Protective effect of resveratrol against hexavalent chromium-induced genotoxic damage in Hsd:ICR male mice

It is well-established that exposure to hexavalent chromium [Cr(VI)] induces genotoxic damage. The aim of this study was to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as possible pathways that may be associated with this protection. Hsd:ICR male mice were divided into groups of 5 each and treated as follows: a) control 1, distilled water; b) control 2, ethanol 30%; c) resveratrol, 50 mg/kg by gavage; d) CrO3, 20 mg/kg intraperitoneally; and e) resveratrol in addition to CrO3 (resveratrol+CrO3), with resveratrol administered 4 hr prior to CrO3. The frequency of micronuclei (MN) and cytotoxicity were measured in peripheral blood at 0, 24, 48 and 72 hr, while 8-hydroxydeoxyguanosine (8-OHdG, 7,8-dihydro-8-oxodeoxyguanosine) adduct repair levels, endogenous antioxidant system biomarkers and apoptosis at 48 hr after treatments. Resveratrol administration increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). CrO3 treatment elevated GPx and CAT activities. Resveratrol reduced the frequency of Cr(VI)-induced rise in MN and without significant effect on levels of 8-OHdG adduct when administered alone, suggesting that this polyphenol-mediated cellular repair does not involve 8-OHdG adduct formation. Concomitant administration of resveratrol and Cr(VI)-resulted in return of activities of SOD, GPx and CAT to control levels accompanied by decreased glutathione levels suggesting that the endogenous antioxidant system might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant toxicity. The increase in apoptotic cell number in resveratrol+CrO3 group as well as diminished necrosis further affirms that resveratrol effectively blocked the actions of Cr(VI).

Micronuclei and Nuclear Buds Induced by Cyclophosphamide in Crocodylus moreletii as Useful Biomarkers in Aquatic Environments

Micronuclei (MN) are used to assess genotoxic exposure, whereas nuclear buds (NBs) have been linked to genotoxic events. Crocodylus moreletii was studied to identify MN and NBs. Three groups were formed: Group 1 (water) and groups 2 and 3 (7 or 10 mg/kg of cyclophosphamide). A drop of blood was obtained daily from the claw tip at 0 to 120 h. Spontaneous micronucleated erythrocytes (MNEs) and erythrocytes with nuclear buds (NBEs) were counted. The frequencies of micronucleated young erythrocytes (MNYEs) and NB young erythrocytes (NBYEs) were evaluated, including the ratio of young erythrocytes (YE)/1000 total erythrocytes. No significant differences were observed in the YE proportion on sampling days; group 1 did not show differences for any parameter, whereas group 2 showed significant differences in MNEs and NBEs, and group 3 showed differences in NBEs and NBYEs. Some mitotic activity in circulation was observed in YEs. In conclusion, NBEs could be a more sensitive biomarker to genotoxic damage than MNEs. The identification of these biomarkers leads us to propose Crocodylus moreletii as a possible environment bioindicator because these parameters could be useful to analyze the in vivo health status of these reptiles and for biomonitoring genotoxic pollutants in their habitats.

AgNPs Argovit™ Modulates Cyclophosphamide-Induced Genotoxicity on Peripheral Blood Erythrocytes In Vivo

Silver nanoparticles (AgNPs) have been studied worldwide for their potential biomedical applications. Specifically, they are proposed as a novel alternative for cancer treatment. However, the determination of their cytotoxic and genotoxic effects continues to limit their application. The commercially available silver nanoparticle Argovit™ has shown antineoplastic, antiviral, antibacterial, and tissue regenerative properties, activities triggered by its capacity to promote the overproduction of reactive oxygen species (ROS). Therefore, in this work, we evaluated the genotoxic and cytotoxic potential of the Argovit™ formulation (average size: 35 nm) on BALB/c mice using the micronucleus in a peripheral blood erythrocytes model. Besides, we evaluated the capability of AgNPs to modulate the genotoxic effect induced by cyclophosphamide (CP) after the administration of the oncologic agent. To achieve this, 5–6-week-old male mice with a mean weight of 20.11 ± 2.38 g were treated with water as negative control (Group 1), an single intraperitoneal dose of CP (50 mg/kg of body weight, Group 2), a daily oral dose of AgNPs (6 mg/kg of weight, Group 3) for three consecutive days, or a combination of these treatment schemes: one day of CP doses (50 mg/kg of body weight) followed by three doses of AgNPs (one dose per day, Group 4) and three alternate doses of CP and AgNPs (six days of exposure, Group 5). Blood samples were taken just before the first administration (0 h) and every 24 h for seven days. Our results show that Argovit™ AgNPs induced no significant cytotoxic or acute genotoxic damage. The observed cumulative genotoxic damage in this model could be caused by the accumulation of AgNPs due to administered consecutive doses. Furthermore, the administration of AgNPs after 24 h of CP seems to have a protective effect on bone marrow and reduces by up to 50% the acute genotoxic damage induced by CP. However, this protection is not enough to counteract several doses of CP. To our knowledge, this is the first time that the exceptional chemoprotective capacity produced by a non-cytotoxic silver nanoparticle formulation against CP genotoxic damage has been reported. These findings raise the possibility of using AgNPs as an adjuvant agent with current treatments, reducing adverse effects.

Genotoxic damage evaluation in agricultural workers by exposure to pesticides in Vicente Guerrero-Tlaxcala, Mexico

Pesticides are one of the main inputs in agricultural activities; however, their exposure has been linked to the generation of various health effects. Today, many studies show the ability of pesticides to induce genotoxic damage. The aim of this study was to evaluate the level of genotoxic damage of agricultural workers from Vicente Guerrero-Tlaxcala community, Mexico, exposed to pesticides. The study was composed by 50 agricultural workers from the Vicente Guerrero community and 16 non-exposed individuals. To assess genotoxic damage, the micronucleus (MN) test was applied to exfoliated buccal cell samples by analyzing their frequency and that of other nuclear abnormalities. The agricultural workers showed a frequency of micronucleated cells (P<0,05) and nuclear outbreaks (P<0,05) higher than the control group. The types of pesticides most referred to by the producers were herbicides, belonging to the chemical groups chlorophenoxy and triazine. The exposure time is more than 6 years in more than half of the workers, while the use of personal protective equipment is low. The detected anomalies did not show statistical associations with age, diseases, alcohol, and tobacco consumption. The study revealed that the significant increase in the frequency of MN observed in the exposed group is induced by exposure to pesticides. The application of biomarkers of genotoxicity represents a useful tool to estimate the genetic risk of a population when exposed to a complex mixture of chemicals.