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Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies.

Baek KS, Ahn S, Lee J, Kim JH, Kim HG, Kim E, Kim JH, Sung NY, Yang S, Kim MS, Hong S, Kim JH, Cho JY - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: In contrast, the patterns of these phospho-proteins were variable in other tissues.Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages.Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea.

ABSTRACT
Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor (NF)-κB, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

No MeSH data available.


Related in: MedlinePlus

Acute toxicity of ARPGCB or GCB3004 in mice. (A) The levels of serum parameters (AST and ALT) from mice orally administered ARPGCB or GCB3004 (each 500 mg/kg). (B) Organs from mice orally administered with ARPGCB or GCB3004 (each 500 mg/kg). Data represent the mean±SD of an experiment performed with five mice.
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Figure 1: Acute toxicity of ARPGCB or GCB3004 in mice. (A) The levels of serum parameters (AST and ALT) from mice orally administered ARPGCB or GCB3004 (each 500 mg/kg). (B) Organs from mice orally administered with ARPGCB or GCB3004 (each 500 mg/kg). Data represent the mean±SD of an experiment performed with five mice.

Mentions: All data in this paper are presented as the mean±SD experiments performed with five (Fig. 1) or six (Fig. 3 and 4) samples. For statistical comparisons, these results were analyzed using ANOVA/Scheffe's post hoc test and Kruskal-Wallis/Mann-Whitney test. p-values<0.05 were considered statistically significant. All statistical tests were carried out using the computer program SPSS (SPSS Inc., Chicago, IL, USA). Similar experimental data were also observed by an additional independent set of in vitro and in vivo experiments performed with the same numbers of samples or mice.


Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies.

Baek KS, Ahn S, Lee J, Kim JH, Kim HG, Kim E, Kim JH, Sung NY, Yang S, Kim MS, Hong S, Kim JH, Cho JY - Korean J. Physiol. Pharmacol. (2015)

Acute toxicity of ARPGCB or GCB3004 in mice. (A) The levels of serum parameters (AST and ALT) from mice orally administered ARPGCB or GCB3004 (each 500 mg/kg). (B) Organs from mice orally administered with ARPGCB or GCB3004 (each 500 mg/kg). Data represent the mean±SD of an experiment performed with five mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499649&req=5

Figure 1: Acute toxicity of ARPGCB or GCB3004 in mice. (A) The levels of serum parameters (AST and ALT) from mice orally administered ARPGCB or GCB3004 (each 500 mg/kg). (B) Organs from mice orally administered with ARPGCB or GCB3004 (each 500 mg/kg). Data represent the mean±SD of an experiment performed with five mice.
Mentions: All data in this paper are presented as the mean±SD experiments performed with five (Fig. 1) or six (Fig. 3 and 4) samples. For statistical comparisons, these results were analyzed using ANOVA/Scheffe's post hoc test and Kruskal-Wallis/Mann-Whitney test. p-values<0.05 were considered statistically significant. All statistical tests were carried out using the computer program SPSS (SPSS Inc., Chicago, IL, USA). Similar experimental data were also observed by an additional independent set of in vitro and in vivo experiments performed with the same numbers of samples or mice.

Bottom Line: In contrast, the patterns of these phospho-proteins were variable in other tissues.Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages.Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea.

ABSTRACT
Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor (NF)-κB, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

No MeSH data available.


Related in: MedlinePlus