Nordihydroguairetic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumour promotion, in mice

Ferric-nitrilotriacetate (Fe-NTA) is a known renal carcinogen. In the prese nt study, we report the effect of a potent lignin-derived herbal antioxidan t, nordihydroguairetic acid (NDGA), against Fe-NTA-mediated tissue toxicity . Fe-NTA (alone) treatment of mice enhances ornithine decarboxylase activit y to 259 % in liver and 341% in kidney and increases [H-3]thymidine incorpo ration in DNA to 250% in liver and 324% in kidney compared with the corresp onding saline-treated controls, The enhanced ornithine decarboxylase activi ty and DNA synthesis showed a reduction to 138 and 123 %, respectively, in liver at a higher dose of 2 mg MDGA/day/animal whereas in kidney the reduct ion was to 118 and 102%, respectively, compared with the corresponding sali ne-treated controls. In the Fe-NTA (alone)-treated group, a 12% renal tumou r incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated a nd Fe-NTA-promoted animals, the percentage tumour incidence was increased t o 68% as compared with untreated controls. No tumour incidence was recorded in the DEN-initiated, non-promoted group. The administration of NDGA, affo rded >80% protection against DEN- and Fe-NTA-mediated renal tissue injury i n vivo. Fe-NTA treatment also enhanced hepatic and renal microsomal lipid p eroxidation 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% decrea se in the activities of glutathione-metabolizing and antioxidant enzymes in liver and kidney, respectively. These changes were reversed significantly in animals receiving a pretreatment of NDGA, Our data show that NDGA can ab rogate 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 oxidan t-induced tissue injury and tumorigenesis.