Modulation of early stress-related biomarkers in cytoplasm by the antioxidants silymarin and quercetin using a cellular model of arsenic acute poisoning

SORIA, ELIO A; EYNARD, ALDO R; BONGIOVANNI, GUILLERMINA A.

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 107 p. 982 - 987

1742-7835

Several pathologies (i.e. cancer, diabetes) are increased in arsenic (As)-exposed populations, with oxidative stress being the major toxicological mechanism. Since the flavonoids silymarin (S) and quercetin (Q) afford antioxidant activity on such mechanism, but it is still unknown if this effect is enough to protect cells. In this line, it would be valuable to develop in a model which allow the antioxidant xenobiotic potential against arsenic cytotoxicity to be assessed in an efficient and rapid way. Thus, it was assayed in CHO-K1 cells treated with As, S and Q the oxidant production (e.g. ROS and RNS) and molecular parameters of biological response (e.g. plasma membrane composition, actin microfilaments and activated JNK -diphosphorilated c-Jun N-terminal kinase-) and cellular viability. As caused loss of the cellular viability in a time-dependent manner. This effect was preceded by lipid hydroperoxide (LHP) formation, but not by RNS induction or ganglioside content changes, with both flavonoids counteracting these effects. Despite all treatments had unspecific hormetic responses on nitrite cell release, there was no relation between them and the cellular viability. As induced cytoplasmic MF rearrangement (tight perinuclear distribution with projections, stress fibres and pseudopodia), which was reversed by S. Also, activated JNK showed a similar distribution to actin. Contrarily, Q caused a dysmorphic granular pattern, thus behaving as a toxic agent. Summing up, toxic levels of arsenic disturb the redox homeostasis with LHP induction and early triggering of stress responses in cytoskeleton and cell signalling. Using the proposed model, S showed to protect cells from arsenical cytotoxicity without own toxic properties like Q. Thus, S might be considered for modulation of the human As susceptibility.