Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague–Dawley rats

Abstract

Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.

An Overview of Carcinogenic Heavy Metal: Molecular Toxicity Mechanism and Prevention

“… 35 , 36 Hepatic function is also disrupted by As toxicity because of cross-linking with enzymes and oxidative DNA damage in rats. 37 …”

Carnosic Acid‐combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model

“…Arsenic exposure significantly increased the activities of plasma alanine aminotransferase (glutamate pyruvate transaminase) and aspartate aminotransferase (glutamate oxaloacetate transaminase), as well as the number of structural chromosomal aberrations and frequency of micronuclei in bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced .…”

“…well as the number of structural chromosomal aberrations and frequency of micronuclei in bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced [23].…”

Restorative Effects of Zingiber Officinale on Arsenic-Induced Genotoxic Effects in Chromosomal Structure of Mice

“…During the maturation process, the erythroblast develops into a polychromatic erythrocyte; the nucleus undergoes extrusion and MN persisting in enucleated cytoplasm can be detected using specific staining processes. The mean value of MN in control group was 41.00±9.74 and in arsenic-treated group was 183.4±27.74 which showed a statistically significant (p<0.01) elevation in comparison to [5].…”

“…The trivalent arsenite is more toxic than pentavalent arsenate. The trivalent form has higher affinity for thiol group, and it is more cytotoxic and genotoxic [5].…”