Effect of the dibenzylbutyrolactone lignan (−)-hinokinin on doxorubicin and methyl methanesulfonate clastogenicity in V79 Chinese hamster lung fibroblasts

Resende, Flávia Aparecida; Tomazella, Iara Maluf; Barbosa, Lorrana Vietro; Ponce, Marina; Furtado, Ricardo Andrade; Pereira, Ana Carolina; Bastos, Jairo Kenupp; Silva, Márcio Luís Andrade e; Tavares, Denise Crispim

doi:10.1016/j.mrgentox.2010.04.023

Cited by 25 publications

(29 citation statements)

References 33 publications

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“…The results obtained with the three doses of DNK administered to mice did not evidence any significant correlation between dose and response, probably because the pharmacokinetic parameters can be involved with the lack of correlation between dose and response. In addition, Resende et al (2010) did not find any dose-response correlation when they conducted the micronuclei test for (-)-hinokinin, a semi-synthetic compound derived from (-)-cubebin. Therefore, pharmacokinetic studies, measuring drug concentrations in the body and the target organs, might aid in the evaluation of DNK in vivo.…”

Section: Discussionmentioning

confidence: 93%

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

et al. 2015

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The chemotherapy of schistosomiasis relies on the use of praziquantel. However, concerns over drug resistance have encouraged the search for new drug leads. This paper is the first report on the in vitro and in vivo activity of (-)-6,6'-dinitrohinokinin (DNK) against Schistosoma mansoni. In vitro, the lethal concentrations for 50% of parasites (LC50) of DNK against adult worms were 103.9±3.6 and 102.5±4.8μM at 24 and 72h, respectively. Scanning electron microscopy images showed extensive tegumental alterations such as peeling and smaller numbers of tubercles in the spine of adult worms. DNK also elicited high mortality of schistosomula, with LC50 values of 57.4±2.3, 32.5±0.9, and 20.4±1.2μM at 24, 48, and 72h, respectively. DNK displayed moderate activity against the juvenile liver parasite, with an LC50 value of 179.5±2.3 μM at 72h. This compound reduced the total number of eggs by over 83%, and it affected the development of eggs produced by adult worms. The selectivity index showed that at 24h, DNK was 8.5 and 15.4 times more toxic to the adult worms and schistosomula than to Chinese hamster lung fibroblast cells, respectively. Treatment of infected mice with DNK moderately decreased worm burden (33.8-52.3%), egg production (40.7-60.0%), and spleen and liver weights. Together, our results indicated that DNK presents moderate in vitro and in vivo activities against S. mansoni, and it might therefore be interesting to explore the structure-activity relationship of the antischistosomal activity of this compound.

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Section: Discussionmentioning

confidence: 93%

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

et al. 2015

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“…, 1973; Blum and Carter, 1979; Young et al , 1981; Resende et al , 2010). In addition to producing highly toxic free radicals, doxorubicin cause random breaks in DNA through the inhibition of topoisomerase II and helicase activity, interfering in the separation of double-stranded DNA (Kitada et al , 1994; Coquelle et al , 1997; Quiles et al , 2002; Islaih et al , 2005).…”

Section: Introductionmentioning

confidence: 99%

Identifying Mazama gouazoubira (Artiodactyla; Cervidae) chromosomes involved in rearrangements induced by doxorubicin

2017

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The process of karyotype evolution in Cervidae from a common ancestor (2n = 70, FN = 70) has been marked by complex chromosomal rearrangements. This ancestral karyotype has been retained by the current species Mazama gouazoubira (Fischer 1814), for which a chromosomal polymorphism (Robertsonian translocations and the presence of B chromosomes) has been described, presumably caused by a chromosome fragility. Thus, this study has identified doxorubicin-induced chromosome aberrations and mapped the regions involved in breaks, which may be related to the chromosome evolution process. G-banding pattern showed that 21 pairs of chromosomes presented chromosomal aberrations, 60% of the total chromosome number of the species M. gouazoubira. Among chromosomes that carry aberrations, the region where they were most frequently concentrated was distal relative to the centromere. These data suggest that certain chromosomal regions may be more susceptible to chromosome fragility and consequently could be involved in karyotype differentiation in species of the family Cervidae.

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“…38) According to the literature, the protective activity of plant extracts can also be attributed to the presence of lignans, which are able to scavenge free radicals, protecting and stabilizing the genome. 39) Resende et al 40) evaluated the genotoxic and chemopreventive activity of (−)-hinokinin, a substance derived from dibenzylbutyrolactone lignan (−)-cubebin, in V79 cells. These authors postulated the antioxidant activity as a chemopreventive mechanism presented by (−)-hinokinin.…”

Section: Discussionmentioning

confidence: 99%

“…VP-16 is an anticancer agent that inhibits topoisomerase II. 21) Experimental Design For the assessment of genotoxicity by the comet and micronucleus assays, the concentrations of SCHE (5,10,20,40, 60 µg/mL) were chosen based on the results obtained in the clonogenic efficiency assay using cytotoxicity as a criterion. The concentrations of EG and HE were selected based on the amount of these chemical markers in SCHE, which account for 0.66 and 0.043%, respectively.…”

Section: )mentioning

confidence: 99%

Influence of <i>Styrax camporum</i> and of Chemical Markers (Egonol and Homoegonol) on DNA Damage Induced by Mutagens with Different Mechanisms of Action

Oliveira

Damasceno

Nicolella

et al. 2016

Biological & Pharmaceutical Bulletin

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Effect of the dibenzylbutyrolactone lignan (−)-hinokinin on doxorubicin and methyl methanesulfonate clastogenicity in V79 Chinese hamster lung fibroblasts

Cited by 25 publications

References 33 publications

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

In vitro and in vivo anthelmintic activity of (−)-6,6′-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni

Identifying Mazama gouazoubira (Artiodactyla; Cervidae) chromosomes involved in rearrangements induced by doxorubicin

Influence of <i>Styrax camporum</i> and of Chemical Markers (Egonol and Homoegonol) on DNA Damage Induced by Mutagens with Different Mechanisms of Action

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