Send Orders for Reprints to reprints@benthamscience.

ae
Central Nervous System Agents in Medicinal Chemistry, 2015, 15, 99-108 99

Biological Activities of QIAPI 1 as a Melanin Precursor and Its Therapeu-

tic Effects in Wistar Rats Exposed to Arsenic Poisoning

Arturo Solís-Herrera1, Ghulam M. Ashraf2, María del C.A. Esparza1, Ruth I.S. Arias1,
Sergei O. Bachurin3, George E. Barreto4 and Gjumrakch Aliev5,6*

1
Human Photosynthesis Study Center. R & D & I Department, López Velarde 108, Centro, Aguasca-
lientes, Aguascalientes C.P. 20000, México; 2King Fahd Medical Research Center, King Abdulaziz
University, P. O. Box 80216, Jeddah 21589, Saudi Arabia; 3Institute of Physiologically Active Com-
pounds of Russian Academy of Science, Severniy Proezd, 1, Chernogolovka, Moscow Region, 142432,
Russia; 4Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Jave-
riana, Bogotá D.C., Colombia; 5GALLY International Biomedical Research Consulting LLC, 7733
Louis Pasteur Drive, #330, San Antonio, TX, 78229, USA; 6School of Health Science and Healthcare
Administration, University of Atlanta, E. Johns Crossing, #175, Johns Creek, GA, 30097 USA

Abstract: The chemical process initiated by QIAPI 1 has been deemed to be the most important biological reaction asso-
ciated with human photosynthesis, and possibly neuroprotective effects under various inflammatory events. However, the
detailed biological activities of QIAPI 1 as a melanin precursor are still unknown. In the present work, cytotoxicity test
was done by MTT assay to determine cell viability of various cell lines (WI-38, A549, HS 683) like proliferation tests and
its effect on cytokine production. Arsenic poisoning is an often-unrecognized cause of renal insufficiency. No prophylac-
tic and/or therapeutic compounds have shown promising results against kidney diseases. The pathogenesis of Arsenic-
induced nephropathy is not clear. Arsenic, as itself, does not degrade over time in the environment, and its accumulation
may induce toxic effects. In this study, we also report the histological findings of the kidney in 3 groups of Wistar rats, a
control group, a group exposed to arsenic in the water; and a group exposed to arsenic and treated with QIAPI 1 simulta-
neously. The findings of the current evidence indicates a potential therapeutic ability of QIAPI 1.
Keywords: Arsenic, cytotoxicity, human photosynthesis, melanin, QIAPI 1.

INTRODUCTION Arsenic, a naturally occurring metalloid, is a carcino-

Biochemical processes within the human body utilize
water in almost all reactions, and human photosynthesis most
likely influence our capacity to dissociate water, especially
upon onset of a pathological event. Our previous observa-
tions point to an important role of melanin in human cellular
metabolism and energy consumption, and demonstrate that
this compound may be the main fuel in eukaryotic cells
[1, 2].
The chemical process initiated by QIAPI 1, the melanin
precursor, is probably the most important biological reaction
associated with human photosynthesis [1]. QIAPI 1 has
shown interesting results and has been investigated for its
potential protective effects in the last 20 years. For example,
QIAPI 1 protects the brain from various neurological disor-
ders, such as cerebral palsy, and Alzheimer Disease [3]. Al-
though previous reports indicate a potential protective role of
QIAPI 1, further studies are needed to fully address its ef-
fects in the brain.
*Address correspondence to this author at the “GALLY” International Bio-
medical Research Consulting LLC, San Antonio, TX 78229, USA;
Tel: +440-263-7461; E-mails: aliev03@gmail.com; GAliev@uofa.edu
genic compound, and may induce renal failure and kidney
insufficiency in people exposed to its high concentrations [4,
5]. Besides with arsenic being found in water, soil, and air as
a contaminant, it has also been used in chemotherapy for
acute leukemia and other types of tumor [6, 7]. Previous re-
port also indicated that arsenic can be found in Asian tradi-
tional medicine and some homeopathic compounds. For ex-
ample, 1% arsenic trioxide is used to treat skin diseases, such
as eczema and psoriasis, leukemia, and stomatitis [6]. A spe-
cific nutritional role for inorganic arsenic has been uncov-
ered only recently, but animal food has been supplemented
with growth-promoting organic arsenical additives for many
years [8]. Although adaptation to some organic arsenicals
was readily achievable, animals were unable to adapt to the
toxic effects of inorganic arsenic compounds [9] that under-
goes hepatic bio-methylation [10]. As a compound, arsenic is
absorbed through lungs or gastrointestinal (GI) tract, reach-
ing the blood in a few minutes, and up to 70% of its blood
content is eliminated with urine [11, 12].
In this current study, we assessed biological activities of
QIAPI 1 by using cytotoxicity and proliferation tests on cell
cultures. We also report the effect of QIAPI 1 on arsenic-
induced kidney damage using histological evaluation of the
kidney of 3 groups of Wistar rats: a control group, a group

187-/15 $58.00+.00 © 2015 Bentham Science Publishers

100 Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2
exposed to arsenic in the water, and a group exposed to both
the arsenic and QIAPI 1 at the same time.
MATERIALS AND METHODS
Materials
QIAPI 1 was obtained from Dr. Arturo Solis-Herrera,
MD&PhD from Centro de Estudios de la Fotosíntesis Hu-
mana. S.C., Aguascalientes, Mexico.
Experimental Animals
Studies were performed on 2-3 months old Wistar rats
kept in the University of Aguascalientes animal house in
Aguascalientes, Mexico. The animals were kept in cages (5
animals per cage) with unrestricted access to water ad libi-
tum, industrialized food and artificial light for 12 hours daily
cycle. The rats were kept for 10 days prior to experiments.
Animal handling procedures, as well as all experimental
protocols, were approved by the Research and Ethics Com-
mittee of University of Aguascalientes prior the executing
experiments. All procedures were in compliance with Euro-
pean Directive-2010 of FELASA, NIH guidelines to use
animals for research.
Cytotoxicity Test
Cytotoxicity test was performed on 3 cell lines: (a) WI-38
(human diploid cell line from normal embryonic (3 months
gestation) lung tissue, (b) A549 (human lung adenocarcinoma
epithelial cell line), and (c) HS 683 (human neuronal glioma
cell line); and on peripheral blood leukocytes (PBLs) from
10 healthy volunteers (5 male and 5 female at ages 23-45).
The cytotoxicity data was used to calculate LC50 values for
each cell line and PBLs. LC10 and LC5 were also calculated
for PBLs to use these non-toxic concentrations for studies of
QIAPI 1 effects on cytokine release by leukocytes.
Cell viability was determined using the MTT (3-[4,5-
dimethyltiazol-2-yl]-2,5-diphenyltetrazolium bromide)
(Sigma Chemicals Co., USA) test. The MTT is reduced to
formazan by mitochondria. Briefly, the cells (2x105cell/ml)
and leukocytes (2×106 cells/ml) were seeded in 96 well
plates and incubated for 48 h in the presence of 5–0,05
mg/ml of QIAPI 1. After the incubation, cells were treated
with 20 μl of MTT for 90 min. Next, 100 μl sodium dodecyl-
sulfate (SDS) was added to each well and the samples were
allowed to incubate for additional 3h at 37 oC. The optical
density was measured at 570 nm. The optical densities were
normalized to 100% corresponding to optical density of
wells without QIAPI 1 (control wells) and 0% to wells con-
taining no cells (background MTT readout).
Proliferation Tests
Proliferation test was performed on 3 cell lines: WI-38,
A549, and HS 683. 3×104 WI-38 cells and 2×104 A549 and
HS 683 cells were seeded into each wells in 96-wells culture
plates in appropriate culture medium with 10% FBS. Follow-
ing 24 h incubation at 37˚C/5%CO2, medium was removed
and replaced with QIAPI 1 in culture medium at indicated
test concentrations. After 96 h incubation at 37 oC/5% CO2 ,
MTT was added, samples were additionally incubated for
Solís-Herrera et al.
30 min with subsequent addition of SDS and optical density
measurement as described above for the cytotoxicity test. In
this case, the MTT test was used to assess number of cells,
which were proliferating during the 96 h incubation. The
data were normalized to 100% corresponding to optical den-
sity in wells containing cells without QIAPI 1 (control wells)
and 0% to wells containing seeding concentration of the cells
(background MTT readout).
Cytokine Production Test
To assess the effect of QIAPI 1 on cytokine production,
we isolated PBLs as described above. Leukocytes were
treated with selected, nontoxic concentrations of QIAPI 1 (1
mg/ml; 500 μg/ml, 300 μg/ml) with or without 5μg/ml of
lipopolysacharides (LPS). After 24h of incubation at 37 oC/
5%CO2, samples of leukocytes and supernatants were col-
lected. To evaluate the influence of QIAPI 1 on IFN-γ pro-
duction, additional samples were collected after 72 h of in-
cubation.
Cytokines production was assessed using ELISA kits
(BD Biosciences, USA) for human IFNγ, TNF-α, and IL-6
and DuoSet for human IL-3 (R&D Systems, USA) according
to manufacture´s procedures. Cytokines levels were ex-
pressed as pg/ml and read at 450 nm using a Multiskan RC
spectrophotometric reader (Thermo Labsystems, USA).
Arsenic Poisoning and QIAPI 1 Treatment
Rats were randomly assigned into three groups (10 ani-
mals each). Animals in ‘group 1’ did not undergo any addi-
tional treatments and, therefore, were designated as a con-
trol; animals in ‘group 2’ were exposed to water solution of
arsenic (10 mg/l, ad libitum) to “simulate” arsenic “natural
intoxication” in humans through drinking water; animals in
‘group 3’ were exposed to arsenic poisoning similarly to the
animals in the group 2 but with an additional supplementation
of the arsenic-containing water with QIAPI 1 (0.00585938
mg/ml, ad libitum). The variables considered were: basal
urine and blood after arsenic determination, complete blood
count, urinalysis, and mortality. At the end of the experiment
(4 months), animals were killed by decapitation as described
elsewhere for the future histological evaluation of potential
therapeutic effects of QIAPI 1.
Biochemical Analysis
Blood samples were collected each month during the
progress of this experiment. Routine blood tests include
counting the total number of the red (erythrocytes) and white
(leukocytes) blood cells, hematocrit, and hemoglobin levels.
Histopathological Examination
Tissue samples of kidney were collected post-mortally,
stained with hematoxylin and eosin (H&E), and observed
under a light microscope to assess histomorphology of neph-
ron and kidney vasculatures.
Body and Organ Weights
Water solution of arsenic (10 mg/l, ad libitum) and
QIAPI 1 (0.00585938 mg/ml, ad libitum) was used for 4
months. Urine basal levels was discarded because of difficulty
Biological Activities of QIAPI 1 as a Melanin Precursor Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 101

in urine collection. The body weights of rats from each group On the basis of the results of MTT assay for human leuko-
were recorded just before and after the treatments while or- cytes the LC50, LC10 and LC5 were 7 mg/ml (extrapolated),
gan weights (kidney and liver) were measured post-mortally. 1 mg/ml, and 0.5 mg/ml, respectively (Table 2).

Statistical Analysis Table 2. LC of QIAPI 1 for human PBLs.

Data is expressed as mean ± SD of 3 different experi-
ments, and analyzed using One-Way ANOVA followed by Lethal concentration QIAPI 1 [mg/ml]
Dunnet’s post test. A statistically significant difference was
defined at p<0.05. LC50 7.0

LC10 1.0
RESULTS AND DISCUSSION
LC5 0.5
Previous studies report that the administration of QIAPI
1 in Alzheimer patients has shown promising results, as it
may improve memory and cognition, and a few AD people Table 3. Concentrations of QIAPI 1 that inhibit proliferation
have noted bowel and bladder improved control [13, 14]. of cell lines.
Citing the potential effect of QIAPI 1 under various disease
conditions, we first carried out experiments to understand its Concentrations of QIAPI Concentrations of QIAPI
basic biological activities. Firstly, we assessed its possible Cell line 1 inhibit 50% prolifera- 1 inhibit 99% prolifera-
cytotoxicity by using MTT assay. The percentage of viable tion [mg/ml] tion [mg/ml]
cells in the presence of QIAPI 1 was found to be declining
gradually as concentration of QIAPI 1 increased, with ap- WI-38 1.0 4.5
prox. 85%, 60% and 75% cytotoxicity observed at 5 mg/ml A549 2.0 5.5
QIAPI 1 for WI-38 (Fig. 1), A549 (Fig. 2) and HS 683 (Fig.
3) cell line, respectively. Based on this data, LC50 were esti- HS-683 2.0 5.5
mated for each cell line (Table 1). Fig. 4 presents the results
of cytotoxicity test (MTT assay) for human PBLs. Proliferation test of QIAPI 1 was also done on all the
three cell lines. The influence of QIAPI 1 to suppress prolif-
eration capability of the cell lines was found to be increasing
Table 1. LC50 of QIAPI 1 for human cell lines.
gradually with increase of QIAPI 1 concentration, with ap-
proximately 10% viable cells being observed at 5 mg/ml
Cell line LC50 of QIAPI 1 [mg/ml] QIAPI 1 for all three cell lines: WI-38 (Fig. 5), A549 (Fig. 6)
and HS 683 (Fig. 7). Table 3 presents the concentrations of
WI-38 3.0
QIAPI 1 that inhibit proliferation of the cell lines.
A549 4.5 Studies of the effect of QIAPI 1 on TNF-α production in
HS-683 3.5 human leukocytes showed that the compound increased the
level of cytokine production in a dose-dependent manner.
The effect, but not significant, was observed only with un-
The cytotoxicity of QIAPI 1 for human PBLs was found
stimulated human PBLs (Fig. 8). No effect of QIAPI 1 was
to be comparatively lower than for the cell lines, with ap-
observed on IL-6 production by human PBLs (n=10).
proximately 40% cytotoxicity observed at 5 mg/ml QIAPI 1.

Fig. (1). Cytotoxicity test (MTT assay) for WI-38 cell line.
102 Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 Solís-Herrera et al.

Fig. (2). Cytotoxicity of QIAPI 1 for A549 cell line.

Fig. (3). Cytotoxicity of QIAPI 1 for HS-683 cell line.

Fig. (4). Cytotoxicity of QIAPI 1 for human PBLs (n=10).

Biological Activities of QIAPI 1 as a Melanin Precursor Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 103

Fig. (5). Proliferation test of QIAPI 1 for WI-38 cell line.

Fig. (6). Proliferation test of QIAPI 1 for A549 cell line.

Fig. (7). Proliferation test of QIAPI 1 for HS-683 cell line.

104 Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 Solís-Herrera et al.

900

800

700

600
@
O
P

T 500
S
>

˞

)
1 400
7

300

200

100

Mean
0 Mean±Std dev
0 0,3 0,5 1 Mean±Std dev
QIAPI 1 [mg/ml]

Fig. (8). Effect of QIAPI 1 on spontaneous TNF-α production by human PBLs (n=10).

70

60

50

40

@
O
P

T 30
S
>

ˠ

1
)
,
20

10

-10
Mean
Mean±Std err
-20 Mean±Std dev
0+LPS 0,3+LPS 0,5+LPS 1+LPS
QIAPI 1 [mg/ml]

Fig. (9). Effect of QIAPI 1 on IFN-γ production after LPS stimulation by human PBLs (n=10). Results after 24h of incubation.

Studies of the effect of QIAPI 1 on IFN-γ production
showed that incubation with QIAPI 1 for either 24h (Fig. 9)
or 72h (Fig. 10) strongly decreased, in a dose-dependent
manner, the level of interferon production in response to
LPS-induced stimulation.
We also determined the potential therapeutic effect of
QIAPI 1 on Wistar rats exposed to arsenic via the drinking
water. It has been well documented that the arsenic exposi-
tion can cause toxic effects to the brain, and peripheral or-
gans [15]. Of special importance, the kidney is considered as
main target of arsenic, as this compound can cause insuffi-
ciency and renal failure, and normal physiological kidney
functioning is essential for arsenic biotransformation and
excretion [5, 16]. We observed the presence of cortex or me-
dulla and number of glomeruli and vessels by staining frozen
sections with H&E [5]. Major kidney alterations include
structural abnormalities of nephron and vascular membranes
and heavy deposition of abnormal flak-like materials [5].
Biological Activities of QIAPI 1 as a Melanin Precursor Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 105

300

250

200

@
O
P 150

T
S
>

ˠ
IFN-

100

50

Mean
-50 Mean±Std err
0+LPS 0,3+LPS 0,5+LPS 1+LPS Mean±Std dev
QIAPI 1 [mg/ml]

Fig. (10). Effect of QIAPI 1 on IFN-γ production after LPS stimulation by human PBLs (n=10). Results after 72h of incubation.

Fig. 11 shows the renal anatomo-histological features of rat Table 4. Comparison of differences in statistical analyses
group 1, which served as control and was not exposed to values of adrenal glands weight before and after
arsenic or QIAPI 1. Tissue edema and hemorrhage were seen treatment with QIAPI 1.
in rat group 2 exposed to arsenic (Fig. 12). The significant
difference can be observed clearly by comparing them with
control group kidney (Fig. 11). These findings suggest pres- Adrenal glands weights Control (mg) Treated (mg)
ence of an arsenic-induced damage in renal tissue, which is
Mean 17.7 24.428
mainly attributable to the altering multiple metabolic path-
ways through uncoupling of oxidative phosphorylation [17]. Sample Size 9 7
In this context, previous studies support the idea of a reactive
SD 1.791 7.057
oxygen species (ROS) mediated damage to kidney, which
might explain the toxicity induced by arsenic exposition SEM 0.5970 2.667
[18]. The epithelial cells of proximal convoluted tubules are
Median 17.40 23.300
found to be more sensitive to arsenic-induced toxicity due to
their highest filtration and reabsorptive activity and anatomi- Lower 95 % 16.323 17.902
cal positions as the first renal tubular epithelial cells to be
Upper 95 % 19.077 30.955
exposed to filtered toxicants [5, 19]. From a systemic toxic-
ity induced by arsenic, this may include renal failure and Minimum 15.600 12.500
kidney cortical and tubular necrosis [20, 21].
Maximum 21.400 36.200
In kidney failure patients, QIAPI 1 has been reported to
protect kidney and showed remarkable improvements up to Mean difference 6.729 6.729
80% [22]. QIAPI 1 also showed remarkable response in cir-
2.773 with 14
rhotic liver, boosted by liver’s natural tendency of regenera- t
degrees of freedom
tion [22]. These earlier reported findings have been further
strengthened by the findings of current study. In rat group 3, P value 0.0149
when rats were treated with QIAPI 1 simultaneously with
F value 15.526
arsenic, Bowman's space was found to be reduced, suggest-
ing a marked reduction in fibrosis and retraction of glomeru-
lus (Fig. 13). Bleeding was also found to be decreased sig- Organ weights of rats were determined after treatment
nificantly. The tissue edema and hemorrhage observed in rat with water solutions of arsenic and QIAPI 1 ad libitum.
group 2 exposed to arsenic was also found to be decreased Table 4 and Table 5 represent the results of detailed statisti-
significantly in rats exposed to arsenic and treated simulta- cal analyses on the weights of adrenal glands and spleen,
neously with QIAPI (Fig. 13). These findings suggest thera- respectively. The mean weight of adrenal glands was found
peutic potential effects of QIAPI 1. to be significantly enhanced by 38% in treated rats (P<0.05),
106 Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 Solís-Herrera et al.

5X 10X

40X 100X
Fig. (11). Control group, kidney, Hematoxylin and Eosin (H&E) count-staining, at different resolutions shows intact morphology.

5X 10X

100X

Fig. (12). Arsenic exposed group, kidney, H & E staining at different resolutions shows severely damages that accompanies with the presence
of a large sized edematous structures throughout kidney tissues (indicated by arrows).

(Table 4). The mean weight of spleen was found to be
slightly reduced by 16% in treated rats (Table 5). These re-
sults show that the effect of arsenic and QIAPI 1 is not uni-
form and varies from organ to organ. The physiological
make up and biological functions of different organs play
vital role on the nature of effect induced by arsenic and/or
QIAPI 1.
We also assessed the blood constituents in animals ex-
posed to arsenic and arsenic+QIAPI 1 combination. Our re-
sults indicated a tendency, but not statistically significant,
effect of the QIAPI 1 treatment on red blood cells of animals
exposed to arsenic. Similar effects were observed in the he-
moglobin and in white blood cells numbers (Table 6).
Biological Activities of QIAPI 1 as a Melanin Precursor Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2 107

Table 5. Comparison of differences in statistical analyses values of spleen weight before and after treatment with QIAPI 1

Spleen Weights Control (mg) Treated (mg)

Mean 272.777 228.849

Sample Size 9 6

SD 59.698 86.725

SEM 19.899 35.405

Median 269.90 210.25

Lower 95 % CI 226.89 137.82

Upper 95% CI 318.67 319.88

Minimum 345.40 386.10

Maximum 345.40 386.10

Mean difference -43.928

t 1.169 with 13 degrees of freedom

Two-tailed P value 0.2365

F 1.898

Table 6. Blood analysis of animals exposed to arsenic alone, and in combination with QIAPI 1 treatment (Q1).

Type of Blood Cells Control Arsenic Arsenic + Q1

Red blood cells 4,754,000±669,674 5,146,000±671,315 4,192,000±1,528,690

White blood cells 83,200±15,841 114,200±24,911 106,600±36,903
Eos 1 1,6±0,489 1,5±0,5
Seg 36,4±10,480 39,2±12,237 35,4±8,428
Lym 62±9,757 58,2±11,822 62±7,899
Mon 2 1 2±0,816
Hematocrit 43,97±1,652 46,08±3,407 45,34±2,270
Hemoglobin 0,342±0,013 0,360±0,021 0,345±0,016

5X 10X

40X 100X

Fig. (13). Arsenic exposed group animals which are simultaneously treated with QIAPI 1, H & E, staining at different resolutions shows pres-
ence of non-significant alterations throughout kidney tissues (indicated by single arrows).
108 Central Nervous System Agents in Medicinal Chemistry, 2015, Vol. 15, No. 2
The findings of the current study indicate potential thera-
peutic effects of QIAPI 1 in vitro and in vivo conditions.
Future implication of the QIAPI 1 in the context of the non-
curable human diseases, such as neurodegenerative illnesses,
deserves special attention.
CONFLICT OF INTEREST
The author(s) confirm that this article content has no con-
flict of interest.
ACKNOWLEDGEMENTS
This work was supported by Human Photosynthesis
Study Center, Aguascalientes, México and GALLY Interna-
tional Biomedical Research Consulting LLC, San Antonio,
Texas, USA. Dr. Ghulam Md Ashraf was supported by King
Fahd Medical Research Center (KFMRC), King Abdulaziz
University, Jeddah, Saudi Arabia. G.E. Barreto works is sup-
ported by Pontificia Universidad Javeriana. We also very
thankful for Ms. Galina Alieva editorial works during the
preparation of this paper.
REFERENCES
[1] Solis-Herrera, A.; Arias Esparza, M.d.C.; Solis Arias, R.I.; Solis
Arias, P.E.; Solis Arias, M.P. The Pharmacologic Intensification of
the Water Dissociation Process, or Human Photosynthesis, and its
effect over the Recovery Mechanisms in Tissues Affected By
Bloodshed of Diverse Etiology. Int. J. Clinic. Med., 2011, 2, 332-
338.
[2] Solis-Herrera, A.; Arias-Esparza, M.d.C. The unexpected capacity
of melanin to dissociate water molecule is a new way to improve
mitochondrial cytopathies. Mitochondrion, 2010, 10, 200-201.
[3] Herrera, A.S.; Leszek, J.; del Carmen Arias Esparza, M.; Solís-
Arias, R.I.; Solís-Arias, P.E.; Solís-Arias, M.P. Human
Photosynthesis and Alzheimer’s Disease. Pharmaceut. Anal. Acta.,
2012, 1, 15.
[4] Pott, W.A.; Benjamin, S.A.; Yang, R.S. Pharmacokinetics,
metabolism, and carcinogenicity of arsenic. Rev Environ Contam
Toxicol, 2001, 169, 165-214.
[5] Rizwan, S.; Naqshbandi, A.; Farooqui, Z.; Khan, A.A.; Khan, F.
Protective effect of dietary flaxseed oil on arsenic-induced
nephrotoxicity and oxidative damage in rat kidney. Food Chem.
Toxicol., 2014, 68(99-107).
[6] Hughes, M.F.; Beck, B.D.; Chen, Y.; Lewis, A.S.; Thomas, D.J.
Arsenic Exposure and Toxicology: A Historical Perspective.
Toxicol. Sci., 2011, 123(2), 305-332.
Received: March 14, 2015 Revised: April 14, 2015 Accepted: April 20, 2015
DISCLAIMER: The above article has been published in Epub (ahead of print) on the basis of the materials provided by the author. The Edito-
rial Department reserves the right to make minor modifications for further improvement of the manuscript.
Solís-Herrera et al.
[7] Tallman, M.S.; Altman, J.K. How I treat acute promyelocytic
leukemia. Blood, 2009, 114(25), 5126-5135.
[8] Pollutants, N.R.C.C.o.M.; Biological Effects of, E. Distribution of
Arsenic in the Environment. 1977.
[9] Koestler, D.C.; Avissar-Whiting, M.; Houseman, E.A.; Karagas,
M.R.; Marsit, C.J. Differential DNA methylation in umbilical cord
blood of infants exposed to low levels of arsenic in utero. Environ.
Health Perspect., 2013, 121(8), 971-977.
[10] Kojima, C.; Ramirez, D.C.; Tokar, E.J.; Himeno, S.; Drobna, Z.;
Styblo, M.; Mason, R.P.; Waalkes, M.P. Requirement of Arsenic
Biomethylation for Oxidative DNA Damage. J. Natl. Cancer Inst.,
2009, 101(24), 1670-1681.
[11] Chen, D.S.-J.; Yan, D.X.-J.; Chen, D.Z. In Encyclopedia of
Metalloproteins. Kretsinger, R.H.; Uversky, V.N.; Permyakov,
E.A., Eds.; Springer New York, 2013, pp 135-138.
[12] Rose, J. Environmental Toxicology, CRC Press, 2003.
[13] Herrera, A.S.; Carmen Arias Esparza, M.D.; Ashraf, G.M.;
Zamyatnin, A.A.; Aliev, G. If the Mitochondria were not the
Energy Source of the Cell, as would be the Cell Biology?.
CNSAMC, 2015, 15(1), 32-41.
[14] Aliev, G.; Solís-Herrera, A.; Li, Y.; Kaminsky, Y.G.; Yakhno,
N.N.; Nikolenko, V.N.; Zamyatnin, A.A.; Benberin, V.V.;
Bachurin, S.O. Human photosynthesis, the ultimate answer to the
long term mystery of Kleiber’s law or E= M 3/4: Implication in the
context of gerontology and neurodegenerative diseases. Open J.
Psychiat., 2013, 3(4), 408-421.
[15] Tchounwou, P.B.; Patlolla, A.K.; Centeno, J.A. Carcinogenic and
systemic health effects associated with arsenic exposure--a critical
review. Toxicol. Pathol., 2003, 31(6), 575-588.
[16] Waalkes, M.P.; Liu, J.; Ward, J.M.; Diwan, B.A. Mechanisms
underlying arsenic carcinogenesis: hypersensitivity of mice
exposed to inorganic arsenic during gestation. Toxicology, 2004,
198(1-3), 31-38.
[17] Sharma, B.; Singh, S.; Siddiqi, N.J. Biomedical Implications of
Heavy Metals Induced Imbalances in Redox Systems. BioMed Res.
Intern., 2014, 2014:640754. doi: 10.1155/2014/ 640754.
[18] Thomson, V.S.; Narayanan, K.; Singh, J.C. Contrast induced
nephropathy in urology. Indian J. Urol., 2009, 25(4), 437-445.
[19] Peraza, M.A.; Cromey, D.W.; Carolus, B.; Carter, D.E.; Gandolfi,
A.J. Morphological and functional alterations in human proximal
tubular cell line induced by low level inorganic arsenic: evidence
for targeting of mitochondria and initiated apoptosis. J. Appl.
Toxicol., 2006, 26(4), 356-367.
[20] Gerhardt, R.E.; Hudson, J.B.; Rao, R.N.; Sobel, R.E. Chronic renal
insufficiency from cortical necrosis induced by arsenic poisoning.
Arch. Intern. Med., 1978, 138(8), 1267-1269.
[21] Medicine, C.o.C.D.i.E.; Medicine, I.o. Environmental Medicine:
Integrating a Missing Element into Medical Education. National
Academies Press, 1995.
[22] Solís-Herrera, A.; del Carmen Arias Esparza, M.; Solis Arias, M.P.
The pharmacological modulation of human photosynthesis: A real
hope for Bhopal, India. J. Res. Enviro. Sci. Tech., 2013, 2(7), 136-
146.