Ranjana Singh

Implications of free radicals and antioxidant levels in carcinoma of the breast: A never-ending battle for survival

BACKGROUND Under normal circumstances, there is a steady balance between the production of oxygen derived free radicals and their destruction by the cellular antioxidant system inside the human body. However, any imbalance between the levels of these oxidants and antioxidants might cause DNA damage and may lead to cancer development. The aim of this study was to evaluate the level of antioxidants and free radicals in blood and tissue of cancer patients and compare these levels at different TNM stages to derive the possible role of free radicals and antioxidant enzymes in the etiology of breast cancer. MATERIALS AND METHODS This study includes 30 patients suffering from cancer breast and 20 patients as controls who had benign breast diseases. Circulating lipid peroxide (Malonyldialdehyde [MDA]) levels and activities of the defensive enzymes (Superoxide Dismutase [SOD] and Catalase [CAT]) were estimated in the blood and breast tissue of these patients. RESULTS Increased levels of free radicals and low levels of antioxidants were observed in malignant tissue. An elevated lipid peroxide concentration was found in the tissue of all the cancer breast patients as evidenced by an increase in the mean MDA level seen with increasing TNM stage of carcinoma breast. Levels of antioxidants SOD and CAT were decreased in cancer patients. CONCLUSION The results of our study suggest that free radical activity is enhanced in cancer breast patients while the antioxidant defense mechanism is weakened. This activity is enhanced with the increasing severity of cancer as depicted in different TNM stages of breast cancer.

Chronomics of circulating plasma lipid peroxides and anti-oxidant enzymes and other related molecules in cirrhosis of liver. In the memory of late Shri Chetan Singh.

BACKGROUND The chronome (from chronos, time, and nomos, rule; time structure) of lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy and management of preventive and curative chronotherapy. PATIENTS AND METHODS Thirty patients with liver cirrhosis, 25-45 years of age, and 60 age-matched clinically healthy volunteers were synchronized for 1 week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect the free-radical system were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, presumably 24-h synchronized conditions. Determinations included plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, and serum total protein, albumin, ascorbic acid, and uric acid concentrations. RESULTS A marked circadian variation was demonstrated for each variable in each group by population-mean cosinor (P < 0.01). In addition to anticipated differences in overall mean value (MESOR), patients differed from healthy volunteers also in terms of their circadian pattern. CONCLUSION Mapping the broader time structure (chronome) with age and multifrequency rhythm characteristics of antioxidants and pro-oxidants is needed for exploring their putative role as markers in the treatment and management of liver cirrhosis.

Hypolipidemic activity of Anthocephalus indicus (kadam) in hyperlipidemic rats

The hypolipidemic action of Anthocephalus indicus (family, Rubiaceae: Hindi name, Kadam) fruit extract has been studied in hyperlipidemic rats fed a triton- and cholesterol-rich high-fat diet. In triton WR-1339-induced hyperlipidemic rats, feeding with the fruit extract (500 mg/kg b.w.) exerted a lipid-lowering effect as assessed by reversal of plasma levels of total cholesterol, phospholipids, and triglyceride following reactivation of the post-heparin lipolytic activity. In another model, chronic feeding of this natural product (500 mg/kg, b.w.) to animals simultaneously fed a high-fat diet for 30 days caused lowering of lipid levels in plasma and liver accompanied with stimulation of hepatic lipolytic activity. The hypolipidemic activity of Anthocephalus indicus fruit extract iscompared with guggulipid, a known lipid-lowering drug, in both models.

Oxidative stress and antioxidant status in patients with chronic myeloid leukemia.

Chronic myeloid leukemia is a myeloproliferative disorder with a unique rearrangement, the Philadelphia chromosome. Oxidative stress, a pervasive condition of an increased number of reactive oxygen species, is now recognized to be prominent feature of various diseases and their progression. Thus antioxidants, which control the oxidative stress state, represent a major line of defense regulating overall true state of health. The relationship between antioxidants status and levels of well-known markers of oxidative stress that are measured as lipid peroxides and oxidized proteins reflect better health indices and postures. The aim of this study was to evaluate the role of oxidative stress in pathophysiology of Chronic myeloid leukemia by measuring the circulating plasma lipid peroxide levels in terms of malonyldialdehyde, total lipid hydroperoxide and oxidized proteins as protein carbonyl whereas antioxidant status were estimated in terms of reduced glutathione and total thiol in plasma of Chronic myeloid leukemia patients. The present study included 47 Chronic myeloid leukemia patients and 20 age-and sex-matched healthy subjects. Out of 47 Chronic myeloid leukemia patients, 31 were in chronic phase (CML-CP) and 16 in accelerated phase (CML-AP). The median age of Chronic myeloid leukemia patients was 33 years and that of controls was 32 years. Oxidative stress and antioxidant status in plasma were evaluated by spectrophotometric procedures. There was a significant increase (p<0.05) in plasma malonyldialdehyde, total lipid hydroperoxide and protein carbonyl levels in Chronic myeloid leukemia patients as compared to healthy subjects. Our results also showed that plasma malonyldialdehyde and protein carbonyl levels were markedly elevated (p<0.05) in both chronic phase (CML-CP) and accelerated phase (CML-AP) as compared to healthy volunteers. Antioxidant status was found to be significantly decreased (p<0.05) in Chronic myeloid leukemia patients and its phases as compared to healthy participants. It could be concluded that oxidative stress may be associated with the pathophysiology of Chronic myeloid leukemia.

Lipid Lowering Activity of Anthocephalus indicus Root in Hyperlipidemic Rats

The lipid lowering activity of Anthocephalus indicus (family Rubiaceae; Hindi name Kadamba) root extract has been studied in triton WR-1339 induced hyperlipidemia in rats. In this model, feeding with root extract (500 mg kg−1 b.w.) lowered plasma lipids and reactivated post-heparin lipolytic activity in hyperlipidemic rats. Furthermore, the root extract (50–500 μM) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems, in vitro. The results of the present study demonstrated both lipid lowering and antioxidant activities in root extract of A. indicus, which could help prevention of hyperlipidemia and related diseases.

Studies on biomarkers for oxidative stress in patients with chronic myeloid leukemia.

BACKGROUND Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a unique genetic rearrangement, the Philadelphia chromosome. High reactive oxygen species (ROS) levels favor oxidative stress, which could play a vital role in normal processes and various pathophysiologies including neoplasm. Biomarkers of oxidative stress are measured as products of oxidized proteins and lipids. Plasma levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and total lipid hydroperoxide (LOOH) were used as biomarkers of oxidative stress in the past. The aim of this study was to evaluate the products of protein oxidation and lipid peroxidation in plasma as biomarkers of oxidative stress in CML patients. PATIENTS AND METHODS The study included 40 CML patients and 20 age- and sex-matched healthy volunteers. Of 40 CML patients, 28 were in chronic phase (CML-CP) and 12 in accelerated phase (CML-AP). Plasma levels of PC, TBARS and LOOH as biomarkers of oxidative stress were evaluated by spectrophotometric methods. RESULTS There were significant differences (P < .05) in plasma levels of PC, TBARS and LOOH in CML, CML-CP and CML-AP patients as compared to controls. CONCLUSION PC, TBARS and LOOH might reflect oxidative stress in CML patients and might be used as biomarkers in such patients.

Circadian periodicity of plasma lipid peroxides and anti-oxidant enzymes in pulmonary tuberculosis.

The circadian periodicity of plasma lipid peroxide levels and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were studied in 50 clinically, bacteriologically and radiologically proven fresh cases of pulmonary tuberculosis (age: 21–45 years) and 60 age-matched healthy volunteers with diurnal activity from 06∶00 to about 22∶00 and nocturnal rest. A marked circadian variation in plasma lipid peroxide level was recorded in healthy subjects and pulmonary tuberculosis patients with significant amplitude and acrophase around 16∶21 and 17∶12 respectively. The acrophase tended to be delayed in tuberculosis patients. Furthermore, a statistically significant circadian rhythm was found in SOD, CAT and GPx activities in normal volunteers and pulmonary tuberculopsis patients. SOD and CAT enzyme activity was noted to be maximum at 06∶00 and minimum at 00∶00 in tuberculosis patients. The circadian acrophase for GPx activity was recorded at 16∶15 in normals and around 22∶45 in patients. Moreover, the activity was found to be decreased at all sampling hours during 24-hours sleep-awake period in patients in comparison to healthy counterparts. The MESOR and circadian amplitude also decreased markedly. The decreased activity of measured antioxidant enzymes in pulmonary tuberculosis patients could probably be associated with oxidative stress and/or decreased anti-oxidant defensive mechanism in such patients.

Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians

The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16-75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16-30, 31-45, 46-60 and 61-75 years of age, comprising 20, 20, 15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study.

Hypoglycemic, lipid lowering and antioxidant activities in root extract of Anthocephalus indicus in alloxan induced diabetic rats.

The present study was carried out to evaluate the hypoglycemic, lipid lowering and antioxidant activities in root extract of Anthocephalus indicus (A indicus) in alloxan inducd diabetic rats. Oral administration of ethanol extract of root (500mg/ kg body weight) for 21 days resulted in significant decrease in the levels of blood glucose, triglycerides, total cholesterol, phospholipid and free fatty acids. Furthermore, the root extract (100–400μg) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems, in vitro. The result of the present study demonstrated hypoglycemic, lipid lowering and antioxidant activities in root extract of A indicus, which could help in prevention of diabetic dyslipidemia and related diseases.

Opportunity of detecting pre-hypertension : worldwide data on blood pressure overswinging

Overswinging or CHAT (brief for Circadian Hyper-Amplitude-Tension), that is an excessive circadian variation in blood pressure (BP), has been associated with a large increase in cardiovascular disease risk, present even in the absence of an elevated BP itself. This usually asymptomatic condition is usually overlooked by current practice based on spot-checks, because to be diagnosed, measurements need to be taken around-the-clock, preferably for 7 days at the outset. Once diagnosed, however, a usual circadian BP pattern can be restored by means of certain non-pharmacologic or pharmacologic interventions timed appropriately. Thereby, it is possible to reduce the risk of cardiovascular morbidity and mortality, cerebral ischemic events and nephropathy in particular. For the preparation of guidelines regarding the diagnosis of BP disorders and for the institution of primary as well as secondary preventive measures, it is important to know what the incidence of CHAT is on a global basis. We found 191 cases of CHAT among 1602 mostly 7-day/24-h BP profiles, obtained from several centers in different countries participating in an ongoing project on the BIOsphere and the COSmos (BIOCOS). CHAT incidence is about the same between men and women, but it is diagnosed more often among patients with borderline hypertension or with glucose intolerance. It is also more common among MESOR-hypertensive than among MESOR-normotensive individuals. Priority should be given to the development of an unobtrusive and affordable device to automatically monitor BP and to analyze the data as-one-goes, so that cardiovascular disease risk can be prevented.