Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies
- PMID: 26170741
- PMCID: PMC4499649
- DOI: 10.4196/kjpp.2015.19.4.365
Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies
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.
Keywords: Acute toxicity; Aripiprazole; Cocrystal; Immunotoxicology; Survival proteins.
Figures
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References
-
- Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174:1930–1933. - PubMed
-
- Takaki M, Ujike H. Aripiprazole is effective for treatment of delayed sleep phase syndrome. Clin Neuropharmacol. 2014;37:123–124. - PubMed
-
- De Berardis D, Fornaro M, Serroni N, Marini S, Piersanti M, Cavuto M, Valchera A, Mazza M, Girinelli G, Iasevoli F, Perna G, Martinotti G, Di Giannantonio M. Treatment of antipsychotic-induced hyperprolactinemia: an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole. Recent Pat Endocr Metab Immune Drug Discov. 2014;8:30–37. - PubMed
-
- Arunagiri P, Rajeshwaran K, Shanthakumar J, Tamilselvan T, Balamurugan E. Combination of omega-3 Fatty acids, lithium, and aripiprazole reduces oxidative stress in brain of mice with mania. Biol Trace Elem Res. 2014;160:409–417. - PubMed
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