Search Results (13)

Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention. Full article

Background/Objectives: In recent years the global incidence of cancer during pregnancy is rising, occurring in 1 out of every 1000 pregnancies. In this regard, the most used chemotherapy drugs to treat cancer are alkylating agents such as cyclophosphamide (Cp). Despite its great efficacy, has been associated with the production of oxidative stress and DNA damage, leading to embryotoxicity, genotoxicity, and teratogenicity in the developing conceptus. Therefore, this study aimed to investigate the protective role of phycobiliproteins (PBP) derived from Arthrospira maxima (spirulina) in reducing Cp-induced embryotoxicity and genotoxicity in pregnant CD1 mice. Methods: Pregnant CD1 mice were divided into five groups: control, Cp 20 mg/kg, and three doses of PBP (50, 100, and 200 mg/kg) + Cp co-treatment. PBP were administered orally from day 6 to 10.5 dpc, followed by a single intraperitoneal dose of Cp on 10.5 dpc. Embryos were collected at 12.5 dpc to assess morphological development and vascular alterations, while maternal DNA damage was evaluated using micronucleus assays and antioxidant enzyme activity in maternal plasma. Results: PBP exhibited a dose-dependent protective effect against Cp-induced damage. The 200 mg/kg PBP dose significantly reduced developmental abnormalities, micronucleated polychromatic erythrocytes, and oxidative stress, (as evidenced by increased SOD and GPx activity). Conclusions: Phycobiliproteins from Arthrospira maxima (spirulina) effectively reduced Cp-induced morphological and vascular alterations in embryos and genotoxicity in pregnant mice. These findings highlight their potential as a complementary therapy to mitigate teratogenic risks during chemotherapy. Further research is needed to optimize dosing and explore clinical applications. Full article

In this study, the physicochemical properties, fatty acid composition, antioxidant activities, and in vitro as well as in vivo toxicological safety of emu oil were investigated. Emu oil was shown to have a low acid and peroxide value, low amounts of carotenoid and phenolic compounds, and high doses of oleic acid and linoleic acid. Furthermore, in a bacterial reverse mutation assay, emu oil demonstrated no change in the amount of revertant colonies for all strains. In a chromosomal assay, no aberrations occurred in any of the emu oil treatment groups (1.25, 2.5, and 5 μg/mL). In the bone marrow micronucleus test, emu oil up to 20 mL/kg showed no significant increase in the incidence of micronucleated polychromatic erythrocytes. Moreover, emu oil up to 19.3 mg/kg body weight did not affect body weight in an acute oral toxicity study. These results are crucial for the adoption of emu oil as an alternative source of edible oil. Full article

The various species that comprise the genus Glycyrrhiza (Licorice) have long been used as oriental herbal medicines in Asian countries. Wongam (WG), which is a new variety of Glycyrrhiza, was developed in Korea to overcome the limitations of low productivity, environmental restrictions, and an insufficient presence of glycyrrhizic acid and liquiritigenin. In this study, we evaluated WG extract’s genotoxicity through an in vitro bacterial reverse mutation (AMES) test, an in vitro chromosome aberration test, and an in vivo mouse bone marrow micronucleus test. In the AMES test, WG extract at concentrations of up to 5000 µg/plate showed no genotoxicity regardless of S9 mix. No chromosome aberrations appeared after 6 h in 1400 µg/mL WG extract regardless of S9 mix or in 1100 µg/mL WG extract after 24 h without S9 mix. Nor was there a significant increase in the number of micronucleated polychromatic erythrocytes to total erythrocytes up to 5000 mg/kg/day for 2 days detected in the micronucleus test. These results confirm that WG extract is safe for use as an herbal medicine, as it precipitates no detectable genotoxic effects. Full article

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects. Full article

There is growing evidence that the accumulation of DNA damage induced by fine particulate matter (PM_2.5) exposure is an underlying mechanism of pulmonary disease onset and progression. However, there is a lack of experimental evidence on whether common factors (age, gender) affect PM_2.5 induced genomic damage. Here, we assessed the DNA damage potency of PM_2.5 using conventional genotoxicity testing in old male and female mice aged 8 and 40 weeks. Mice were intratracheally instilled with diesel exhaust PM_2.5 (DEP, NIST SRM 1650b), twice a week for 4 weeks. Exposure to DEP was not associated with an increase in the frequency of micronucleated polychromatic erythrocytes and did not induce a systemic genotoxic effect in the bone marrow. Meanwhile, the results from the comet assay showed a significant increase in DNA damage in DEP exposed mouse lung specimens. The positive relationship between DEP exposure and DNA damage is stronger in the older than in the younger group. Statistical analysis showed that there was a modifying effect of age on the association between PM_2.5 exposure and DNA damage. Our results suggest that the age factor should be considered to better understand the cellular adverse effects of PM_2.5. Full article

Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of M. alba (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of M. alba for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. M. alba (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (p < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of M. alba (1 g/kg) produced more prominent suppression (p < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (p < 0.05) improvement in the serum antioxidant enzymes levels with M. alba when compared with the challenge group. The lower dose of M. alba extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of M. alba is possibly due to its antioxidant nature. The ability of the M. alba extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy. Full article

Nigella sativa (N. sativa) is a medicinal plant used for its therapeutic pharmacological effects such as anti-inflammatory, antioxidant, anticancer, antidiabetic, and immunomodulation. This study explored the anti-cytotoxic and anti-genotoxic effect of N. sativa through a micronucleus test (MNT) of BALB/c mice peripheral blood. Using 6-to-8-week-old healthy male BALB/c mice, four groups were formed: (1) Control (sterile water), single-dose 2 mg/kg/intraperitoneal (i.p); (2) N. sativa oil, 500 mg/kg/24 h/7 days/i.p; (3) Cisplatin (CP), single-dose 2 mg/kg/subcutaneous (s.c); (4) N. sativa + CP with their respective dosage. When evaluating polychromatic erythrocytes (PCE), a biomarker of cytotoxicity, the group treated with N. sativa + CP experienced an increase in the frequency of PCE, which demonstrated the recovery of bone marrow and modulation of cell proliferation. The analysis of micronucleated polychromatic erythrocytes (MNPCE), an acute genotoxicity biomarker, showed similar frequency of MNPCE within the groups except in CP, but, in the N. sativa + CP group, the frequency of MNPCE decreased and then regulated. Finally, the frequency of micronucleated erythrocytes (MNE), a biomarker of genotoxicity, the supplementation of N. sativa oil did not induce genotoxic damage in this model. Thus, we conclude that N. sativa has both cytoprotective, genoprotective effects and modulates cell proliferation in BALB/c mice. Full article

SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect. Full article

We investigated the effect of extra virgin (EV) olive oil and genetically modified (GM) soybean on DNA, cytogenicity and some antioxidant enzymes in rodents. Forty adult male albino rats were used in this study and divided into four groups. The control group of rodents was fed basal ration only. The second group was given basal ration mixed with EV olive oil (30%). The third group was fed basal ration mixed with GM (15%), and the fourth group survived on a combination of EV olive oil, GM and the basal ration for 65 consecutive days. On day 65, blood samples were collected from each rat for antioxidant enzyme analysis. In the group fed on basal ration mixed with GM soyabean (15%), there was a significant increase in serum level of lipid peroxidation, while glutathione transferase decreased significantly. Interestingly, GM soyabean increased not only the percentage of micronucleated polychromatic erythrocytes (MPCE), but also the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PEC/NEC); however, the amount of DNA and NCE were significantly decreased. Importantly, the combination of EV olive oil and GM soyabean significantly altered the tested parameters towards normal levels. This may suggest an important role for EV olive oil on rodents’ organs and warrants further investigation in humans. Full article

Plants belonging to the genus Opuntia spp. are the most abundant of the Cactaceae family, grown throughout America and the Mediterranean central area. Its fruit, known as cactus pear or prickly pear, is an oval berry grouped in different colors. Some studies have shown its antioxidant activities which may help in preventing chronic pathologies such as diabetes. The purpose of the study was to evaluate the antioxidant capacity of three varieties of prickly pear juice (red-purple, white-green and yellow-orange) in five different concentrations (100, 250, 500, 750, and 1000 mg/mL) by DPPH (1,1-diphenyl-2-picrylhydrazyl radical) colorimetric method, selecting the best variety to determine its anticlastogenic potential against methyl methanesulfonate (MMS). The results indicate that the highest antioxidant was found in the juice of the prickly pear red-purple variety (PPRP), in all concentrations. Its anticlastogenic potential was therefore evaluated with a micronucleus assay. The experiment was run over two weeks. A negative control was included along with a positive control with MMS (40 mg/kg), a group of mice treated with PPRP (25 mL/kg), and three groups with PPRP (in doses of 25, 16.5 and 8.3 mL/kg) plus the mutagen. The PPRP was administered daily by oral gavage and the MMS was injected intraperitoneally five days prior to the end of the experiment. Blood samples were obtained at 0, 24, 48, 72 and 96 h in order to determine the frequency of micronucleated polychromatic erythrocytes (MNPE). The results indicated that PPRP is not a genotoxic agent, on the contrary, it may reduce the number of MNPE. In this regard, the PPRP showed an anticlastogenic effect directly proportional to its concentrations. Thus, the highest protection was obtained with a concentration of 25 mL/kg after 48 h of treatment. Full article

There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition. Full article

The ability of domestic cooking gas to induce hepatotoxicity and clastogenicity in mice was studied. The mice were exposed to domestic gas for twenty-one days at doses of 100 mg/kg, 200 mg/kg and 300 mg/kg respectively. The positive control group of mice were given sodium arsenite intraperitoneously at a dose of 2.5mg/kg body weight. While the negative control group had only distilled water, sodium arsenite significantly (p < 0.05) induced the formation of micronucleated polychromatic erythrocytes (mPCEs), serum and liver gamma glutamyl transferase (γGT) and alkaline phosphatase (AP) activities respectively as compared with the observations made in the negative control group. Similarly, the domestic gas significantly (p<0.05) induced mPCEs formation, serum and liver, γGT and AP activities. The degree of induction was in the order of 100 mg/kg < 200 mg/kg < 300 mg/kg. However, when compared with the positive control group, the domestic cooking gas at the tested doses was not as potent as sodium arsenite in its ability to induce enzyme activity and mPCEs formation. Limited histopathological analysis of liver samples from treated and untreated mice showed distended blood vessels, necrosis and hepatocellular degeneration in the groups treated with high doses of domestic gas or sodium arsenite as compared with the untreated group. Our findings suggest that the domestic cooking gas has some degree of clastogenic and hepatotoxic activities in mice. Health risks may therefore be associated with long-term occupational and / or domestic exposure in humans. Full article