Soluble curcumin prevents cadmium cytotoxicity in primary rat astrocytes by improving a lack of GFAP and glucose-6-phosphate-dehydrogenase

Abstract

Cadmium (Cd) is a heavy metal which is widespread in various environmental components. Moreover several occupational diseases have the complications that are related to Cd cytotoxicity. Low doses of Cd exposure could induce pathogenetic disturbances in several sensitive cells as result of its long biological half-life and accumulation in vital tissue types. Prolonged Cd exposure was determined as main factor in accumulation of this metal ion over time in the liver, kidneys and neural tissue cells. The neurotoxic effect of Cd was presented in several articles which reported both in vivo and in vitro study. One of the main causes of Cd neurotoxicity is the ability of this ion to increase the permeability of the blood brain barrier. Despite a focus of attention on Cd cytotoxicity over the last few decades, the effect of Cd in neural tissue cells has been presented in a limited number of articles. The neurotoxic effect of Cd is accompanied by biochemical changes as well as a lack of functional activity of the central nervous system. Taking into account that the cytotoxic effect of Cd is associated with oxidative stress, inflammation and selective cell death, antioxidants could be used to protect neural tissue cells against both chronic and acute Cd exposure. Antioxidants protect diverse cell types against metal induced cytotoxicity. Curcumin is a natural polyphenol which exhibits antioxidant and anti-inflammatory effect. Soluble forms of cucrcumin can penetrate the blood brain barrier and protect neural tissue cells against detrimental effects of cytotoxic compounds. Glial cells are the most numerous cell population in CNS. Astrocytes possess the ability to protect the neuronal cells against cytotoxicity and maintain CNS functions. The cytoskeleton of astrocytes is constructed with glial fibrillary acidic protein (GFAP). GFAP is involved in essential functions of astrocytes and reflects astrocyte reactivity. The molecular mechanisms of the neurotoxic effect of Cd on glial cytoskeleton remain unknown. Primary astrocyte cell culture was used as model to assess the gliotoxic effect of Cd as well as the potency of low doses of soluble curcumin to ameliorate the neurotoxic effect of Cd. The obtained results demonstrated depletion of GFAP and glucose-6-phosphate-dehydrogenase (G6PD) in astrocytes treated with 10 µM Cd. The exposure to 5 µM curcumin ameliorated the expression both of GFAP and G6PD in Cd suppressed astrocytes. Moreover, low doses of soluble curcumin significantly prevented the detrimental effects of Cd on cell viability and indices of oxidative stress. The obtained results are evidence that soluble forms of curcumin improve astrocyte viability, cytoskeleton depletion and glucose utilization pathway. Thus, soluble curcumin possesses a neuroprotective effect directed on astrocyte cytoskeleton and metabolic energy production.

Cadmium-Induced Oxidative Stress: Focus on the Central Nervous System

“…This molecular pathway was also supported by Phuagkhaopong and colleagues in in vitro results demonstrating the release of proinflammatory cytokines mediated by the NF-κB pathway from cultured human astrocyte that underwent to Cd accumulation at non-toxic concentration [150]. Moreover, Cd role in oxidative stress induction was confirmed by the effectiveness of curcumin, a new emerging antioxidant compound, in reverting the increase in Cd-dependent ROS production, lipid peroxidation, and NF-κB activation [151]. It is worth noticing that Ndzvetsky and colleagues observed a decrease in glucose-6-phosphate dehydrogenase (G6PD) expression, speculating that Cd can inhibit primary astrocyte viability through glycolysis disturbance, since G6PD plays a crucial role in metabolic energy, mitochondrial activity and is required for antioxidant defense [152].…”

Influence of cadmium contamination on brain glial cells: consequences and bioindication possibilities

“…Незважаючи на численні дослідження, механізми нейротоксичності Cd залишаються невідомими [31]. Останні дані показали, що токсичний ефект Cd може бути спрямований переважно на функції гліальних клітин [32,36]. Гліальні клітини представлені в мозку хребетних трьома основними типами, зокрема -мікроглія, астроцити та олігодендроцити.…”

“…Цитоскелет еукаріотичних клітин бере участь у ряді життєво важливих процесів, особливо у клітинній реакції на вплив цитотоксичних іонів металів [36]. Крім того, цитоскелет -це динамічна структура, яка забезпечує як форму клітини, так і внутрішньоклітинні регуляторні шляхи [15,26].…”

“…Однією з важливих мішеней цитотоксичності Cd розглядаються цитоскелетні білки та фактори, що контролюють динамічні перебудови цитоскелету [36]. Цитоскелет еукаріотичних клітин бере участь у ряді життєво важливих процесів, особливо у клітинній реакції на вплив цитотоксичних іонів металів [47].…”

Local industrial pollution induces astrocyte cytoskeleton rearrangement in the dice snake brain: GFAP as a biomarker

“…The cytoskeleton proteins, reparative protein A (RPA70), transcriptional regulator nuclear factor kappa-B cells (NF-kB) and DNA damage repairing poly-(ADP-ribose)-polymerase (PARP) were reported as valid biomarkers to estimate aluminium, cadmium, mercury and copper neurotoxicity (Novitsky et al, 2013;Nedzvetsky et al, 2018;Kirici et al, 2019). The study of the effect environmental toxicity on the brain is one of the relevant and major areas of research (Legradi et al, 2018;Pereira et al, 2019;Taysi et al, 2019).…”