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.

4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy.

Diaryl sulfide analogs of combretastatin A-4: Toxicogenetic, immunomodulatory and apoptotic evaluations and prospects for use as a new chemotherapeutic drug.

Combretastatin A-4 exhibits efficient anti-cancer potential in human tumors, including multidrug-resistant tumors. We evaluated the mutagenic, apoptotic and immunomodulatory potential of two diaryl sulfide analogs of combretastatin A-4, 1,2,3-trimethoxy-5-([4-methoxy-3-nitrophenyl]thio)benzene (analog 1) and 1,2,3-trimethoxy-5-([3-amino-4-methoxyphenyl]thio)benzene (analog 2), as well as their association with the anti-tumor agent cyclophosphamide, in Swiss mice. Such evaluation was achieved using the comet assay, peripheral blood micronucleus test, splenic phagocytosis assay, and apoptosis assay. Both analogs were found to be genotoxic, mutagenic and to induce apoptosis. They also increased splenic phagocytosis, although this increase was more pronounced for analog 2. When combined with cyclophosphamide, analog 1 enhanced the mutagenic and apoptotic effects of this anti-tumor agent. In contrast, analog 2 did not enhance the effects of cyclophosphamide and prevented apoptosis at lower doses. These data suggest that analog 1 could be an adjuvant chemotherapeutic agent and possibly improve the anti-neoplastic effect of cyclophosphamide. Additionally, this compound could be a candidate chemotherapeutic agent and/or an adjuvant for use in combined anti-cancer therapy.