Milk thistle seed extract protects rat C6 astroglial cells from acute cocaine toxicity

Abstract

Cocaine is a powerful addictive drug, widely abused in most Western countries. It easily reaches various domains within and outside of the central nervous system (CNS), and triggers varying levels of cellular toxicity. No pharmacological treatment is available to alleviate cocaine-induced toxicity in the cells without side-effects. Here, we discerned the role of milk thistle (MT) seed extract against cocaine toxicity. First, we investigated acute cytotoxicity induced by treatment with 2, 3 and 4 mM cocaine for 1 h in astroglial, liver and kidney cells in vitro, and then in living shrimp larvae in vivo. We showed that astroglial cells are more sensitive to cocaine than liver, kidney cells or larvae. Cocaine exposure disrupted the general architecture of astroglial cells, induced vacuolation, decreased cell viability, and depleted the glutathione (GSH) level. These changes may represent the underlying pathology of cocaine in the astrocytes. By contrast, MT pretreatment (200 μg/ml) for 30 min sustained the cell morphological features and increased both cell viability and the GSH level. Besides its protective effects, the MT extract was revealed to be non-toxic to astroglial cells, and displayed high free-radical scavenging activity. The results from this study suggest that enhanced GSH level underlies cell protection, and indicate that compounds that promote GSH synthesis in the cells may be beneficial against cocaine toxicity.

N-Acetyl Cysteine Mitigates the Acute Effects of Cocaine-Induced Toxicity in Astroglia-Like Cells

“…Our data provide compelling evidence to support the hypothesis that inhibition of the early response changes by NAC enhances cell survival through increased GSH levels. Compounds which support GSH synthesis could therefore mitigate toxicity of early response events in cells exposed to cocaine [ 22 ]. The recapitulation of cocaine-induced changes observed in our model (e.g.…”

“…Taken together, these properties demonstrate that C6 cell cultures behave like an astroglia-like cell line. In the past, C6 cells have also been used extensively for in vitro drug abuse research [ 7 , 8 , 19 – 22 ] and in the study of astrocytic function [ 23 – 30 ].…”

The Drosophila brain on cocaine at single-cell resolution

“…Glutamatergic neurons feature prominently in C1, C3, C21, and C33. Studies on rats have shown that cocaine is toxic to astrocytes and that loss of astrocytes leads to dysfunctional neuron-glia communication (Badisa et al 2013(Badisa et al , 2014(Badisa et al , 2015. Eaat1, which is highly expressed in astrocytes (Supplemental Table S4), encodes a transmembrane glutamate transporter involved in glia-neuron communication (MacNamee et al 2016).…”