OJHAS Vol. 8, Issue 4: (2009
antioxidant system and oxidative stress in stomach cancer patients with
normal renal and hepatic function
Department of Biochemistry, SV Institute of Medical Sciences, Tirupati, Andhra Pradesh,
V Seshadri Reddy,
Department of Biochemistry, SV Institute of Medical Sciences, Tirupati, Andhra Pradesh,
K Chandra Mouli,
Department of Biotechnology, SV University, Tirupati, Andhra Pradesh,
PVLN Srinivasa Rao,
Department of Biochemistry, SV Institute of Medical Sciences, Tirupati, Andhra Pradesh
Dr. E. Prabhakar Reddy,
Address For Correspondence
Department of Biochemistry,
SV Institute of Medical Sciences,
Tirupati, Andhra Pradesh,
Reddy EP, Reddy VS, Chandra Mouli K, Rao PVLNS. Physiological
antioxidant system and oxidative stress in stomach cancer patients with
normal renal and hepatic function. Online J Health Allied Scs.
Submitted: Oct 8, 2009;
Feb 11, 2010; Published: Apr 30, 2010
Role of free
radicals has been proposed in the pathogenesis of many diseases. Gastric
cancer is a common disease worldwide, and leading cause of cancer death
in India. Severe oxidative stress produces reactive oxygen species (ROS)
and induces uncontrolled lipid peroxidation. Albumin, uric acid (UA)
and Bilirubin are important physiological antioxidants. We aimed to
evaluate and assess the role of oxidative stress (OS) and physiological
antioxidant system in stomach cancer patients. Lipid peroxidation
as plasma Thio Barbituric Acid Reactive substances (TBARS), was found
to be elevated significantly (p=0.001) in stomach cancer compared to
controls along with a decrease in plasma physiological antioxidant
The documented results were due to increased lipid peroxidation and
involvement of physiological antioxidants in scavenging free radicals
but not because of impaired hepatic and renal functions.
Oxidative stress, Lipid peroxidation, Antioxidants, Stomach cancer.
Role of free
radicals has been proposed in the pathogenesis of many diseases
different organs such as breast, gastric, colon, multiple myeloma,
and oral cancer.(1) Gastric cancer is a common disease worldwide and
also one of the leading causes of cancer death (5th in male and 6th
in female) in India. The estimated number of new cases each year is
expected to rise from 10 million in 2000 to 15 million by 2020. Stomach
cancer is the second most frequent cancer in the world.(2) The
of gastric cancer is different throughout the world and 60% of deaths
from gastric cancer occur in developing countries.(3) Severe OS
produces ROS and induces uncontrolled lipid peroxidation. Following lipid
aldehyde products, such as free fatty acids, malondialdehyde (MDA),
occur and those products are referred to as TBARS. Since the cell
consist primarily of lipids, uncontrolled lipid peroxidation can cause
cell injury and death. Considerable evidences have linked oxidative
damage and cancer.
is a normal phenomenon that occurs continuously at low levels in every
individual. Those peroxidation reactions are toxic to cells and cell
membranes; however, they are normally controlled by countervailing
mechanisms. Antioxidants constitute the foremost defense system that
limit the toxicity associated with free radicals. Cells have developed
a comprehensive array of antioxidants that act co-operatively in
vivo to combat the deleterious effects of free radicals. Albumin,
UA and bile pigments such as Bilirubin and biliverdin have also been
proposed as important physiological antioxidants.(4) Roche et al.,
recently reviewed the antioxidant properties of serum albumin.(5) The
present study was planned to evaluate oxidative stress related lipid peroxidation marker MDA as TBARS and Physiological antioxidants in
cancer patients with normal kidney and liver function. Further, we aimed
to assess the role of OS and physiological antioxidant system in stomach
cancer group, compared to control group.
informed consent, 25 cancer patients attending to medical oncology unit,
out patient department of SVIMS, Tirupati were recruited into the study
along with 30 (18m and 12f) healthy controls. All the patients had a
confirmed histological diagnosis and were fresh, untreated cases. Among
25 patients, 20 patients were presented with stomach cancer, 2 patients
with rectum cancer and one each with foot, lung and breast cancer. As
the number was disproportionate for various cancer types, we decided
to include only 20 (15m and 5f) patients with stomach cancer to
the study outcome. The members in control group were recruited from
the healthy persons attending master health checkup Programme of the
hospital and departmental staff. Healthy subjects and patients were
age matched with median age of 45 and 51 years respectively. Exclusion
criteria include active infection, renal failure, diabetes, and
None of the patient or control group participants were alcoholic or
Blood collection and methods
After 12 hour
overnight fasting, heparinised venous blood was collected. Plasma was
separated either to analyze immediately or to store at -800C
until further analysis. CEA was estimated by ELISA using commercial
kits (United Biotech Inc, USA). Urea, Creatinine, and ALT were estimated
by photometric methods using commercial kits on Beckman CX9 Random
clinical chemistry analyzer. Lipid peroxidation marker, MDA levels were
evaluated spectrophotometrically as TBARS.(6)
were performed by using SPSS Statistical Analysis software for Windows
Version 11.5. All data are expressed as mean ±
standard error of mean. To find out the Differences in plasma
of different variables between groups, Mann Whitney U test was used.
P-values of less than .05 were considered to be significant.
antigen (CEA) was observed to be higher in stomach cancer patients as
compared to the controls (P=0.001). Table 1 summarizes the changes in
parameters studied between patient and control groups.
The biochemistries studied in stomach cancer group and their comparison to
||Control Group Median (Mean
Cancer Median (Mean
status of kidney was assessed by measuring urea and creatinine levels.
Creatinine always accurately reflects renal function. In this study,
we report a non-significant change in serum creatinine (p=0.23) between
patient and control groups indicating that the renal function was not
impaired in patient group. The mild increase in urea levels of patients
might be due to pre-renal causes.
was assessed by evaluating serum UA (p=0.052), Bilirubin (p=0.35) and
Alanine transaminase (ALT) (p=0.11) levels in both groups was found to be normal
as we could observe no significant change in these parameters between groups.
stress and physiological antioxidant response
peroxidation measured as TBARS was observed to be significantly
elevated in stomach cancer group compared to healthy controls. The
(significant only for albumin, p=0.001) in all the three physiological
antioxidants viz., Albumin, UA, and Bilirubin was observed in patient group
compared to controls.
of the study suggest that (1) OS in stomach cancer stimulates lipid
peroxidation evidenced by the elevated levels of plasma TBARS, (2)
plasma levels of physiological antioxidants were found in patient group
with normal hepatic and renal function. The documented results were
due to increased lipid peroxidation and involvement of physiological
antioxidants in scavenging free radicals but not because of impaired
hepatic and renal functions.
produced in man during oxygen metabolism, are toxic to cell membranes,
DNA, and RNA and may initiate carcinogenesis.(7) The process of lipid peroxidation is one of the oxidative conversions of polyunsaturated
fatty acids to MDA, the main sensitive parameter of lipid peroxidation.
Elevated plasma TBARS was reported in gastric (8,9) and other cancer
types (10,11) as well.
In the present
case-control study, we report an increase in lipid peroxidation marker
MDA measured as TBARS in stomach cancer patients versus healthy
The difference was statistically found to be significant. Increased
levels of TBARS in our study confirm increased oxidative stress in
cancer patients. Similarly, increased TBARS concentration in both plasma
and erythrocytes of gastric cancer patients was reported recently from
India by Pasupathy et al (12),
who also found higher lipid peroxidation in smoking gastric cancer
than non-smoking patients with gastric carcinoma. This marked increase
in lipid peroxidation may be due to over production of Freeradicals,
excessive generation of lipid peroxidation products in tumor tissue,
and due to impaired antioxidant system that favor accumulation of free
radicals. As renal failure itself is a source of OS, normal renal
observed in our study indicate that increased TBARS might be due to
increased lipid peroxidation, not because of renal failure and decreased
albumin represents the major and predominant antioxidant in plasma,
a body compartment known to be exposed to continuous OS. A large
of total serum antioxidant properties can be attributed to albumin.
Previous works have shown that more than 70% of the free
activity of serum was due to human serum albumin (HSA) (13),
exposed to OS.(14) The N-terminal DAHK sequence is known to
LDL lipid peroxidation and superoxide dismutase-like activity of DAHK/Cu
complex by significantly preventing the formation of ROS was already
reported. Moreover, the reduced Cys34 of albumin has the ability to
scavenge hydroxyl radicals.(15) Highly reactive species are able to
induce oxidative degradation of protein in vitro.(16) Structural modification of albumin induced by glucose or
free radicals impairs its antioxidant properties. Moreover, albumin
is a negative acute phase protein synthesized by liver whose levels
fall in response to infection, injury and neoplasia.(17)
decrease in mean serum albumin levels in colon cancer was reported
by Ko et al.(4) Similarly in stomach cancer patients we demonstrate
a decrease in plasma albumin levels compared to healthy controls.
decrease in plasma albumin levels observed in our study was due to its
protective effects against oxidative attack. In addition, the
status of patient group might partly explain the decreased plasma albumin
UA is a
antioxidant quencher of singlet oxygen as potent as ascorbate and is
potentially more important as an antioxidant in normal physiology.(7)
Little is known about the role of UA for cancer. It has been
that the antioxidant properties of UA may play a crucial role in cancer etiology
by preventing the formation of oxygen radicals, thereby protecting against
Mazza et al
found that UA could protect against cancer by influencing the toxic
and carcinogenic effects of oxygen radicals.(19) Similarly, our study
could demonstrate decrease in plasma UA levels in cancer patients than
in healthy controls, possibly supporting the antioxidant and protective
effect of UA against OS in cancer patients. Ames et al., (7) proposed
that the antioxidant properties of uric acid may act to prevent
of oxygen radicals and thereby protect against carcinogenesis. In
several studies reported that elevated UA levels as a risk factor for
cancer mortality in general populations.(20,21) Recently, Bozkir et
al (22) reported UA levels of lung cancer patients to be significantly
lower than those of healthy controls. There have been reports showing
markedly elevated levels of UA in cancer patients attributed to the malignant
process resulting from the increased nucleic acid turnover in the rapidly
proliferating diseased tissue.(23)
Despite of this
controversy, renal dysfunction would affect the plasma UA levels.
In our study patients presenting normal renal function, decrease in
UA level does not reflect increased renal secretion as a result of
damage. Since there are no enzymes capable of degrading UA in man, the
decrease in plasma of cancer patients must be ascribed to its action
as an in vivo scavenger of oxidants or degradation by radical
and oxidant producing enzymes. Further, serum UA levels might also be influenced
by endogenous production and diet.(24)
its free form and when bound to its physiological carrier protein of
extracellular fluids, albumin, efficiently scavenges radicals.(25)
An indirect antioxidant activity of albumin comes from its ability to
transport bilirubin, which binds with high affinity to the molecule
at Lys240.(26) Such albumin-bound Bilirubin was shown to act as an
inhibitor of lipid peroxidation.(27) Wei et al showed an inverse
between risk of cancer development and serum bilirubin levels.(28) We observed a
decrease but statistically insignificant in fasting plasma bilirubin levels of stomach cancer patients than controls. The
was not statistically significant, presumably because of the low number
of patients involved in the study, which is in line with the
reported by Ko et al in colon cancer.(4) Our findings in stomach
cancer patients indicate that bilirubin exhibits potent antioxidant
properties in counteracting oxidative stress and may contribute to
against oxidative stress-mediated cancer disease.
the increase in oxidative stress in stomach carcinoma was evidenced
by significant rise in plasma lipid peroxidation marker MDA measured
as TBARS. It is interesting to observe that there was a significant
fall in serum albumin level in patients due to its protective effect
against deleterious oxidative damage. It is also interesting to observe
that uric acid and Bilirubin were lowered in these patients, which is
another means of highlighting their protective action in the better
control of oxidative stress. Although the difference between patients
and controls was not statistically significant for UA and Bilirubin,
significant difference might be achieved if larger studies were
The documented results were due to increased lipid peroxidation and involvement
of physiological antioxidants in scavenging free radicals but not because of
impaired hepatic and renal functions. Our study ascertains the importance of
monitoring and controlling OS in carcinoma of stomach.
acknowledge the help and support of Dr. K. Sambasivaiah, Assoc.
Prof. of Oncolgy, in providing samples and clinical material.
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