allopurinol and Kidney-Neoplasms

Antioxidant potentials (AOP) of cancerous and noncancerous adjacent human kidney tissues from 12 patients were measured. AOP of the cancerous tissues was found to be significantly lower than that of noncancerous ones. However, tissue malondialdehyde (MDA) levels were significantly higher in the cancerous tissues compared with noncancerous ones. In the intra-correlation analysis, carried out between AOP and MDA levels, significant correlation was found in the cancerous tissues (r = 0.9) but no correlation observed in the noncancerous ones. In the inter-correlation analysis, negative correlation was found between AOP's of cancerous and noncancerous tissues (r = -0.49) and positive correlation between MDA levels (r = 0.51). Results suggest that antioxidant potential of cancerous kidney tissues is significantly reduced compared with noncancerous ones. Therefore, they expose to high oxidant stress and free radical-induced peroxidative attacks, the results of which are cellular deformations.

Topics: Adult; Aged; Antioxidants; Carcinoma, Renal Cell; Fish Oils; Humans; Kidney Neoplasms; Malondialdehyde; Middle Aged; Xanthine; Xanthine Oxidase

In an effort to identify a new chemopreventive agent, the present study was conducted to investigate the role of T. chebula in the prevention of ferric nitrilotriacetic acid (Fe- NTA) induced oxidative stress and renal tumorigenesis in Wistar rats. A single application of Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) significantly induced oxidative stress and elevated the marker parameters of tumor promotion. However, the pretreatment of animals with different doses of T. chebula extract (25 and 50 mg/kg body weight) restored the levels of reduced glutathione (GSH) and cellular protective enzymes (p < 0.05). Concomitantly, malondialdehyde (MDA) formation and hydrogen peroxide content were also reduced significantly (p < 0.05) at both the doses. The promotion parameters tested (ornithine decarboxylase activity and DNA synthesis) were also significantly suppressed (p < 0.05). T. chebula also inhibited N-diethyl nitrosamine initiated renal carcinogenesis by showing reduction in the number of animals with renal cell tumors and percentage incidence of tumor as compared to the DEN initiated and Fe-NTA promoted rats. The study was further histologically confirmed. These results suggest a potential role of T. chebula in protection from Fe-NTA-induced renal carcinogenesis and oxidative damage.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Carcinogens; Cell Proliferation; Chelating Agents; DNA; Ferric Compounds; Glutathione; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Neoplasms; Lipid Peroxidation; Male; Microsomes; Nitrilotriacetic Acid; Oxidative Stress; Plant Extracts; Quinone Reductases; Rats; Rats, Wistar; Terminalia; Xanthine Oxidase

Ferric nitrilotriacetate (Fe-NTA) is a well-established renal carcinogen. Here, we have shown that Pluchea lanceolata (PL) belonging to the family Asteraceae. PL attenuates Fe-NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. It promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) and renal DNA synthesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) also enhances renal lipid peroxidation (LPO), xanthine oxidase (XO) and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content (GSH), antioxidant enzymes, viz., glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase (QR). It also enhances blood urea nitrogen (BUN) and serum creatinine. Oral treatment of rats with PL extract (100 and 200 mg/kg body weight) resulted in significant decrease in lipid peroxidation (LPO), xanthine oxidase (XO), H(2)O(2) generation, blood urea nitrogen (BUN), serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), its metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, present study supports PL as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rat.

Topics: Animals; Asteraceae; Catalase; Cell Proliferation; Ferric Compounds; Flavonols; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Hydrogen Peroxide; Kidney Neoplasms; Lipid Peroxidation; Male; Neoplasm Staging; Nitrilotriacetic Acid; Ornithine Decarboxylase; Oxidative Stress; Phytotherapy; Plant Extracts; Quinone Reductases; Rats; Rats, Wistar; Xanthine Oxidase

Ferric nitrilotriacetate (Fe-NTA) is a well-known renal carcinogen. In this communication, we show the chemopreventive effect of Ficus racemosa extract against Fe-NTA-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [(3)H] incorporation into renal DNA. It also enhances DEN (N-diethylnitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors. Treatment of rats orally with F. racemosa extract (200 and 400 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumors. Renal glutathione content (P<0.01), glutathione metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant level (P<0.001). Thus, our data suggests that F. racemosa extract is a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rats.

Topics: Animals; Blood Urea Nitrogen; Catalase; Chelating Agents; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Creatinine; Diethylnitrosamine; DNA; Female; Ficus; gamma-Glutamyltransferase; Glutathione; Hydrogen Peroxide; Kidney Neoplasms; Lipid Peroxidation; Microsomes; NAD(P)H Dehydrogenase (Quinone); Nitrilotriacetic Acid; Ornithine Decarboxylase; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Thymidine; Ultraviolet Rays; Xanthine Oxidase

We report the modulatory effect of coumarin (1,2-benzopyrone) on potassium bromate (KBrO(3)) mediated nephrotoxicity in Wistar rats. KBrO(3) (125 mg/kg body weight, i.p.) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [(3)H]-thymidine incorporation into renal DNA. Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01) and antioxidant enzymes were also recovered to significant level (P < 0.001). These results show that coumarin may be used as an effective chemopreventive agent against KBrO(3)-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.

Topics: Animals; Antineoplastic Agents; Blood Urea Nitrogen; Bromates; Catalase; Chemoprevention; Coumarins; Creatinine; DNA; Female; Free Radicals; gamma-Glutamyltransferase; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Hydrogen Peroxide; Kidney; Kidney Neoplasms; Lipid Peroxidation; NAD(P)H Dehydrogenase (Quinone); Ornithine Decarboxylase; Oxidative Stress; Rats; Rats, Wistar; Xanthine Oxidase

In this study, we report the modulatory effect of coumarin (1,2-benzopyrone) on Ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and tumor promotion response in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in antioxidant enzymes and renal glutathione content. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Prophylactic treatment of rats with coumarin (10 and 20 mg/kg body weight) resulted in significant recovery of antioxidant enzymes (P < 0.001) and renal glutathione content (P < 0.01). There was also significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001) Thus, our results show that coumarin is a potent chemopreventive agent and suppresses Fe-NTA induced nephrotoxicity in Wistar rats.

Topics: Animals; Antineoplastic Agents; Antioxidants; Blood Urea Nitrogen; Carcinogens; Coumarins; Creatinine; DNA; Female; Ferric Compounds; gamma-Glutamyltransferase; Glutathione; Hydrogen Peroxide; Kidney; Kidney Neoplasms; Lipid Peroxidation; Nitrilotriacetic Acid; Ornithine Decarboxylase; Oxidative Stress; Rats; Rats, Wistar; Thymidine; Xanthine Oxidase

In this study, activity of some of the key enzymes participating in purine metabolism was measured in cancerous and noncancerous human kidney tissues from 18 patients with renal cell carcinoma. Twelve cancerous tissues were at stage T1-T2 and 6 tissues were at stage T3-T4. Adenosine deaminase (ADA) and guanase (GUA) activity was increased and xanthine oxidase (XO) activity decreased in cancerous tissues compared to noncancerous ones. No difference was, however, found between 5'-Nucleotidase (5'-NT) activity of the tissues. There were also no statistically meaningful differences between the enzyme activities of the cancerous tissues at stage T1-2 and T3-4. Results suggest that the changes observed in the activity of the enzymes participating in purine metabolism result from accelerated DNA turnover in the cancerous tissues and cells, and these changes might provide selective advantage, possibly by causing acceleration of salvage pathway activity, to the cancer cells to grow and develop more rapidly.

Topics: 5'-Nucleotidase; Adenosine Deaminase; Adult; Carcinoma, Renal Cell; DNA; DNA, Neoplasm; Guanine Deaminase; Humans; Kidney; Kidney Neoplasms; Middle Aged; Neoplasm Staging; Purines; Xanthine Oxidase

Bilateral synchronous multifocal Wilms' tumor is a rare malignancy for which no optimum treatment has been established thus far. The need to preserve renal parenchyma whenever possible is obvious. The authors describe a patient who underwent removal of six subcapsular tumors from a kidney that had been protected from ischemia by in situ cooling with UW-Belzer solution and by surface cooling. This technique was safe, easy to perform, and allowed all the time required to resect the tumors under adequate visual control and to wait for analysis of the frozen sections. It might be a useful alternative to the more complicated "bench" technique.

Topics: Adenosine; Allopurinol; Cold Temperature; Glutathione; Humans; Infant; Insulin; Kidney; Kidney Neoplasms; Male; Organ Preservation; Organ Preservation Solutions; Raffinose; Wilms Tumor

We have presented a model for the role of external messenger substances in hypoxic stimulation of kidney production of erythropoietin. These autacoids probably act in concert to activate the adenylate cyclase system to enhance production and/or secretion of erythropoietin. The phosphoproteins generated in this system could act at the level of transcription and translation of erythropoietin as well as at the level of release of erythropoietin from the cell. Even though eicosanoids and beta-2-adrenergic agonists may be involved in mild to moderate hypoxia, it seems more likely that adenosine is more involved in erythropoietin production with increasing severity of hypoxia. Adenosine may play a very early role in hypoxia following the decrease in ATP to trigger erythropoietin production, and hydrogen peroxide may be generated from hypoxanthine, a metabolite of adenosine, during reoxygenation and regional changes in blood flow in the normal kidney and perhaps in certain renal and hepatic tumors. Further work is necessary in vivo to completely clarify the role of adenosine and oxygen free radicals in regulating kidney production of erythropoietin.

Topics: Adenosine; Animals; Carcinoma, Renal Cell; Catalase; Erythropoietin; Female; Glucose Oxidase; Humans; Hydrogen Peroxide; Hypoxanthine; Hypoxanthines; Kidney; Kidney Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Superoxides; Tumor Cells, Cultured; Xanthine Oxidase; Xanthines

The present studies were undertaken to determine the effects of reactive oxygen metabolites on erythropoietin (Ep) biosynthesis in Ep-producing renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Xanthine (10-5M) and increasing concentrations of xanthine oxidase (8 x 10(-7) to 5 x 10(-4) units/ml) produced a significant dose-related increase in Ep production at a concentration of greater than or equal to 4 x 10(-6) units/ml, whereas xanthine alone had no effect. Catalase, a scavenger of hydrogen peroxide (H2O2), in concentrations of 50 to 500 micrograms/ml produced a significant inhibition of the increase in Ep production induced by xanthine-xanthine oxidase; while no effect was seen on basal levels of Ep production and the growth of RC cells. Glucose oxidase (greater than or equal to 0.032 mU/ml), a direct H2O2 generator, and exogenous H2O2 (greater than or equal to 4 x 10(-6)M) added to the incubation mixture, caused a significant enhancement of Ep production in a dose-dependent manner. Xanthine-xanthine oxidase, glucose oxidase, and H2O2 in the above concentrations did not produce significant cytotoxicity (51Cr release or trypan blue dye exclusion). The present data suggests that H2O2, a reactive oxygen metabolite may play a significant role in Ep production.

Topics: Animals; Carcinoma; Catalase; Cell Line; Erythropoietin; Glucose Oxidase; Humans; Hydrogen Peroxide; Kidney Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Oxygen; Xanthine; Xanthine Oxidase; Xanthines

Topics: Animals; Cold Temperature; Dogs; Free Radicals; Humans; Kidney Cortex; Kidney Neoplasms; Kidney Transplantation; Liver; Liver Transplantation; Organ Preservation; Rats; Rats, Inbred Strains; Superoxide Dismutase; Xanthine Oxidase

The paper discusses data on combined T-activin and cytostatic drug treatment of 9 cases of extensive cancer of the kidney and 9 cases of disseminated malignant tumor of the testicle. An immunomodulating effect of T-activin was shown.

Topics: Adjuvants, Immunologic; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Fluorouracil; Humans; Kidney Neoplasms; Male; Peptides; Testicular Neoplasms; Thymus Extracts; Vinblastine

Topics: Adenocarcinoma; Allopurinol; Antineoplastic Agents; Breast Neoplasms; Bronchial Neoplasms; Female; Gout; Humans; Kidney Neoplasms; Lymphoma; Plasmacytoma; Sarcoma; Uric Acid

Topics: Adenocarcinoma; Amidophosphoribosyltransferase; Animals; Cell Differentiation; Cell Transformation, Neoplastic; Gene Expression Regulation; Humans; Kidney Cortex; Kidney Neoplasms; Kinetics; Neoplasms, Experimental; Pentosyltransferases; Rats; Xanthine Oxidase

Topics: Adenocarcinoma; Adult; Allopurinol; Antineoplastic Agents; Calcium; Cyclophosphamide; Fluorouracil; Humans; Hypercalcemia; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Plicamycin; Vincristine