Low concentrations of sodium arsenite induce hepatotoxicity in prepubertal male rats

Abstract

Arsenic (As) can contaminate air, soil, water, and organisms through mobilization of natural mineralogical deposits or anthropogenic actions. Inorganic‐As compounds are more toxic and widely available in aquatic environments, including drinking water reservoir catchments. Since little is known about its effects on prepubertal mammals, the present study focused on it. Hence, As was administered through drinking water to male Wistar rats from postnatal day 23 to 53. Negative control group received vehicle only (filtered water); As 1 group received AsNaO2 at 0.01 mg L−1 and As2 group received AsNaO2 at 10 mg L−1. It was investigated hepatic and renal toxicity of AsNaO2 (ie, histopathology and apoptosis analysis), as well as its mutagenicity (ie, micronucleus test in liver and bone marrow), cytotoxicity (ie, frequency and type of erythrocytes in blood), and genotoxicity (ie, comet assay in blood). Also, As determination was performed in hepatic and renal tissues. Data obtained revealed that immature organisms present a pattern of arsenic accumulation similar to that observed in adults, suggesting similarity in metabolic processes. In addition, liver showed to be an important target tissue for As toxicity in these experimental conditions, exhibiting infiltrate of defense cells, DNA damages, and increased apoptosis rates.

Nephroprotective effects of chlorogenic acid against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

“…7 Arsenic is methylated in the liver where it binds to liver macromolecules to generate free radicals, which induce oxidative stress and tissue damage. 3 To date, several endogenous free radical scavengers (including enzymatic factors such as catalase, superoxide dismutase (SOD), and selenium and / or non-selenium-dependent glutathione peroxidase (GPx) and nonenzymatic scavengers, such as glutathione (GSH); bilirubin; albumin; vitamins A, E, and C; selenium, uric acid, and coenzyme Q-10, have been identified in both the membranes and cytoplasm of cells. 8 Arsenic induces oxidative pressure through excessive overproduction of reactive oxygen and nitrogen species (ROS/RNS), depletion of the antioxidant capacity of cells, 5 and suppression of DNA repair mechanisms.…”

“…Arsenic toxicity has reportedly caused abnormal ultrastructural changes in the renal tissue of exposed animals 7 . Arsenic is methylated in the liver where it binds to liver macromolecules to generate free radicals, which induce oxidative stress and tissue damage 3 . To date, several endogenous free radical scavengers (including enzymatic factors such as catalase, superoxide dismutase (SOD), and selenium and / or non‐selenium‐dependent glutathione peroxidase (GPx) and nonenzymatic scavengers, such as glutathione (GSH); bilirubin; albumin; vitamins A, E, and C; selenium, uric acid, and coenzyme Q‐10, have been identified in both the membranes and cytoplasm of cells 8 .…”

“…Inorganic As, in both the arsenite and arsenate forms, is more toxic than methylated As 2 . However, both the organic and inorganic forms are present at high concentrations in soil and water, thereby inducing acute and chronic toxicity in populations worldwide and posing a public health concern 3 . Global estimates suggest that 200 million individuals are affected by As intoxication through contaminated food and water, and occupational exposure 4 …”

ROS‐mediated PERK‐eIF2α‐ATF4 pathway plays an important role in arsenite‐induced L‐02 cells apoptosis via regulating CHOP‐DR5 signaling

“…Apoptosis is one of the important pathophysiological hallmarks of liver aging and age‐related liver diseases 33,34 . Arsenic‐induced apoptosis has been determined in hepatic tissues and primary hepatocytes 15,16 . However, the potential mechanism of that is still unclear and no effective therapeutic agents have been found.…”

“…Epidemiological studies have shown that there is high prevalence of arsenicosis such as skin, 9,10 liver, 11 kidney, 12 lung, 13 and bladder damage 14 . Liver, as one of the important target organs of arsenic toxicity, exhibits an increase of hepatocyte apoptosis in hepatic tissues and primary hepatocytes 15,16 . However, the apoptosis mechanism involved in arsenic poisoning remains unknown.…”