Background: Piper auritum Kuntz is an endemic plant from Mexico and Central America, where it is called “hoja santa”, and it is widely used in both local cuisine and traditional medicine. By using the Ames test (strain TA98), we recently demonstrated that ethanol extract from the plant has no mutagenic potential and that it has a significant antimutagenic effect. Objectives/Methods: In the present report, we extended this evaluation by using five strains of the Salmonella/microsome mutagenicity assay. Moreover, we evaluated the mutagenic/antimutagenic potential of the major component of the ethanol extract, safrole, with the TA98 strain and employed docking studies to examine the molecular relationship of safrole with the CYP1A1 isoform. Results: Our results confirmed the absence of mutagenicity in the ethanol plant extract, as well as a concentration-dependent inhibitory effect on the damage induced by benzo[a]pyrene (BaP). With respect to safrole, we also determined that the compound has no mutagenic potential and has a strong inhibitory effect on the damage induced by BaP. Docking and kinetic analysis confirmed the coupling of safrole with the active site of the CYP1A1 enzyme, leading to competitive inhibition. Conclusions: These results suggest that the inhibitory effect on the enzyme activity is one of the possible antimutagenic mechanisms.

Previous studies have shown mouse antigenotoxic and chemopreventive potential with the administration of Citrus paradisi juice (GJ). To evaluate another activity, the aim of the present report was to determine the beneficial effect of GJ on male mouse reproductive damage induced by cadmium chloride (CC). Seven groups of mice were intragastrically (IG) administered for 11 days. A control group was administered purified water daily, three groups were administered GJ daily (4.1, 16.6, and 33.2 µL/g), plus a single administration of CC (3 mg/kg) on the fifth day of the assay, another group was treated daily with 33.2 µL/g GJ, and a positive control group was treated with 3 mg/kg of CC on day 5 of the experiment. The results with the high GJ dose on the CC-treated mice showed a mean reduction of 88% in sperm quality endpoints (viability, motility, malformations) and a 94% sperm concentration increase. With the same dose, we also determined an 81% reduction in the DNA breaking potential and in the number of micronuclei in the spermatids. We also found an 87% decrease in lipoperoxidation and a 68% decrease in protein oxidation with respect to the CC damage, and a strong DPPH scavenging ability. Our results suggest the potential involvement of the GJ antioxidant in the observed effect.