4-hydroxy-2-nonenal and Carcinoma--Renal-Cell

This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Blood Urea Nitrogen; Carcinogens; Carcinoma, Renal Cell; Creatinine; Curcumin; Diet; Diethylnitrosamine; Dose-Response Relationship, Drug; Ferric Compounds; Kidney Neoplasms; Male; Mice; Nitrilotriacetic Acid; Oxidative Stress

Topics: Aldehydes; Apoptosis; Carcinoma, Renal Cell; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Gangliosides; Humans; In Situ Nick-End Labeling; In Vitro Techniques; Kidney Neoplasms; Oxidative Stress; Reactive Oxygen Species; T-Lymphocytes; Tumor Escape

The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe-NTA in mice.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Antineoplastic Agents; Carcinoma, Renal Cell; Deoxyguanosine; Disease Models, Animal; Electron Spin Resonance Spectroscopy; Female; Ferric Compounds; Fluorescent Antibody Technique, Indirect; Kidney; Kidney Neoplasms; Lipid Peroxidation; Male; Mice; Mutagens; Nitrilotriacetic Acid; Phenylpropionates; Propolis; Thiobarbituric Acid Reactive Substances

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular necrosis associated with lipid peroxidation and oxidative DNA damage that finally leads to a high incidence of renal cell carcinoma in rodents. In the present study, we investigated what kinds of C(2-12) saturated and unsaturated aldehydes and C(7-12) acyloins, metabolites of saturated aldehydes, are produced in the kidney and liver within 24 h after single i.p. administration of 15 mg Fe/kg of Fe-NTA, or after repeated (1 or 3 wk) i.p. administration of 5-10 mg Fe/kg of Fe-NTA. Amounts of twenty one aldehydes and five acyloins were determined by capillary column gas chromatography-negative-ion chemical ionization mass spectrometry with ammonia as reagent gas. Most of the aldehydes and all the acyloins measured revealed a significant dose-dependent increase 1 to 3 h after single administration in the kidney, among which 4-hydroxy-2-nonenal (HNE) showed the highest increase (27.3-fold) and malondialdehyde (MDA) was the most abundant aldehyde (2.40 nmol/100 mg wet tissue). In the liver, however, the increase in aldehydes and acyloins was less prominent. After repeated administration of Fe-NTA, only 9 aldehydes (ethanal; furfural; trans,trans-2,4-heptadienal; nonanal; trans-2,cis-6-nonadienal; HNE; decanal; trans-4,cis-4-decenal; MDA) and 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2-one; 3-hydroxynonan-2-one; 3-hydroxydodecan-2-one) showed a significant increase. Immunohistochemistry further demonstrated an increased amount of HNE-modified and MDA-modified proteins in the renal proximal tubules after repeated Fe-NTA administration. Some of the aldehydes measured such as HNE and MDA are reportedly cytotoxic, genotoxic and mutagenic. Accumulation of these aldehydes may play a role in this renal carcinogenesis model.

Topics: Aldehydes; Animals; Carcinogens; Carcinoma, Renal Cell; Chromatography, Gas; Fatty Alcohols; Ferric Compounds; Immunohistochemistry; Kidney; Kidney Neoplasms; Kinetics; Liver; Male; Malondialdehyde; Nitrilotriacetic Acid; Rats; Rats, Wistar

The levels of the aldehydic lipid peroxidation products 4-hydroxynonenal and malondialdehyde and the levels of adenine nucleotides were measured during anoxia/reoxygenation studies with isolated human renal tubular cells in vitro. Energy depletion of renal cells was demonstrated by the decrease of ATP level. ATP could be restored completely and rapidly during postanoxic reoxygenation. 4-Hydroxynonenal and malondialdehyde levels increased during reoxygenation. In parallel, the breakdown of physiological 4-hydroxynonenal levels was estimated. The 4-hydroxynonenal formation rate was estimated from accumulation and metabolic breakdown rates of this compound.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Aldehydes; Carcinoma, Renal Cell; Cell Hypoxia; Chromatography, High Pressure Liquid; Free Radicals; Humans; Kidney Neoplasms; Kidney Tubules; Lipid Peroxidation; Malondialdehyde; Oxygen

To study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal-cell carcinoma (RCC), we analyzed 35 cases of RCC for 2 parameters of oxidative damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG), a mutation-prone DNA-base-modified product, was measured by means of high-performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4-hydroxy-2-nonenal (HNE)-modified proteins were measured with a polyclonal antibody against HNE-modified proteins. A 54% higher content of 8-OHdG was found in RCC than in the corresponding non-tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non-tumorous kidneys. Immunohistochemistry for HNE-modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non-tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Aldehydes; Antibodies; Carcinoma, Renal Cell; Deoxyguanosine; DNA Damage; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Male; Middle Aged; Neoplasm Proteins; Oxidation-Reduction; Reactive Oxygen Species; Staining and Labeling