Estrogen-induced kidney carcinogenesis in male Syrian hamsters has previously been postulated to be mediated by free radicals generated by redox cycling of catecholestrogen metabolites. As part of our examination of this hypothesis, we have studied the induction of lipid peroxidation and lipid peroxide-derived malondialdehyde (MDA)-DNA adducts in kidney and liver of hamsters treated with single injections of diethylstilbestrol (DES) or with estradiol (E2) implants for various lengths of time. Treatment of hamsters with 50 and 100 mg/kg DES increased concentrations of both lipid hydroperoxides and of MDA-DNA adducts. In hamsters treated with E2 implants for up to 50 days, lipid peroxide levels in liver were double control values 3 h after hormone implantation, and then decreased to plateau values of 30% over controls. Those in kidney rose to 2- to 3-fold above controls 3 days after hormone implantation and then decreased to plateau values of 51% above controls. MDA-DNA adduct levels were two or three times higher than those of controls in liver and kidney of hamsters treated with hormone implants for 3 and 7 days. Renal lipid peroxide concentrations were raised by chronic treatment with E2, but not by weakly carcinogenic estrogens ethinylestradiol or 2-fluoroestradiol. In contrast, MDA-DNA adduct levels were raised by all three steroidal estrogens 3 days after estrogen implantation. The increases in lipid peroxides and in MDA-DNA adducts in estrogen-treated hamsters support a mechanism of carcinogenesis by free radical generation via redox cycling of catcholestrogen metabolites. Lipid peroxides are postulated to play a dual role in estrogen-induced carcinogenesis, (i) as cofactors for cytochrome P450-mediated formation of catecholestrogen metabolites and their redox cycling, and (ii) as precursors of MDA, a DNA adduct-forming endogenous electrophile.

Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI Juice (TNJ) against CCl(4)-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control, placebo and TNJ (6 mL/rat/day) groups. On day 15, animals in the placebo and TNJ groups received 0.25 mL/kg CCl(4) in corn oil once a week for 12 successive weeks. All animals were sacrificed at week 16. Blood and liver were collected for liver function, lipid panel tests, and histological observation. Histopathological examination revealed that liver sections from the TNJ + CCl(4) appeared similar to controls, whereas typical hepatic steatosis was observed in the placebo + CCl(4) group. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were increased in the placebo group compared with the TNJ group. In contrast, high-density lipoprotein (HDL) was increased in the TNJ group and decreased in the placebo group. Thus, TNJ juice appears to protect the liver from chronic exogenous CCl(4) exposures. Such protective mechanisms are supportive evidence for the utility of noni in traditional medicine for liver ailments.

BackgroundNoni (Morinda citrifolia) juice has demonstrated antioxidant activity in vitro and in vivo. To evaluate this activity in humans, noni juice from Tahiti (TNJ) was evaluated in a 30 day, double-blind, and placebo controlled clinical trial with 285 current heavy smokers. Research participants were randomly assigned to three daily treatment groups: 118 mL placebo, 29.5 mL TNJ, and 118 mL TNJ. Plasma superoxide anion radicals (SAR) and lipid hydroperoxide (LOOH) levels were measured pre and post-intervention.ResultsAfter 30 days, mean SAR decreased from 0.26 ± 0.14 to 0.19 ± 0.10 μmol/mL in the 29.5 mL dose group (P < 0.01) and from 0.26 ± 0.22 to 0.18 ± 0.11 μmol/mL in the 118 mL dose group (P < 0.001). LOOH levels decreased from 0.53 ± 0.19 to 0.40 ± 0.10 μmol/mL in the 29.5 mL dose group (P < 0.001) and from 0.55 ± 0.21 to 0.40 ± 0.14 μmol/mL in the 118 mL dose group (P < 0.001). No significant reductions in SAR or LOOH levels were observed in the placebo group.ConclusionThe results suggest an antioxidant activity from noni juice in humans exposed to tobacco smoke, thereby replicating the results found previous chemical and in vivo tests.