The present study reports the cytoprotective and antioxidant properties of alcoholic leaf extract of seabuckthorn (SBT) against hypoxia induced oxidative stress in C-6 glioma cells. Exposure of cells to hypoxia for 12 h resulted in a significant increase in cytotoxicity and decrease in mitochondrial transmembrane potential compared to the controls. Further an appreciable increase in nitric oxide and reactive oxygen species (ROS) production was noted which in turn was responsible for fall in intracellular antioxidant levels and GSH/GSSG ratio. There was a significant increase in DNA damage during hypoxia as revealed by comet assay. Pretreatment of cells with alcoholic leaf extract of SBT at 200 μg/ml significantly inhibited cytotoxicity, ROS production and maintained antioxidant levels similar to that of control cells. Further, the leaf extract restored the mitochondrial integrity and prevented the DNA damage induced by hypoxia. These results indicate that the leaf extract of SBT has strong antioxidant and cytoprotective activity against hypoxia induced oxidative injury. (Mol Cell Biochem 278: 9–14, 2005)

The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 μg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities.

At high altitudes, the reactive oxygen species are continuously generated as a consequence of low oxygen partial pressure (hypoxia), which causes tissue damage. The body's defence system to combat the oxidative stress (e.g., anti-oxidant enzymes, free radical scavengers such as vitamin C, vitamin E, beta-carotene, reduced glutathione and minerals such as selenium, etc.) may diminish. In the present study, the antioxidant effect of selenium (Se) in reducing the hypoxia-induced oxidative stress was evaluated by exposing male albino rats to hypoxic stress in a decompression chamber. Exposure to hypoxia resulted in an increase in malondialdehyde (MDA) levels in plasma and tissues and a concurrent decrease in blood glutathione (GSH), glutathione peroxidase (GPx), plasma protein and plasma selenium content when compared with controls. Haemoglobin concentration (Hb%), red blood corpuscles (RBC) and white blood corpuscles (WBC) count were also increased in the hypoxia-exposed group. Selenium supplementation to animals reversed the trend. There was a significant decrease (P < 0.001) in MDA and subsequent increase in plasma and tissue GSH levels. Similarly the blood and tissue GPx and plasma protein also increased significantly in the Se supplemented animals compared with control animals. The Hb%, RBC and WBC counts showed no significant difference between Se-fed and control rats. These results suggest that selenium may help in reducing the lipid peroxidation during hypoxia.

Hypoxia is known to induce oxidative stress in organisms leading to tissue injury. In the present study beta-carotene (BC) given at 10 mg/kg body weight (BW) in reducing the oxidative stress induced by hypoxia was evaluated on male albino rats. Hypoxia exposure caused an increase in malondialdehyde (MDA) levels in plasma and tissues, a concurrent decrease in blood glutathione (GSH), glutathione peroxidase (GPx), plasma protein and plasma BC content. Hemoglobin concentration, Red blood corpuscles (RBC) and White blood corpuscles (WBC) count were also increased under hypoxia. BC supplementation reversed the trend, inducing a significant decrease (P<0.05) in MDA and subsequent increase in plasma and tissue GSH levels in animals exposed to hypoxia. Blood GPx and plasma protein also increased significantly in BC supplemented animals. BC supplementation did not alter the changes in Hb concentration, RBC and WBC count. BC has potent antioxidant activities in reducing the oxidative stress induced by hypobaric hypoxia.

BACKGROUND:There is growing evidence that free radicals mediated oxidative injury due to inadequate oxygen availability is an important factor in various pathologies at high altitude. Since vitamin E is known to protect the cells from oxidative damage due to its potent antioxidant properties, the present study was carried out to explore the effect of vitamin E supplementation on various hematological and biochemical parameters in hypoxia-induced oxidative stress in albino rats.METHODS:The experiments were conducted on male albino rats by intermittently exposing them to a simulated altitude of 7,576 m (25,000 ft), daily for 6 h for 15 d at 32 +/- 2 degrees C. The control group was fed vehicle only (1% Tween 80) and the experimental group was given vitamin E (40 mg per rat x d(-1)) orally, 5 d prior to and during the period of hypoxic exposure. The variables studied include: hemoglobin, hematocrit, RBC deformability index, alpha-tocopherol level, malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), lactate dehydrogenase (LDH) and protein level in blood/plasma and various tissues.RESULTS:Significant increase in hematocrit and hemoglobin and decrease in RBC deformability index was observed on exposure to hypoxia while vitamin E supplementation maintained them at the normal level. Hypoxia led to the decrease in plasma vitamin E and blood glutathione (GSH) level and two-fold increase in the plasma malondialdehyde (MDA) level. Vitamin E supplementation, on the other hand, resulted in less of an increase in MDA and increased the GSH concentration significantly. LDH activity, which was elevated on exposure to hypoxia, was arrested on vitamin E supplementation.CONCLUSION:The results indicate that vitamin E supplementation results in preventing oxidative damage due to high altitude stress.

The study was designed to determine the cytoprotective and immunomodulatory properties of Geriforte, an indigenous herbomineral compound, using lymphocytes as a model system. The possible involvement of free radicals and the ability of Geriforte to inhibit the oxidative process induced by tert-butylhydroperoxide (tert-BHP) was also investigated. The production of free radicals (evaluated by fluorescent probe fluorescein-diacetate), level of malondialdehyde (MDA, as index of lipid peroxidation), and levels of anti-oxidants--reduced glutathione (GSH) and glutathione peroxidase (GPx) were determined. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP (100 microM) over control. Addition of tert-BHP resulted in a marked increase in free radical production and MDA level with a concomitant decrease in GSH level in lymphocytes. Geriforte supplementation reduced cytotoxicity and apoptosis induced by tert-BHP. Further, Geriforte inhibited tert-BHP induced lipid peroxidation and maintained higher anti-oxidant levels. tert-BHP significantly inhibited the lymphocyte proliferation stimulated by mitogens (Lipopolysaccharide/Concanavalin A) and enhanced DNA fragmentation. Geriforte relieved the inhibitory effect of tert-BHP on lymphocyte proliferation and decreased DNA fragmentation appreciably. The results indicate that Geriforte possesses cytoprotective and immunomodulatory properties which could be due to its anti-oxidant activity.

The effect of Kombucha tea (KT) on oxidative stress induced changes in rats subjected to chromate treatment are reported. KT feeding alone did not show any significant change in malondialdehyde (MDA) and reduced glutathione (GSH) levels, but did enhance humoral response and delayed type of hypersensitivity (DTH) response appreciably over control animals. Chromate treatment significantly enhanced plasma and tissue MDA levels, decreased DTH response considerably, enhanced glutathione peroxidase and catalase activities; however, no change in GSH, superoxide dismutase and antibody titres was noticed. KT feeding completely reversed the chromate-induced changes. These results show that Kombucha tea has potent anti-oxidant and immunopotentiating activities.

BACKGROUND:The objective of this study is to evaluate the efficacy of oral glutamic acid supplementation in promoting hypoxic tolerance.METHODS:The experiments were conducted in albino rats by exposing them to three levels of hypoxia in a simulated environment for varying periods of time. The parameters studied include: gasping time at 35,000 ft (10,668 m), food and water intake, and heart to body weight (b.w.) ratio at 25,000 ft (7620 m), tolerance to composite stress at 15,000 ft (4572 m) and biodistribution of glutamate (glu).RESULTS:Supplementation of Glu (27 mg x kg(-1) b.w.) as glutamic acid dissolved in normal saline resulted in 4.8 times enhanced hypoxic tolerance (time taken for appearance of first gasp), 23% body weight gain and 24% increase in food consumption over control during hypoxia. When animals were subjected to composite stress of cold, hypoxia and restraint (CHR), the Glu fed animals showed higher resistance to fall in rectal temperature than the control group. Hypoxia significantly enhanced heart to body weight ratio compared with control, and Glu supplementation reduced and brought it down to that of control.CONCLUSION:The study reveals that Glu in optimal doses may be a conditionally essential amino acid resulting in enhanced tolerance to hypoxia and cold.

High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32±2° C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

The immunomodulatory properties of NIM-76 have been described in this paper. Pre-treatment of rats with a single i.p. injection of NIM-76 resulted in an increase in polymorphonuclear (PMN) leukocytes with a concomitant decrease in lymphocyte counts. The immunomodulatory activity of NIM-76 was found to be concentration-dependent. At 120 mg/kg body weight, there was an enhanced macrophage activity and lymphocyte proliferation response, while the humoral component of immunity was unaffected. At higher concentrations of NIM-76 (300 mg/kg body weight), there was a stimulation of mitogen-induced lymphocyte proliferation, while macrophage activity remained unaffected. However, a fall in primary and secondary antibody titres was observed. The study indicates that NIM-76 acts through cell-mediated mechanisms by activating macrophages and lymphocytes.