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. 2020 Sep 4:2020:7915795.
doi: 10.1155/2020/7915795. eCollection 2020.

Herbicide Widespread: The Effects of Pethoxamid on Nonalcoholic Fatty Liver Steatosis In Vitro

Anna Virginia Adriana Pirozzi  1 , Antonietta Stellavato  1 , Chiara Schiraldi  1 , Mariateresa Giuliano  1
Affiliations

Herbicide Widespread: The Effects of Pethoxamid on Nonalcoholic Fatty Liver Steatosis In Vitro

Anna Virginia Adriana Pirozzi et al. J Toxicol. .

Abstract

Pethoxamid is a widespread herbicidal product, presenting itself as an extremely flexible active substance and with a high potential for use as an herbicide for preemergence. The emergence of multiple resistance in crops has been addressed using combinations of preemergence and postemergence herbicides in the same seeding-harvest cycle. A winning combination of pethoxamid and glyphosate mainly affected the acidobacteria population. Glyphosate scientific literature has demonstrated an observational link between herbicide exposure and liver disease in human subjects. Identifying and ranking the risk to the public that pethoxamid could exert on target organs has not been evaluated so far. Due to similarities to glyphosate, we did look at the effect of pethoxamid on impaired liver cells HepG2, using a nonalcoholic fatty liver disease (NAFLD) cell model in vitro. Pethoxamid was cytotoxic starting at 1 ppm. Fatty acid accumulation (FA) was enhanced while low doses of pethoxamid slightly decreased LDH protein expression compared to FA-treated HepG2. The same trend was observed for cytochrome c. Based on our data, we can argue that NAFLD hepatic cells react to pethoxamid trying detoxifying strategies, ready to undergo cell death to avoid further degeneration. Downregulation of cytochrome can lead to the hypothesis that pethoxamid should not induce herbicide resistance.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
(a) Dose-dependent cytotoxicity of pethoxamid. Cell viability was significantly affected starting at 10 ppm in 24 h. Values are means ± SD from three separate experiments. (b) Representative HepG2 pictures panel in the presence of pethoxamid at different concentrations. ∗P < 0.05 and ∗∗P < 0.01t-test analyses were performed to compare the significance of each treatment with respect to CTR.
Figure 2
Figure 2
Oil red staining showed an increased steatosis at low-dose exposure. (a) Oil red O staining pictures for HepG2 cells in presence of fatty acids (FA) 6 mM, and pethoxamid-treated cells at different concentrations (0.1–500 ppm). (b) Spectophotometric quantification of lipid amount percentage with respect to the control of steatotic cells (FA 6 mM). ∗P < 0.05t-test analyses were performed to compare the significance of each treatment with respect to CTR. Values are means ± SD from three separate experiments.
Figure 3
Figure 3
Western blot for LDH and cytochrome c. Densitometry plot (a) showing an inverse dose-dependent reduction of LDH levels in pethoxamid-treated cells. Densitometry plot (b, c) demonstrating LDH and cytochrome c reduction. Actin was used to normalize the results. Values are means ± SD from three separate experiments.
See this image and copyright information in PMC

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