Texas Journal of Microscopy - Texas Society for Microscopy

months [23] . The presence of As can disrupt the hepatic and
renal enzymatic activity of catalase [44] , copper/zinc superoxide
dismutase (Cu/Zn SOD) [72] , glutathione (GSH) [44] , glutathione
reductase (GR) [44] , glucose-6-phosphate (G6P) [44] ,
glutathione transferase (GST) [44,57] , glucose-6-phosphate
dehydrogenase (G6Pdh), Na+/K+ ATPase [40,56] , nicotinamide
adenine dinucleotide (NAD+) [6,16] , and pyruvate
dehydrogenase (Pyr-dh) [54] . Other cellular effects include
apoptosis, cell proliferation, cellular growth, chromosomal
aberrations [7,39,43] , DNA demethylation [73] , DNA replication
and DNA repair [7,43] , DNA strand breaks [7,13] , genotoxicity,
mutagenesis, and phosphate substitution [2,7,20,21,24,26,33] .
3. Pathology of Arsenic Toxicity in Humans
Morphological and immunohistochemical effects of As
have been documented in tissues at both the histological and
ultrastructural levels. In general, As causes widespread endothelial
cellular toxicity, resulting in capillary damage and
tissue hypoxia [10] . Effects of arsenic damage to skin, gastrointestinal,
cardiac, bone marrow, central nervous system,
liver, pancreatic, gonadal, and renal tissues may be noticed
at different stages of poisoning, particularly during chronic
exposure [10].
3.1 Liver Pathology
In 1786, the tonic Fowler’s solution (KH 2AsO 4) was developed
to treat psoriasis, an immune-mediated disease affecting
the skin. The disease manifests as red scaly patches
called plaques that are produced by excessive skin cell production
and inflammation. It has been documented that in
humans, prolonged use of Fowler’s solution in therapeutic
doses caused hepatic ascites, non-cirrhotic portal hypertension,
fibrosis, and cirrhosis [17] . Human liver fibrosis, cirrhosis
and hepatoportal sclerosis due to As toxicity have been
demonstrated to be linked to the disruption of the homeostasis
of collagen, 4-hydroxyproline, phospholipids, cholesterol,
and fatty acids [12] . Hepatic fibrosis is believed to develop
from the oxidative stress induced by As [38] .
Arsenical chemotherapeutic agents are used for the treatment
of cancers such as chronic myeloid leukemia and
Hodgkin’s disease [58,59] . Both therapies have been documented
to produce mild hepatic sclerosis, perisinusoidal fibrosis,
portal triad fibrosis and narrowing of portal venules [59] .
Figure 1. Light micrograph of liver portal triad containing a
bile duct (top arrow) and the hepatic artery (bottom arrow)
but no distinguishable portal vein due to increased fibrosis.
(With permission from Journal of Clinical Pathology [59] ).
46 Tex. J. Micros. 37:2, 2006
Figure 1 shows a light micrograph of As induced portal fibrosis
in a human patient who was receiving chemotherapy.
In Figure 2, collagen inclusions between the endothelium
and a hepatocyte are shown in an electron micrograph from
a human patient [59] . Generated reactive oxygen species from
oxidation reactions react with cellular lipids to produce a
number of reactive aldehydes, which stimulate the synthesis
of collagen mRNA. This toxic effect has been documented
Figure 2. TEM of liver showing collagen deposits (arrow) between
the endothelium and a hepatocyte in the space of Disse.
(With permission from Journal of Clinical Pathology [59] ).
for arsenic, ethanol, copper, and iron, in which the lipid peroxidation
produces free radicals that induce an excess of
collagen deposition [12] .
Prolonged human consumption of drinking water contaminated
with 0.05 mg/L of arsenic in West Bengal has
demonstrated hepatic pathology including hepatomegaly,
non-cirrhotic portal fibrosis, and a small number of cases
with portal hypertension [17] . It appears that in humans the
most compromising liver damage from arsenic toxicity involves
hepatomegaly, non-cirrhotic portal hypertension, and
jaundice [18,22,47] . Jaundice, a yellowing of the skin, sclera and
mucous membranes caused by increased levels of bilirubin,
may evolve into cirrhosis, which may be accompanied by ascites,
especially after prolonged arsenical medication [18,22] .
3.2 Arsenic and Diabetes
Epidemiological reports have suggested correlations between
the chronic consumption of water contaminated with
As and the incidence of Type 2-diabetes, primarily in Bangladesh,
Sweden, and Taiwan [31,41,51,52,53,67,68] . However, Navas-Acien
et al. (2005) concluded that there is inadequate
experimental and epidemiological evidence to demonstrate
causality between arsenic consumption and the onset of
Type 2 diabetes mellitus [46] . Further research is needed.
3.3 Other Pathological Characteristics
Blood samples from arsine-exposed individuals showed
increased hematocrit, a decreased hemoglobin concentration
to