Toxicology Reports
Toxicology Reports
Toxicology Reports
Toxicology Reports
journal homepage: www.elsevier.com/locate/toxrep
a r t i c l e i n f o a b s t r a c t
Article history: The 1,4-naphthoquinones, important members of the family of quinones are used as both crude extracts
Received 4 July 2016 and as compound manipulated by the pharmaceutical industry. They have gained great emphasis by pre-
Received in revised form 29 August 2016 senting different pharmacological properties as antibacterial, antiviral, antiprotozoal and anthelmintic,
Accepted 15 September 2016
and has antitumor activity. Our aim was to evaluate the cytotoxicity, hemolytic activity and in vivo acute
Available online 16 September 2016
toxicity of three derivatives of 2-hydroxy-1,4-naphthoquinones. The cell viability in vitro against RAW
Cell Line displayed IC50 ranging of 483.52044.8 M, whereas in primary culture tests using murine
Keywords:
macrophages, IC50 were 315.81408.0 M for naphthoquinones derivatives 4a and 4c respectively,
Naphthoquinones
Cytotoxicity
besides no hemolysis was observed at the dose tested. The in vivo acute toxicity assays exhibited a
Hemolytic activity signicant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg, and
Acute toxicity at a dose of 1000 mg/kg the derivatives not triggering signs of toxicity although the compound 4a have
promoted hepatic steatosis and hyperemia in kidney tissue. Thereby, these modications decrease the
toxicity of the tested derivatives naphthoquinones, providing a high potential for the development of
news drugs.
2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
http://dx.doi.org/10.1016/j.toxrep.2016.09.007
2214-7500/ 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
V.S. de Sena Pereira et al. / Toxicology Reports 3 (2016) 756762 757
Table 1
Antimalarial activity of three novel naphthoquinoidal derivatives measured by reduction of parasitaemia by Plasmodium berghei and survival of mice treated as compared to
untreated mice control.
Table 2
IC50 (M) of RAW 264.7 cells and murine resident peritoneal macrophages (RPM) exposured to concentration serial dilution of naphthoquinones derivatives.
Results show the mean of IC50 values SD (concentration required to inhibit cell growth by 50%) in micromolar. Data represent the means of three independent experiments,
with each concentration tested in triplicate.
a
Resident peritoneal macrophages.
Table 3
Signs of acute toxicity and mortality derivatives naphthoquinones 4a, 4c and 4d.
Fig. 6. Analysis representative histological sections of the livers of mice treated with derivatives naphthoquinones orally administered (dose 1.000 mg/kg) and untreated
control. The arrowheads indicate inammatory inltrates. Asterisks indicate congested vessels. The square indicates steatosis. (Hematoxylin & Eosin, magnication 400).
Fig. 7. Histological sections stained, with periodic acidschiff (PAS) method, of the livers of mice treated with derivatives naphthoquinones orally administered (dose
1.000 mg/kg) and untreated control. In the image, the circles stand one hepatocyte. Black arrows point the nucleus of hepatocytes and large arrows show the glycogen. While
accumulation of lipids doesnt show a positive reaction the method; hashtags (4a) show the lipid droplets indicating steatosis. The asterisk shows a congested vessel and the
arrow head indicates inammatory inltrate.
cal changes in liver of mice treated, being observed only points of Second Munday et al. [28], beyond the hemolytic activity,
inammatory inltrate and congested vessels. Derivative 4a was many naphthoquinone derivatives can cause necrosis of tubular
the one who presents steatosis, proving to be more hepatotoxic epithelial cells, the substituents at C-3 of position 3 of the 2-
than the other compounds. hydroxy and 2-amino-1,4-naphthoquinone reduces or eliminates
V.S. de Sena Pereira et al. / Toxicology Reports 3 (2016) 756762 761
Fig. 8. Histological analysis of representative sections of the kidney of mice treated with derivatives naphthoquinones orally administered (dose 1.000 mg/kg) and untreated
control. The arrowheads indicate bleeding tissue (Hematoxylin & Eosin, magnication 400).
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