Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation

Abstract

<jats:p> Mercury (Hg) represents a ubiquitous environmental heavy metal that could lead to severe toxic effects in a variety of organs usually at a low level. The present study focused on the liver oxidative stress, one of the most important roles playing in Hg hepatotoxicity, by evaluation of different concentrations of mercuric chloride (HgCl<jats:sub>2</jats:sub>) administration. Moreover, the protective potential of curcumin against Hg hepatotoxic effects was also investigated. Eighty-four rats were randomly divided into six groups for a three-days experiment: control, dimethyl sulfoxide control, HgCl<jats:sub>2</jats:sub> treatment (0.6, 1.2, and 2.4 mg kg<jats:sup>−1</jats:sup> day<jats:sup>−1</jats:sup>), and curcumin pretreatment (100 mg kg<jats:sup>−1</jats:sup> day<jats:sup>−1</jats:sup>) groups. Exposure of HgCl<jats:sub>2</jats:sub> resulted in acute dose-dependent hepatotoxic effects. Administration of 2.4 mg kg<jats:sup>−1</jats:sup> HgCl<jats:sub>2</jats:sub> significantly elevated total Hg, nonprotein sulfhydryl, reactive oxygen species formation, malondialdehyde, apoptosis levels, serum lactate dehydrogenase, and alanine transaminase activities, with an impairment of superoxide dismutase and glutathione peroxidase in the liver. Moreover, HgCl<jats:sub>2</jats:sub> treatment activated nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in further investigation, with a significant upregulation of Nrf2, heme oxygenase-1, and γ-glutamylcysteine synthetase heavy subunit expression, relative to control. Pretreatment with curcumin obviously prevented HgCl<jats:sub>2</jats:sub>-induced liver oxidative stress, which may be due to its free radical scavenging or Nrf2-ARE pathway-inducing properties. Taking together these data suggest that curcumin counteracts HgCl<jats:sub>2</jats:sub> hepatotoxicity through antagonizing liver oxidative stress. </jats:p>

Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective

“…Several reports have also recognized the protective capacity of curcumin on liver injury produced by some xenobiotics. Curcumin (100 or 200 mg/kg/day intra peritoneal) has been previously described to exhibit a significant hepatoprotective activity against liver damages induced by aflatoxin B1 [ 96 ], lambda cyhalothrin [ 97 ], CCl 4 [ 98 , 99 ], mercury [ 100 ] and other heavy metals [ 101 ] in adult rats. Levels of lipid peroxidation, serum biomarker enzymes, liver MDA, hydroxyproline and liver antioxidants (i.e., GSH, SOD, catalase) were correspondingly modified after curcumin treatment.…”

“…Regarding protective ability of curcumin against heavy-metals (such as copper, cadmium, chromium, mercury, lead and arsenic), its free radical scavenging/reducing power/chelating capacities can restrain the heavy-metals-promoted hepatotoxicity by liver oxidative stress-related antagonism. These abilities were connected with the induction of the Nrf2/antioxidant response elements/Kelch-like ECH associated protein 1 (Nrf2/ARE/Keap1) pathway [ 100 , 101 ]. On the other hand, curcumin also exhibited a dose-dependent protection in CCl 4 -induced liver damage of Jian carp ( Cyprinus carpio var.…”

Radiation-Mediated Tumor Growth Inhibition Is Significantly Enhanced with Redox-Active Compounds That Cycle with Ascorbate

“…A study on kidney ischemia/reperfusion model showed that Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin contributed to the upregulation of numerous endogenous antioxidant defenses that are, at least in part, controlled by Nrf2 (14). Such scenario was reportedly operative with redox-active curcumin, nitroxides, and flavonoids (22,26,31,39,44,63).…”

Unifying Mechanism Involving Physiological Activity of Spices: Electron Transfer, Reactive Oxygen Species, Oxidative Stress, Antioxidants, Redox Chemistry, and Foods

“…There is a protective effect conferred by the AO in Cd-induced OS and cardiovascular dysfunction 26 . A beneficial influence occurred with curcumin against Hg-induced OS in the liver 27 . The effect is attributed to free radical scavenging.…”