| First Author | Ansar S | Year | 1999 |
| Journal | Carcinogenesis | Volume | 20 |
| Issue | 4 | Pages | 599-606 |
| PubMed ID | 10223187 | Mgi Jnum | J:54799 |
| Mgi Id | MGI:1336070 | Doi | 10.1093/carcin/20.4.599 |
| Citation | Ansar S, et al. (1999) Nordihydroguairetic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumour promotion, in mice. Carcinogenesis 20(4):599-606 |
| abstractText | Ferric-nitrilotriacetate (Fe-NTA) is a known renal carcinogen. In the present study, we report the effect of a potent lignin-derived herbal antioxidant, nordihydroguairetic acid (NDGA), against Fe-NTA-mediated tissue toxicity. Fe-NTA (alone) treatment of mice enhances ornithine decarboxylase activity to 259% in liver and 341% in kidney and increases [3H]thymidine incorporation in DNA to 250% in liver and 324% in kidney compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 138 and 123%, respectively, in liver at a higher dose of 2 mg NDGA/day/animal whereas in kidney the reduction was to 118 and 102%, respectively, compared with the corresponding saline-treated controls. In the Fe-NTA (alone)-treated group, a 12% renal tumour incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA-promoted animals, the percentage tumour incidence was increased to 68% as compared with untreated controls. No tumour incidence was recorded in the DEN-initiated, non-promoted group. The administration of NDGA, afforded >80% protection against DEN- and Fe-NTA-mediated renal tissue injury in vivo. Fe-NTA treatment also enhanced hepatic and renal microsomal lipid peroxidation to 170 and 205% of saline-treated controls, respectively, and hydrogen peroxide generation by >2.5-fold in both tissues accompanied by a 51 and 21% decrease in the level of glutathione and 35-48 and 35-50% decrease in the activities of glutathione-metabolizing and antioxidant enzymes in liver and kidney, respectively. These changes were reversed significantly in animals receiving a pre-treatment of NDGA. Our data show that NDGA can abrogate the toxic and tumour-promoting effects of Fe-NTA in liver and kidney of mice and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and tumorigenesis. |
