Aluminum Trichloride Induces Hypertension and Disturbs the Function of Erythrocyte Membrane in Male Rats

Abstract

Aluminum (Al) is the most abundant metal in the earth's crust. Al accumulates in erythrocyte and causes toxicity on erythrocyte membrane. The dysfunction of erythrocyte membrane is a potential risk to hypertension. The high Al content in plasma was associated with hypertension. To investigate the effect of AlCl3 on blood pressure and the function of erythrocyte membrane, the rats were intragastrically exposed to 0, 64(1/20 LD50), 128(1/10 LD50), and 256(1/5 LD50) mg/kg body weight AlCl3 in double distilled water for 120 days, respectively. Then, we determined the systolic and mean arterial blood pressures of rats, the osmotic fragility, the percentage of membrane proteins, the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-pX), and malondialdehyde (MDA) content of the erythrocyte membrane in this experiment. The results showed that AlCl3 elevated the systolic and mean arterial blood pressure of rats, increased the osmotic fragility, decreased the percentage of membrane protein, inhibited the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, CAT, SOD and GSH-pX, and increased the MDA content of erythrocyte membrane. These results indicate that AlCl3 may induce hypertension by disturbing the function of erythrocyte membrane.

Aluminium toxicosis: a review of toxic actions and effects

“…Oxidative stress, lipid peroxidation Kattab et al, 2010;Exley, 2013;Abd-Elhady et al, 2013;Zhang et al, 2016;Yang et al, 2018;Yu et al, 2019 Pro-inflammatory: organ inflammation in lung, intestine, heart, and testis Fogarty et al, 1998;Verma et al, 2007;Lerner, 2007;Exley, 2013;Taiwo, 2014;de Chambrun et al, 2014;Gherardi et al, 2016;Martinez et al, 2017;Hangouche et al, 2017 Immunosupression: induces lymphocyte apoptosis and dysfunction, inhibits lymphocyte proliferation, causes macrophage dysfunction Nordal and Dahl, 1988;Kammalov et al, 2011;She et al, 2012;Zhu et al, 2014;Zhuang et al, 2016;Xu et al, 2018;Yu et al, 2019 Protein denaturation and transformation Exley et al, 2006;Mujika et al, 2018 Enzymatic stimulation or inhibition Ohsaka and Nomura, 2016 Metabolic impairment: impairs glycolysis and Kreb's cycle; promotes lipid and protein oxidation Xu et al 1990;Mailloux et al, 2006 Genotoxicity: reduced cell proliferation and differentiation, dysneurogenesis Nam et al, 2014 Amyloidogenic and anti-amyloidolytic Sakamoto et al, 2006;Xu et al, 2016 Acts as metalloestrogen, promotes proliferation and migration of breast cancer cells Bakir and Darbre, 2015;Darbre, 2016 Induces teratogenesis causing foetal and neonatal defects Malekshah et al, 2005;Wang et al, 2012;El Mazoudy and Bekhet, 2016 Disrupts mineral metabolism of Fe, P, Ca, Zn, Cu by altering intestinal absorption and cellular uptake…”

“…The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) are affected by Al exposure because of oxidative stress (Oteiza et al, 1993a;Julka and Gill, 1996;Campbell et al, 1999). Abnormal increases in levels of malondealdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) were reported along with decreased levels of antioxidants such as GSH, GPx, SOD, and CAT in tissue homogenates of rats exposed to Al (Anane and Creppy, 2001;Gonzalez et al, 2007;Newairy et al, 2009;Khattab et al, 2010;Bai et al, 2012;Exley, 2013;Abd-Elhady et al, 2013;Zhang et al, 2016;Yu et al, 2019).…”

“…The secretion of the hormone, sometimes increases when Al ion is stimulatory to the gland or because the target organs are refractory or unresponsive to the hormone when there is receptor depletion or decreased expression of the receptor on the cell membrane. The Al ions act as chemical stressor by promoting the release of norepinerphrine (Zhuang et al, 2016) and cortisol (Vasanthan and Joshi, 2018); and the elevated levels of these hormones can cause increase in blood pressure (Zhang et al, 2016). Elevated blood insulin level is associated with insulin resistance due to depletion of glucose transporter-4 protein expression in skeletal muscles during Al exposure (Wei et al, 2018).…”

“…Cell membrane functions which regulate transmembrane transport of ions are expected to be disrupted when ATPase in cell membrane loses some level of activity during Al exposure. There are reports showing that Al inhibited activities of Na + K + -ATPase, Mg 2+ -ATPase and Ca 2+ -ATPase in erythrocytes (Zhang et al, 2016), vascular endothelial cells (Vorbrodt et al, 1994), testes (Sun et al, 2018) and ovaries (Fu et al, 2014) of rats. The Al-induced change in erythrocyte size may also be accompanied by change in erythrocyte shape resulting in the formation of echinocytes (Suwalsky et al, 2004), acanthocytes and stomatocytes (Vittori et al, 2002) in vitro, due to altered membrane morphology (Lukyanenko et al, 2013).…”

A review of the factors that influence erythrocyte osmotic fragility

“…Various concentrations of aqueous solutions of tris acetylacetonate aluminium (III) (Al (acac) 3 , tris maltolate aluminium (III) (Al(malt) 3 and tris aluminium lactate (Al(lac) 3 ) caused erythrocytes to be osmotically fragile (Zatta et al, 1989). Treatment of rat erythrocytes with aluminium chloride caused increased osmotic fragility due to increased lipid peroxidation (Gutteridge et al, 1995;Hernández et al, 2008;Al-Qayim et al, 2014;Oztürk & Ozdemir, 2015;Zhang et al, 2016). However, Bazzoni et al (2005) reported improved stability of erythrocyte membrane and reduced erythrocyte size and aggregation in adult male rats after parenteral treatment with aluminium hydroxide.…”