New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice.

Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did not show permanent damage, observed by the absence of increased micronucleus frequency, and did not induce changes in the biometric parameters of the animals. These results indicate that the new copper complex, described firstly in this work, presents therapeutic potential for breast cancer.

Evaluation of the effects of the larvicides temephos on reproductive performance, embryofetal development and DNA integrity of Swiss mice.

Temephos is considered the gold standard by the Ministry of Health for controlling the larvae of the mosquito Aedes aegypti. The present study evaluated the effects of Temephos larvicide on the reproductive performance, embryo-fetal development and DNA integrity of Swiss mice. This study used 30 pregnant female mice: 10 were controls treated with drinking water at a dosage of 0.1 mL/10 g (body weight - b.w., administered orally - a.o.), and 20 were treated with Temephos at doses of 0.0043 mg/kg and 0.043 mg/kg (b.w., a.o.) during the gestational period. Statistical analysis showed that Temephos did not alter the biometric or reproductive parameters. Comparing the weight of the fetus to the stage of pregnancy demonstrated that the 0.0043 mg/kg dosage increased the size of the fetuses. No external malformations were detected. However, the 0.043 mg/kg dosage induced changes in the sternum, with the main change being the center of the sternum, xiphoid processes and absence of the manubrium. The other skeletal and visceral alterations did not differ from the control group and are considered variants of normality. The analysis of head measurements showed an increase in the anterior/posterior measurements of the glabella, the external occipital protuberance and the biauricular plane. The circumference and area of the head did not present significant differences. The micronucleus test showed only a 0.043 mg/kg increase in 48 h. Thus, it is considered that Temephos has a low teratogenic and genotoxic risk.

Evaluation of the toxicokinetics and apoptotic potential of ethanol extract from Echinodorus macrophyllus leaves in vivo.

This study evaluates the toxicological, genotoxic, mutagenic and apoptotic potential of an in vivo assay from Echinodorus macrophyllus extract (EEM). The acute toxicity test used 02 groups (n = 5) of female Wistar rats: negative control group (saline) and experimental group (2000 mg/kg b.w. EEM), both orally administered (gavage) at single doses and monitored for 14 days. To assess the genotoxic, mutagenic and apoptotic potential, 50 male Swiss mice were divided into 5 groups (n = 10): Group I: negative control (saline solution 0.1 ml/10 g b.w.); Group II: positive control (cyclophosphamide 100 mg/kg b.w.) intraperitoneally administered; groups III-V received EEM at 500, 1000 and 2000 mg/kg b.w., respectively. Groups I, III-V received oral administrations (gavage). The results showed that there was no acute lethality or any signs of acute toxicity, indicating that LD50 is greater than 2000 mg/kg b.w. The groups treated with EEM showed no genotoxic or mutagenic activity and did not induce apoptosis in the liver and kidney. Therefore, EEM showed no acute toxicity and at doses of 500, 1000 and 2000 mg/kg b.w. absence of genotoxicity, mutagenicity and no apoptotic events were observed.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity.

Pyriproxyfen does not cause microcephaly or malformations in a preclinical mammalian model.

Pyriproxyfen is used in Brazil to combat epidemics of Dengue Fever, Chikungunya Fever, and Zika virus. This study assessed the effects of pyriproxyfen on reproductive performance, embryo-fetal development, head measurements, and DNA integrity in a preclinical model. Thirty pregnant mice were divided into three groups (n = 10): control (drinking water-0.1 ml/10 g (body weight-b.w., gavage) and treated with pyriproxyfen 0.0002 mg/kg and 0.0021 mg/kg (b.w., gavage) during the gestational period. Analysis of biometric, reproductive performance and embryo-fetal development parameters related to control presented no significant differences, suggesting no maternal or embryo-fetal toxicity. Head measurements showed no differences except an increase in anterior/posterior measurement and glabella/external occipital protuberance. Analysis of DNA integrity showed an increase in micronucleus only at 72 h for the lowest dose group. Thus, we infer that pyriproxyfen is not related to the occurrence of microcephaly, nor does it alter reproductive performance, embryo-fetal development or DNA integrity.

Assessment of acute toxicity and cytotoxicity of fluorescent markers produced by cardanol and glycerol, which are industrial waste, to different biological models.

The amphyphylic triazoanilines recently synthesized 1-(4-(3-aminophenyl)-1H-1,2,3- triazole-1-yl)-3-(3-pentadecylphenoxy)propan-2-ol (1) and 1-(4-(4-aminophenyl)-1H- 1,2,3-triazole-1-yl)-3-(3-pentadecylphenoxy)propan-2-ol (2), synthesized from cardanol and glycerol, have photophysical properties which allow their use in the development of fluorescent biomarkers with applicability in the biodiesel quality control. Based on this, the present research evaluated the toxic effects of both compounds in different biological models through the investigation of survival and mortality percentages as a measure of acute toxicity on Daphnia similis and Oreochromis niloticus, larvicidal assay against Aedes aegypti, and cytotoxic activity on mammary cells. Results demonstrate that these triazoanilines 1 and 2 have shown low acute toxicity to the biological models investigated in this study up to the following concentrations: 4.0 mg L-1 (D. similis), 4.0 mg L-1 (A. aegypti larvae), 1.0 mg L-1 (O. niloticus), and 1.0 mg mL-1 (mammary cells). This fact suggests the potential for safe use of compounds 1 and 2 as fluorescent markers for the monitoring of biodiesel quality, even in the case of environmental exposure. Besides all of that, the reuse of cardanol and glycerol, both industrial wastes, favors the maintenance of environmental health and is in agreement with the assumptions of green chemistry. Graphical abstract ᅟ.

The mixture of cashew nut shell liquid and castor oil results in an efficient larvicide against Aedes aegypti that does not alter embryo-fetal development, reproductive performance or DNA integrity.

Dengue fever, chikungunya fever and Zika virus are epidemics in Brazil that are transmitted by mosquitoes, such as Aedes aegypti or Aedes albopictus. The liquid from shells of cashew nuts is attractive for its important biological and therapeutic activities, which include toxicity to mosquitoes of the genus Aedes. The present study evaluated the effects of a mixture of surfactants from natural cashew nutshell liquid and castor oil (named TaLCC-20) on the mortality of larvae and on the reproductive performance, embryonic and fetal development and genetic stability of Swiss mice. A total of 400 Ae. aegypti larvae (third larval stage) were treated with TaLCC-20 concentrations of 0.05 mg/L, 0.5 mg/L, or 5 mg/L (ppm). Twenty pregnant female mice were also orally administered TaLCC-20 at doses of 5 mg/kg and 50 mg/kg body weight (b.w.), and 10 animals were given only drinking water at 0.1 mL/10 g b.w. (orally). The results of a larvicide test demonstrated that 5 mg/mL TaLCC-20 killed 100% of larvae within three hours, which is comparable to the gold standard indicated by the Ministry of Health. Overall, these results show that TaLCC-20 is an efficient larvicide that does not induce genetic damage. In addition, changes in reproductive performance and embryo-fetal development appear positive, and the formulation is cost effective. Therefore, TaLCC-20 is an important product in the exploration of natural larvicides and can assist in fighting mosquitos as vectors for dengue fever, chikungunya fever and Zika virus, which are emerging/re-emerging and require proper management to ensure minimal harm to the human population. Therefore, TaLCC-20 can be considered a key alternative to commercial products, which are effective yet toxigenic.

The safe use of Doliocarpus dentatus in the gestational period: Absence of changes in maternal reproductive performance, embryo-fetal development and DNA integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Doliocarpus dentatus (Dilleniaceae) is commonly used in Brazil for the treatment of inflammatory process pain and urinary retention. Previous studies of our group have demonstrated the anti-inflammatory and antimycobacterial action of the ethanolic extract of Doliocarpus dentatus (EEDd) as well as the safety of its use. AIM OF THE STUDY: we investigated the effects of EEDd on reproductive performance, fetal development and DNA integrity in pregnant female Swiss mice. MATERIAL AND METHODS: thirty female Swiss mice were divided into three experimental groups (n = 10): control group treated with 1% tween-80 and EEDd1 and EEDd2 groups treated with EEDd at doses of 100 and 1000 mg/kg, respectively. The treatment occurred by oral gavage throughout the gestational period. At the end of pregnancy, parameters related to reproductive performance, embryofoetal development and DNA integrity was evaluated. RESULTS: both doses of the extract tested did not alter the reproductive parameters, did not present significant differences in the embryofetal development when compared to the control group and also did not induce the formation of micronuclei. CONCLUSION: the EEDd do not alter the reproductive parameters, embryofetal development and DNA integrity, ensuring its safe use during pregnancy.