succimer and Urinary-Bladder-Neoplasms

Arsenicosis is a major threat to public health and is a major cause of the development of urinary bladder cancer. Oxidative/ nitrosative stress is one of the key factors for these effects but the involvement of other associated factors is less known. There is a lack of data for the efficacy of chelator against urinary bladder carcinogenesis. The present study demonstrates the early signs of arsenic exposed urinary bladder carcinogenesis and its attenuation by Monoisoamyl dimercaptosuccinic acid (MiADMSA).. Male rats were exposed to 50 ppm of sodium arsenite and dimethylarsinic acid (DMA) via drinking water for 18 weeks and treated with MiADMSA (50 mg/kg, orally once daily for 5 days) for 3 weeks with a gap one week between the two courses of treatments. We compared in vivo data with in vitro by co-exposing 100 nM of sodium arsenite and DMA to rat (NBT-II) as well as human transitional epithelial carcinoma (T-24) cells with 100 nM of MiADMSA.. The data showed that sodium arsenite and DMA exposure significantly increased the tissue arsenic contents, ROS, TBARS levels, catalase, SOD activities and significantly decreased GSH level which might be responsible for an increased 8-OHdG level. These changes might have increased pro-oncogenic biomarkers like MMP-9 and survivin in serum, bladder tissues, NBT-II, and T-24 cells. High cell migration and clonogenic potential in NBT-II and T-24 cells exposed to arsenic suggest pronounced carcinogenic potential. Significant recovery in these biomarkers was noted on treatment with MiADMSA.. Early signs of urinary bladder carcinogenesis were observed in arsenic and DMA exposed rats which were linked to metal accumulation, oxidative/ nitrosative stress, 8-OHdG, MMP-9 and survivin which were reduced by MiADMSA possibly via its efficient chelation abilities in vivo and in vitro.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anticarcinogenic Agents; Arsenites; Cacodylic Acid; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell Transformation, Neoplastic; Chelating Agents; DNA Damage; Humans; Male; Matrix Metalloproteinase 9; Nitrosative Stress; Rats, Sprague-Dawley; Sodium Compounds; Succimer; Survivin; Urinary Bladder Neoplasms

We studied renal anatomy and function using 99mTc-2-3 dimercaptosuccinic acid (DMSA) and 99mTc-diethylenetriaminepentaacetic acid (DTPA) in 27 patients with conduit urinary diversion. In this condition, free ureteral reflux is often associated with bacteriuria, and these factors are thought to precipitate progressive renal deterioration. Gamma-camera images provided valuable information concerning the structure of the renal parenchyma, the function of individual kidneys and possible ureteral obstruction, thus helping us to decide whether or not to instigate further treatment. The information gained using renal gamma imaging with 99mTc-DTPA and 99mTc-DMSA was complementary and partly overlapping. We preferred the use of 99mTc-DTPA because of its ability to visualise the ureters and the region of ureteroconduit anastomosis. Using diuretic medication, we were able to differentiate true ureteral obstruction from atony in 9 patients using 99mTc-DTPA.

Topics: Adult; Aged; Creatinine; Female; Follow-Up Studies; Humans; Ileum; Kidney; Male; Middle Aged; Pentetic Acid; Radioisotope Renography; Risk; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Technetium Tc 99m Pentetate; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urinary Diversion