Inhibitory effect of nordihydroguaiaretic acid on the frequency of micronuclei induced by methyl methanesulfonate in vivo.

Nordihydroguaiaretic acid (NDGA) is an antioxidant originally obtained from plants of the genus Larrea. This chemical has shown antigenotoxic activity measuring gene mutations and sister-chromatid exchanges. The aim of this investigation was to determine if NDGA is also an antigenotoxic agent and can inhibit the induction of micronucleus (MN) formation by methyl methanesulfonate (MMS) in mouse. The frequency of micronucleated polychromatic erythrocytes (MPE) was scored for 4 days, and a MN induction curve by a single injection of MMS (40 mg/kg) was obtained. The results of this experiment showed that the highest MN incidence was reached at the second day of exposure with a mean of 13.2%+/-1.0. This value is more than 4 times the control mean. Thus, the modulatory study by NDGA was established at a 2-day exposure time using three doses (6.0, 11.0, and 17.0 mg/kg) against the damage induced by 40 mg/kg of MMS. The results of this study showed a significant reduction of the clastogenic damage at the two highest doses, where the inhibitory values corresponded to 62.2% and 66.7%, respectively. With respect to the ratio polychromatic erythrocytes/normochromatic erythrocytes, a marked toxicity was detected with 2 days of MMS exposure; however, the combination of the two high doses of NDGA plus MMS significantly reduced the cytotoxic damage produced by MMS alone.