BC patients and 132 controls were determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The blood concentrations of Cd and Pb were interpreted according to the type and stage of the carcinoma. The expression of miRNA-21 was assessed by quantitative reverse transcription polymerase chain reaction in cancerous and adjacent non-cancerous bladder tissues among the patient groups. RESULTS: The blood concentrations of Cd and Pb were statistically elevated in BC patients compared to those of the controls. This elevation is more prevalent in groups with muscle-invasive bladder cancer (MIBC) than those with non-muscle invasive bladder cancer (NMIBC). Among the BC group, miRNA-21 was upregulated in cancerous tissues relative to adjacent non-cancerous tissues. Moreover, the expression was significantly higher in patients with MIBC compared to those with NMIBC. The expression of miRNA-21 in cancerous tissues was significantly associated with blood concentration of Cd and Pb among BC patients. CONCLUSION: There is a relationship between Cd and Pb body burden and the tissue expression of miRNA-21 among BC patients. This indicates the role of miRNA-21 in Cd and Pb induced BC.

Preventive effect of pomegranate juice against chemically induced bladder cancer: An experimental study.

OBJECTIVES: Pomegranate juice (PJ) is rich in important compounds with anti-cancer activities. This study aims to investigate the preventive effect of pomegranate juice (PJ) against bladder cancer (BC). METHODS: Eighty male Sprague Dawley rats were randomly classified into 4 equal groups: (1) Normal controls; (2) PJ group: supplied by PJ for 12 weeks; (3) Cancer-induced group: intake 0.05% v/v N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 8 weeks; (4) Cancer-prevented group: BBN + PJ. After 12 weeks, all rats were sacrificed and their urinary bladder tissues were subjected to histopathological and immunohistochemical (p53) examinations, expression of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor 1 (HIF-1) and the tumor protein p53 (TP53) and analysis of oxidative stress markers. RESULTS: The development of BC was: 0/20 (0%) in normal, PJ and cancer-prevented groups and 20/20 (100%) in cancer-induced group. Significant neoplastic lesions were observed in cancer-induced group. Mild preneoplastic alterations were noticed in 25% (5/20) of cancer-prevented group. p53 immunostaining were significantly elevated in the cancer-induced group, which was decreased in the cancer-prevented group. The relative expressions of IL-6, TNF-α, HIF-1 and TP53 were significantly lower in the cancer-prevented group compared to the cancer-treated group. Correction in the oxidative stress markers were also observed in the cancer-prevented group. CONCLUSION: PJ possesses a promising inhibitory effect on BC development, probably due to its anti-oxidant and anti-inflammatory properties.

Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study.

To evaluate Cu and Zn levels in bladder cancer (BC) patients and their relationship with expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1). Plasma levels of Cu and Zn were determined in 66 transitional bladder cell carcinoma patients (BC group) and 60 matched controls. The concentration of Cu and Zn as well as the expressions of both VEGF and HIF-1 were also estimated in cancerous and non-cancerous bladder tissues in the BC group. The results showed that plasma Cu and Cu/Zn ratio were significantly higher in BC group when compared with the control group. In contrast, the plasma Zn in BC group was significantly lower than in the controls. Comparing levels of Cu and Zn in cancerous and non-cancerous bladder tissues among the BC group indicated a significantly higher Cu levels in the cancerous tissues, while Zn levels was significantly lower. There were higher expressions of both VEGF and HIF-1 in the cancerous samples. Moreover, the Cu concentration in cancerous tissues was significantly correlated with expressions of VEGF and HIF-1. Logistic regression analysis revealed that the increase in plasma Cu/Zn ratio and plasma Cu and the decrease in plasma Zn may be risk factors for development of bladder cancer. We concluded that alteration of plasma and bladder tissue levels of both Cu and Zn is correlated with pathogenesis of bladder cancer. The increase in Cu level in cancerous tissues of BC group has an important role in angiogenesis in bladder cancer cells.

Preconcentration of Lead in Blood and Urine Samples Among Bladder Cancer Patients Using Mesoporous Strontium Titanate Nanoparticles.

In this work, mesoporous strontium titanate nanoparticles (SrTiO3 NPs) were synthesized through a single-step combustion process and were characterized by FT-IR, XRD, SEM-EDX, and TEM. The effects of main parameters that may influence the extraction process (i.e., pH, sorbent amount, time of extraction, eluting agent, and the presence concomitant ions) were investigated. The optimum extraction was achieved at pH 6, 50 mg of sorbent, 20-min shaking time, and 4.0 mL of 0.1 mol L-1 thiourea as desorption agent. Under these conditions, the maximum adsorption capacity was 155.6 mg g-1 with a preconcentration factor of 250 (for a 1000 mL sample solution). The calibration graph was linear up to 1000 µg L-1 and the limit of detection was 1.75 µg L-1. The precision (as relative standard deviation) was 2.53% (n = 10). The procedure was employed for the preconcentration of Pb2+ from blood and urine samples of bladder cancer patients before its determination by FAAS.

Application of Cloud Point Extraction for Cadmium in Biological Samples of Occupationally Exposed Workers: Relation Between Cadmium Exposure and Renal Lesion.

Cadmium (Cd) level in blood and urine of soldering iron workers (n=49) and 41 matched healthy controls has been assessed. Cloud point extraction was employed for preconcentration of Cd. The Cd ions formed hydrophobic complex with 9,10-phenanthraquinone monoethyl thiosemicarbazone that was extracted by surfactant-rich phases in the nonionic surfactant Triton X-114. The surfactant-rich phase was diluted with 1 M HNO3 in methanol prior to its analysis by graphite furnace atomic absorption spectrometry. The parameters affecting the extraction efficiency of the proposed method, such as solution pH, amount of complexing agent, surfactant concentration, temperature, and incubation time, were optimized. Under the optimum experimental conditions, the detection limit and the enrichment factor were 0.04 µg L(-1) and 61, respectively. Relative standard deviation of 10 µg L(-1) Cd was less than 3.0%. The accuracy of the method was examined by analysis of certified reference materials. It was observed that soldering iron workers are liable to Cd overload as indicated by higher levels of Cd in blood and urine when compared with the controls. This exposure may lead to kidney damage indicated by elevation of urinary excretion of both N-acetyl-ß-D-glucosaminidase and ß2-microglobulin.

The exposure to cadmium, lead and mercury from smoking and its impact on renal integrity.

BACKGROUND: Human beings are exposed to cadmium (Cd), lead (Pb) and mercury (Hg) from cigarette smoking. Whether this exposure is associated with nephrotoxicity is unknown. MATERIAL/METHODS: A total of 68 adult males were included in this study. The studied population was grouped into those who are smokers (n=35) and those who had never smoked (n=33). Cd, Pb and Hg were determined in the blood, urine, hair and nails to assess the extent of exposure to these metals. Urinary excretion of b2-microglobulin (b2M), N-acetyl-b-D-glucosaminidase (NAG), g-glutamyltransferase (g-GT) and alkaline phosphatase (ALP) were determined as markers of tubular damage. Albuminuria was determined as a marker of glomerular damage. Serum levels of creatinine, b2M, and blood urea nitrogen (BUN) were determined to assess glomerular filtration. RESULTS: The Cd level in blood and Pb levels in blood and hair were significantly higher in the smokers than non-smokers. Blood levels of Cd and Pb correlated significantly with the smoking index (an indicator for the degree of smoking) in the smokers group. The studied markers of kidney damage neither elevated among the smokers nor correlated with the exposure indices of these metals. CONCLUSIONS: Smokers are exposed to Cd and Pb. This exposure is not high enough to produce nephrotoxicity. However, it may incite signs of nephrotoxicity in the presence of risk factors for kidney diseases.

Reference intervals of cadmium, lead, and mercury in blood, urine, hair, and nails among residents in Mansoura city, Nile delta, Egypt.

A random sample of 68 males and 25 females who reside in Mansoura city, Egypt, was examined for concentrations of cadmium, lead, and mercury in blood, urine, hair, and nails. The effect of gender and smoking on such levels was studied. The influence of dental amalgam on the levels of mercury in these biological samples was also examined. The results obtained show that only blood lead, which increased among males, was affected by gender. Blood levels of cadmium and lead as well as hair lead appeared to increase with smoking habit. Mercury levels in blood and urine were related to the presence of dental amalgam fillings. International comparisons between our results and the corresponding levels in other localities in the world showed that there were environmentally related variations in terms of cadmium levels in hair, lead levels in blood, urine, hair, and nails, and mercury levels in blood, hair, and nails. In conclusion, reference intervals of cadmium, lead, and mercury in the biological samples are environmentally related parameters. Some factors, such as gender, smoking habit, and the presence of dental amalgam fillings, may affect such levels and therefore should be considered.