Raj Kumar Singh

Effect of herbal hypoglycemic agents on oxidative stress and antioxidant status in diabetic rats

In the present study the antioxidative potential ofMomordica charantia, Azadirachta indica, Allium sativum andOcimum sanctum was assessed in streptozotocin induced diabetic rats. Lipid peroxide levels were also measured in normal, diabetic and treated animals. Malondialdehyde (MDA) levels were significantly higher and antioxidant activity was found low in diabetic groups as compared to the control groups, and significant alteration in both the MDA levels and antioxidant activity was also observed when the above herbal hypoglycemic agents were given to diabetic rats. On the basis of our results we conclude thatM. charantia, A. indica, A. sativum andO. sanctum are not only useful in controlling the lipid peroxide levels but are also helpful in further strengthening the antioxidant potential.

Effect of Indian Herbal Hypoglycemic Agents on Antioxidant Capacity and Trace Elements Content in Diabetic Rats

In the present investigation we report the protective potential of some herbal hypoglycemic agents on antioxidant status and levels of metal ions in streptozotocin-induced diabetic rats. Furthermore, in vitro antioxidant activity of the herbs was also evaluated. Induction of diabetes mellitus in rats caused an increase in blood lipid peroxide levels that was associated with the reduced activity of red blood cell (RBC) antioxidant enzymes--namely, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase--along with depletion of plasma reduced glutathione (GSH) and copper, zinc, iron, magnesium, and selenium levels. Oral treatment of diabetic rats with Allium sativum, Azadirachta indica, Momordica charantia, and Ocimum sanctum extracts (500 mg/kg of body weight) not only lowered the blood glucose level but also inhibited the formation of lipid peroxides, reactivated the antioxidant enzymes, and restored levels of GSH and metals in the above-mentioned model. The herbal extracts (50-500 microg) inhibited the generation of superoxide anions (O(2)(-.)) in both enzymatic and nonenzymatic in vitro systems. These preparations also inhibited the ferrous-sodium ascorbate-induced formation of lipid peroxides in RBCs. The in vivo and in vitro protective effects of the above-mentioned herbal drugs were also compared with that of glibenclamide. On the basis of our results, we conclude that the above-mentioned herbal plants not only possess hypoglycemic properties, but they also decrease oxidative load in diabetes mellitus. Therefore, we propose that long-term use of such agents might help in the prevention of diabetes-associated complications. However, the extrapolation of these results to humans needs further in-depth study.

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.

BACKGROUNDnThe 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.nnnPATIENTS AND METHODSnThirty 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.nnnRESULTSnA 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.nnnCONCLUSIONnMapping 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.

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.

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.

Effect of gender, age, diet and smoking status on chronomics of circulating plasma lipid components in healthy Indians

BACKGROUNDnCirculating lipid components were studied under near-normal tropical conditions (around Lucknow) in 162 healthy volunteers - mostly medical students, staff members and members of their families (103 males and 59 females; 7 to 75y), subdivided into 4 age groups: A (7-20y; N=42), B (21-40y; N=60), C (41-60y; N=35) and D (61-75y; N=25).nnnMETHODSnBlood samples were collected from each subject every 6h for 24h (4 samples). Plasma was separated and total cholesterol, high-density-lipoprotein (HDL) cholesterol, phospholipids and total lipids were measured spectrophotometrically. Data from each subject were analyzed by cosinor. We examined by multiple-analysis of variance how the MESOR (Midline Estimating Statistic Of Rhythm, a rhythm-adjusted mean) and the circadian amplitude of these variables is affected by gender, age, diet (vegetarian vs. omnivore), and smoking status.nnnRESULTSnIn addition to effects of gender and age, diet and smoking were found to affect the MESOR of circulating plasma lipid components in healthy Indians residing in northern India. Age also affected the circadian amplitude of these variables.nnnCONCLUSIONnThese results indicate the possibility of using non-pharmacological interventions to improve a patients metabolic profile before prescribing medication under near normal tropical conditions. They also add information that may help refine cut-off values in the light of factors shown here to affect blood lipids.

Circadian Periodicity of Circulating Plasma Lipid Peroxides, Uric Acid and Ascorbic Acid in Renal Stone Formers

AbstractCircadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric acid levels were studied in one hundred renal stone formers (55 women and 45 men; age 20–60 years) and 50 clinically healthy volunteers (21 women and 29 men; age 21–45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A marked circadian variation was demonstrated by population-mean-cosinor for all studied variables in stone formers and healthy subjects. By comparison to the healthy controls, parameter tests indicate that the stone formers had a higher MESOR (±SE) of MDA (2.90xa0±xa00.03 vs. 2.28xa0±xa00.06; Fxa0=xa094.929, pxa0<xa00.001), a lower MESOR of serum ascorbic acid (0.722xa0±xa00.010 vs. 0.839xa0±xa00.10; Fxa0=xa032.083, pxa0<xa00.001), and a similar MESOR of serum uric acid. Furthermore, the patients also differed from the healthy subjects in terms of their circadian amplitude and acrophase (tested jointly) of all three variables (pxa0<xa00.001). The demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid suggests that these variables could also serve as markers to optimize the timing of treatment and to assess the patient’s response to treatment for further management.n

Leukocyte superoxide dismutase activity in patients with chronic myeloid leukemia

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder of the hematopoieticcell and is associated with a characteristic chromosomal translocation called the Philadelphia chromosome. Clinically, CML is often divided into three phases; CML typically begins in the chronic phase (CML-CP) and in the absence of intervention and over the course of several years progresses to an accelerated phase (CML-AP) and ultimately to blast crisis. Blast crisis is the terminal phase of CML and clinically behaves like acute leukemia(1). Free radicals can be key contributory agents in a number of human diseases, including cancer and leukaemia(2,3). These free radicals can be generated within the cell not only by external sources of radiation but also within the body as a by-product of normal metabolic processes which include the electron transport chain, drugs, pollutants, and chemicals including toxins, collectively termed as xenobiotics. Thus, antioxidants which balance the oxidative stress state represent a major line of defense in regulating the overall true state of health(2). Antioxidant enzymes such as superoxide dismutase (SOD) can directly counter the oxidants and may protect cells against oxidative stress. Studies show that cancer cells have abnormal activities of SOD enzymes when compared to an appropriate normal counterpart. There are no available publications regarding the relationship between leukocyte SOD enzyme activity in CML and its progression. The present study was planned to propose leukocyte SOD activity as a possible biomarker for oxidative stress in CML and its correlation with the progressive phases of CML.