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. 2018 Dec 19;16(4):1559325818816284.
doi: 10.1177/1559325818816284. eCollection 2018 Oct-Dec.

Prophylactic Administration of Nanocurcumin Abates the Incidence of Liver Toxicity Induced by an Overdose of Copper Sulfate: Role of CYP4502E1, NF-κB and Bax Expressions

Ahlam Alhusaini  1 , Iman H Hasan  1 , Nouf Aldowsari  2 , Njood Alsaadan  2
Affiliations

Prophylactic Administration of Nanocurcumin Abates the Incidence of Liver Toxicity Induced by an Overdose of Copper Sulfate: Role of CYP4502E1, NF-κB and Bax Expressions

Ahlam Alhusaini et al. Dose Response. .

Abstract

Background: The consequences of excess copper in human tissue are the alterations in the oxidative stress markers and peroxidative damage of membrane lipids. Unselective copper binding may be the clue to damaging impact to protein construction and hence modifying their biological functions. The aim of this study is to match the hepatoprotective efficacy of curcumin (CM) or nanocurcumin (NCM) with that of desferrioxamine (DSF; standard heavy metal chelator) against toxic doses of copper sulphate (CuSO4).

Method: All treatments were given simultaneously with CuSO4 for 7 days.

Result: CuSO4 administration elevated serum alanine transaminase, and hepatic nitric oxide (NO), lipid peroxide, and caspase-3 as well as protein expression of cytochrome P4502E1, and nuclear factor-κB (NF-κB) and Bax gene expressions. On the other hand, hepatic levels of reduced glutathione, superoxide dismutase, and interleukin-10 were decreased, whereas DNA degradation was increased as well compared with the control group. The administration of the aforementioned antioxidants ameliorated all the previous altered measured parameters. Interestingly, NCM achieved the most pronounced hepatoprotective effect nearly equivalent to that of DSF.

Conclusion: It was concluded that NCM is considered a promising candidate against CuSO4 toxicity, and cytochrome P450, NF-κB, and Bax are involved in its toxicity and treatment.

Keywords: Bax; CYP450; DNA degradation; IL-10; NF-κB; gene expressions; nanocurcumin.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
IL-10 and caspase-3 levels in hepatic tissues in control, CuSO4-intoxicated group, as well as in all treated groups. Data are presented as mean ± SEM (N = 6). *** P ≤ .001 versus control group, and +++ P≤ .001, +++ P ≤ .01, and + P ≤ .05 versus CuSO4-intoxicated group. IL-10 indicates interleukin-10; SEM, standard error of the mean.
Figure 2.
Figure 2.
A, Western blot analysis of the expression of cytochrome-P450 in control, CuSO4-intoxicated, and all treated groups. B, The densitometry analysis of the expression of cytochrome-P450 proteins in control, CuSO4-intoxicated, and all treated groups. (Data corrected by β-actin and expressed as protein/β-actin). Data are presented as mean ± SEM (N = 6). *** P ≤ .001 versus control group, and +++ P ≤ .001 versus CuSO4-intoxicated group. SEM indicates standard error of the mean.
Figure 3.
Figure 3.
Hepatic DNA fragments in control group, CuSO4-intoxicated group, as well as in all treated groups. Data are expressed as means ± SEM of 6 rats. *** P ≤ .001 versus control group, and +++ P ≤ .001, +++ P ≤ .01, and + P ≤ .05 versus CuSO4-intoxicated group. SEM indicates standard error of the mean.
Figure 4.
Figure 4.
mRNA expression of hepatic NF-κB and Bax in control, CuSO4-intoxicated group, and different treated groups. Data are presented as mean ± SEM (N = 6). *** P ≤ .001 versus control group, and +++ P ≤ .001 versus CuSO4-intoxicated group. mRNA indicates messenger RNA; NF-κB, nuclear factor-κB; SEM, standard error of the mean.
See this image and copyright information in PMC

References

    1. Trumbo P, Yates AA, Schlicker S, Poos M. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc. 2001;101(3):294–291. - PubMed
    1. Barceloux DG. Copper. J Toxicol Clin Toxicol. 1999;37(2):217–230. - PubMed
    1. King CH, Bertsch D. Historical perspective: snail control to prevent schistosomiasis. PLoS Negl Trop Dis. 2015;9(4):e0003657. - PMC - PubMed
    1. Musacco-Sebio R, Ferrarotti N, Saporito-Magriñá C, et al. Oxidative damage to rat brain in iron and copper overloads. Metallomics. 2014;6(8):1410–1416. - PubMed
    1. Zhang SS, Noordin MM, Rahman SO, Haron J. Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats. Vet Hum Toxicol. 2000;42(5):261–264. - PubMed