Cocaine potentiates an inflammatory response in C6 astroglia‑like cells

Agharahimi,Maryam; Badisa,Ramesh B.; Mazzio,Elizabeth; Soliman,Karam F.; Goodman,Carl B.

doi:10.3892/br.2021.1421

Cocaine potentiates an inflammatory response in C6 astroglia‑like cells

Authors:
- Maryam Agharahimi
- Ramesh B. Badisa
- Elizabeth Mazzio
- Karam F. Soliman
- Carl B. Goodman
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Affiliations: College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA
Published online on: March 16, 2021 https://doi.org/10.3892/br.2021.1421
Article Number: 45
Copyright: © Agharahimi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cocaine is a highly addictive drug that mediates its effect through altering dopamine metabolism in the central nervous system (CNS), resulting in a feeling of euphoria. Owing to its high lipophilicity, cocaine easily crosses the blood brain barrier of the CNS and reaches various domains of the brain, where it can trigger cellular damage. Cocaine‑induced CNS damage may arise due to increased levels of free radicals and nitric oxide (NO) in immunecompetent astroglial cells. In the present study, the potential ability of cocaine to exacerbate the production of inflammatory products, primarily superoxide free radicals (O₂‑), hydrogen peroxide (H₂O₂) and NO/nitrite (NO₂‑) was examined in rat C6 astroglia‑like cells challenged with lipopolysaccharide (LPS), a bacterial endotoxin, and interferon gamma (IFNγ), a pro‑inflammatory cytokine. Furthermore, the role of cocaine in increasing the expression of hypoxia inducible factor‑1 (HIF‑1α) and vascular endothelial growth factor (VEGF) in cells was also determined. First, the viability of the cells was assessed when treated with cocaine (0.5‑7 mM) for 24 and 48 h. The results showed that cocaine toxicity was both time and dose‑dependent. In subsequent studies, cells were challenged with or without LPS and IFNγ, followed by co‑treatment with cocaine (1‑4 mM) for 24 h. Cocaine treatment did not increase O₂‑ or H₂O₂ production in the challenged or unchallenged cells. Similarly, cocaine treatment did not increase NO/NO₂‑ production in the unchallenged cells; however, NO/NO₂‑ levels in the challenged cells was increased 40‑50‑fold upon cocaine treatment compared with the corresponding unchallenged group. The HIF‑1α and VEGF levels were significantly increased in the challenged cells at higher cocaine doses compared with the unchallenged cells. Since high concentrations of NO are associated with inflammation, the high levels of NO production observed in the present study suggested that cocaine may have potentiated the inflammatory response in the challenged C6 astroglia‑like cells.

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