Developmental and Reproductive Toxicology of Pesticides

Iyer, Poorni; Makris, Susan L.

doi:10.1016/b978-0-12-374367-1.00012-4

Cited by 16 publications

(10 citation statements)

References 260 publications

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“…Conversely, the effects of the four benzimidazoles on PC cell viability did not appear to correlate with the lipophilicity of the anthelmintic drugs. Despite the different activities of the compounds, all of these drugs affected PC viability with IC 50 values in the range achieved by standard therapeutic dosages [17,[25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…19) µM in Capan-2 ( Figure 1B,C). These IC 50 values were all in the range or even lower than the therapeutic plasma concentrations reached after administration of standard dosages [17,[25][26][27][28]. Notably, parbendazole showed the lowest IC 50 values as compared to other benzimidazoles tested in both cell lines ( Figure 1C), suggesting that the specific substituent at the C5 might be relevant for anti-proliferative activities.…”

Section: Parbendazole Has the Lowest Ic 50 In The Panel Of Tested Benmentioning

confidence: 96%

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The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

Florio

Veschi

Giacomo

et al. 2019

Cancers

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Pancreatic cancer (PC) is one of the most lethal, chemoresistant malignancies and it is of paramount importance to find more effective therapeutic agents. Repurposing of non-anticancer drugs may expand the repertoire of effective molecules. Studies on repurposing of benzimidazole-based anthelmintics in PC and on their interaction with agents approved for PC therapy are lacking. We analyzed the effects of four Food and Drug Administration (FDA)-approved benzimidazoles on AsPC-1 and Capan-2 pancreatic cancer cell line viability. Notably, parbendazole was the most potent benzimidazole affecting PC cell viability, with half maximal inhibitory concentration (IC50) values in the nanomolar range. The drug markedly inhibited proliferation, clonogenicity and migration of PC cell lines through mechanisms involving alteration of microtubule organization and formation of irregular mitotic spindles. Moreover, parbendazole interfered with cell cycle progression promoting G2/M arrest, followed by the emergence of enlarged, polyploid cells. These abnormalities, suggesting a mitotic catastrophe, culminated in PC cell apoptosis, are also associated with DNA damage in PC cell lines. Remarkably, combinations of parbendazole with gemcitabine, a drug employed as first-line treatment in PC, synergistically decreased PC cell viability. In conclusion, this is the first study providing evidence that parbendazole as a single agent, or in combination with gemcitabine, is a repurposing candidate in the currently dismal PC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Parbendazole Has the Lowest Ic 50 In The Panel Of Tested Benmentioning

confidence: 96%

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

Florio

Veschi

Giacomo

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…Studies have shown potential adverse effects of conazoles on cytochrome P450-mediated process in non-target species. For example, propiconazole has been found to interfere with the production of estrogen ( Iyer & Makris, 2010 ) and embryonic development in the crustacean Daphnia magna ( Kast-Hutcheson, Rider & LeBlanc, 2001 ). Long term exposure (≥ 20 days) to propiconazole (≥ 50 µg L −1 ) has also been shown to cause oxidative stress in liver, gill and muscle tissues of rainbow trout Oncorhynchus mykiss ( Li et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Toxicity thresholds of three insecticides and two fungicides to larvae of the coralAcropora tenuis

Flores

Kaserzon

Elisei

et al. 2020

PeerJ

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Tropical marine ecosystems, such as coral reefs, face several threats to their health and resilience, including poor water quality. Previous studies on the risks posed by pesticides have focused on five priority herbicides; however, as the number of pesticides applied in coastal agriculture increases, a suite of ‘alternative’ pesticides is being detected in tropical nearshore waters. To improve our understanding of the risks posed by alternative pesticides to tropical marine organisms, the effects of three insecticides (diazinon, fipronil, imidacloprid) and two fungicides (chlorothalonil, propiconazole) were tested on larval metamorphosis of the coral Acropora tenuis. A. tenuis larvae were affected by all five pesticides and the reference toxicant copper. The no effect concentration (NEC) and the 10% and 50% effect concentrations (EC10 and EC50, respectively) for larval metamorphosis were estimated from concentration-response curves after 48 h exposure. The NEC, EC10 and EC50 (in µg L−1), respectively, of each pesticide were as follows: chlorothalonil (2.4, 2.8, 6.0); fipronil (12.3, 13.9, 29.1); diazinon (38.0, 40.8, 54.7); imidacloprid (263, 273, 347); and propiconazole (269, 330, 1008). These toxicity thresholds are higher than reported concentrations in monitoring programs; however, these data will contribute to improving water quality guideline values, which inform the total risk assessments posed by complex contaminant mixtures to which these pesticides contribute.

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“…Studies have shown potential adverse effects of conazoles on CYP-mediated process in non-target species. For example, propiconazole has been found to interfere with the production of estrogen (Iyer & Makris 2010) and embryonic development in the crustacean Daphnia magna (Kast-Hutcheson et al 2001). Long term exposure (≥ 20 d) to propiconazole (≥ 50 µg L -1 ) has also been shown to cause oxidative stress in liver, gill and muscle tissues of rainbow trout Oncorhynchus mykiss (Li et al 2010).…”

Section: Propiconazolementioning

confidence: 99%

Peer Review #1 of "Toxicity thresholds of three insecticides and two fungicides to larvae of the coral Acropora tenuis (v0.1)"

Reichelt‐Brushett¹

2020

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Developmental and Reproductive Toxicology of Pesticides

Cited by 16 publications

References 260 publications

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

Toxicity thresholds of three insecticides and two fungicides to larvae of the coralAcropora tenuis

Peer Review #1 of "Toxicity thresholds of three insecticides and two fungicides to larvae of the coral Acropora tenuis (v0.1)"

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