Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of primary cultures of rat hepatocytes with K2CR2O7 and deferoxamine (DFO), an iron chelator, resulted in a marked decrease in cellular levels of DNA single-strand breaks caused by K2Cr2O7. Cellular treatment with DFO also suppressed both dichromate-induced cytotoxicity--evaluated by the leakage of lactate dehydrogenase, and lipid peroxidation--as monitored by malondialdehyde formation. In addition, treatment with DFO attenuated the suppression of the levels of vitamin E and C as well as the inhibition of alkaline phosphatase and glutathione peroxidase activity attributed to K2Cr2O7. However, DFO had no influence on the cellular level of glutathione or the activity of glutathione reductase and superoxide dismutase suppressed by dichromate. Under the same experimental conditions, cellular uptake and distribution of chromium were not affected by DFO. These results indicate that DFO protects cells from chromium (VI)-induced DNA strand breaks, cytotoxicity, lipid peroxidation, vitamin E and C depression, and glutathione peroxidase inhibition The role of antioxidants in chromium (VI)-induced cytotoxicity, DNA breaks, and lipid peroxidation is discussed.
 ...
PMID:Protective effect of deferoxamine on chromium (VI)-induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes. 919 15

Pneumotoxic effects of the tri-n-butyl phosphate (TBP) are investigated on rats using biological markers in bronchoalveolar lavage fluid (BALF) and studying key antioxidant enzymes in lung homogenate. Each animal from the experimental group received intratracheally 5 microliters TBP (20% v/v in n-dodecane). Six rats from the control and treated groups are sacrificed on post-treatment days 1, 3, 7, 14, and 28. The lactate dehydrogenase activity, the total protein content and the total cell number in BALF are increased mainly on day 1 after the treatment. The activities of superoxide dismutase and catalase are decreased to day 7 and those of glutathione peroxidase and glutathione reductase on day 1 only. The malondialdehyde content is elevated to day 14. It is concluded that TBP causes moderate toxic injury of the lung parenchyma. The depression of the key antioxidant enzymes and the elevated lipid peroxidation are probably important mechanisms of the lung damage.
 ...
PMID:Antioxidant defense mechanisms in the lung toxicity of tri-n-butyl phosphate. 940 24

Of all the clinical disciplines, radiotherapy probably has the most secure and scientific foundations. In oral cancer, radiotherapy may be used as the sole treatment or in combination with other modalities of treatment. Blood samples were collected from stage III oral cancer patients attending the Oncology Department, Bernard Institute of Radiation and Oncology, Chennai Medical College, Chennai, India, before initiating radiotherapy and after the sixth week of radiotherapy. The effect of radiation on oral cancer patients has been studied using activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) and levels of malondialdehyde (MDA). The levels of MDA showed a significant increase in untreated and radiation oral cancer patients when compared with normal subjects. The activities of red blood cell (RBC) hemolysate antioxidant enzymes such as SOD, catalase, GPX, GR, GST and G6PDH showed a significant decrease, representing the lack of antioxidant defense. Radiation induces lipid peroxidation by inactivating the antioxidant enzymes, thereby rendering the system inefficient in management of the free radical attack. Thus, the degree of radiation affects the extent of the depression of the antioxidant enzyme activities and increases lipid peroxidation.
 ...
PMID:Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. 1062 47

Sediment ingestion has recently been identified as an important exposure route for toxicants in waterfowl. The effects of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho on posthatching development of Canada geese (Branta canadensis) were examined for 6 wk. Day-old goslings received either untreated control diet, clean sediment (48%) supplemented control diet, or CDARB sediment (3449 microg/g lead) supplemented diets at 12%, 24%, or 48%. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 0.68 ppm (ww), with over 90% depression of red blood cell ALAD activity and over fourfold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 1.61 ppm with decreased hematocrit, hemoglobin, and plasma protein in addition to the effects just described. The 48% CDARB diet resulted in blood lead of 2.52 ppm with 22% mortality, decreased growth, and elevated plasma lactate dehydrogenase-L (LDH-L) activity. In this group the liver lead concentration was 6.57 ppm (ww), with twofold increases in hepatic lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and in reduced glutathione concentration; associated effects included elevated glutathione reductase activity but lower protein-bound thiols concentration and glucose-6-phosphate dehydrogenase (G-6-PDH) activity. The kidney lead concentration in this group was 14.93 ppm with subacute renal tubular nephrosis in one of the surviving goslings. Three other geese in this treatment group exhibited calcified areas of marrow, and one of these displayed severe chronic fibrosing pancreatitis. Lead from CDARB sediment accumulated less readily in gosling blood and tissues than reported in ducklings but at given concentrations was generally more toxic to goslings. Many of these effects were similar to those reported in wild geese and mallards within the Coeur d'Alene River Basin.
 ...
PMID:Developmental toxicity of lead-contaminated sediment in Canada geese (Branta canadensis). 1070 32

The aim of this work was to evaluate the effect of a cycle of estivation and awakening on free radical metabolism in selected organs of the land snail Helix aspersa. Estivation for 20 days induced a 4.9- and 1.8-fold increase in selenium-dependent glutathione peroxidase activity (Se-GPX) and in total glutathione levels (GSH-eq), respectively, in hepatopancreas when compared to activity in active animals 24 h after awakening. Foot muscle Se-GPX activity was also increased 3.9-fold during estivation, whereas GSH-eq did not vary. The activities of other antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase and glutathione S-transferase) and glucose 6-phosphate dehydrogenase were unchanged in both organs. After 15 min of awakening, the glutathione disulphide (GSSG)/GSH-eq ratio increased significantly by 55% in hepatopancreas, slowly returning to the levels observed during estivation. The higher GSSG/GSH-eq ratio may be caused by increased formation of reactive oxygen species (ROS) during awakening. The levels of thiobarbituric acid reactive substances (TBARS) decreased from 49 to 30.7 nmol g(-1) wet mass in hepatopancreas after 5 min arousal and, after 30 min, TBARS rose significantly to 39.6 nmol g(-1) wet mass, gradually declining thereafter. The levels of lipid hydroperoxides in hepatopancreas and of carbonyl protein in foot muscle both decreased during awakening. The higher levels of products of free radical damage during estivation may have resulted from low levels of ROS formation associated with decreased rates of lipid hydroperoxide detoxification and oxidized protein turnover caused by metabolic depression. The regulation of the antioxidant system during hypometabolism may constitute a mechanism to minimize oxidative stress during cycles of estivation and awakening.
 ...
PMID:Hypometabolism, antioxidant defenses and free radical metabolism in the pulmonate land snail Helix aspersa. 1251 85

Many individuals with cardiovascular diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP) and alterations in nitric oxide (NO), glutathione (GSH), antioxidant enzyme activities and lipid peroxidation in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) training + nitroglycerin for 8 weeks. BP, heart rate (HR) and respiratory exchange ratio (RER) were monitored weekly for 8 weeks using tail-cuff method and oxygen/carbon dioxide analyzer, respectively. The animals were sacrificed 24 h after last treatments and plasma isolated and analyzed using HPLC, ELISA and UV-VIS spectrophotometric techniques. The results show that exercise conditioning significantly enhanced NO production (p < 0.001), GSH levels (p < 0.001), GSH/GSSG ratio (p < 0.05) and the up-regulation of the activities of catalase (CAT) (p < 0.05), glutathione peroxidase (GSH-Px) (p < 0.001), and glutathione reductase (GR) (p < 0.05), and depression of lactate levels (p < 0.001) in the plasma of the rat. These biochemical changes were accompanied by a significant increase in RER (p < 0.001) without a significant change in BP and HR. Chronic nitroglycerin administration significantly increased NO levels (p < 0.05), GSH levels (p < 0.001), superoxide dismutase (SOD) activity (p < 0.05), GST activity (p < 0.05), and decreased MDA levels (p < 0.05). These biochemical changes were accompanied by a significant decrease in BP (p < 0.05) and without any significant changes in HR and RER. Interaction of exercise training and chronic nitroglycerin treatment resulted in normalization of plasma NO, MDA, lactate levels, and CAT activity. The combination of exercise and nitroglycerin significantly enhanced GSH levels (p < 0.05), and the up-regulation of SOD (p < 0.001), GSH-Px (p < 0.05), GR (p < 0.05) and GST (p < 0.001) activities. These biochemical changes were accompanied by normalization of BP and a significant increased in RER (p < 0.001). The data suggest that the interaction of physical training and chronic nitroglycerin treatment resulted in the maintenance of BP and the up-regulation of plasma antioxidant enzyme activities and GSH levels in the rat.
 ...
PMID:Interaction of physical training and chronic nitroglycerin treatment on blood pressure and plasma oxidant/antioxidant systems in rats. 1284 29

Many individuals with cardiovascular diseases undergo periodic exercise conditioning with or without medication. Therefore, the purpose of this study was to examine the effect of exercise training on BP and HR under the condition of NOS inhibition and to clarify the mechanism of the effect in regard to oxidative stress, antioxidant enzyme activity, and NO production in the plasma of the rat. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitro-L-arginine methyl ester (L-NAME) (10mg/kg, s.c. for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) and heart rate (HR) were monitored weekly for 8 weeks. The animals were sacrificed 24h after last treatments, plasma isolated and analyzed. The results show that exercise conditioning resulted in enhanced NO production (120% of control), GSH levels (110% of control), GSH/GSSG ratio (124% of control) and the up-regulation of catalase (CAT) (225% of control), glutathione peroxidase (GSH-Px) (161% of control), glutathione reductase (GR) (142% of control) and glutathione-S-transferase (GST) (189% of control) and depression of malondialdehyde (MDA) (90% of control) and lactate (75% of control) in plasma of the rat. These biochemical changes were accompanied by no significant change in BP but slight increase in HR. Chronic L-NAME administration resulted in depression of NO (84% of control), GSH (90% of control), GSH/GSSG ratio (76% of control), the down-regulation of superoxide dismutase (SOD) (67% of control), GST (74% of control), and GR (90% of control). Plasma CAT and GSH-Px activities, MDA and lactate levels were significantly increased in L-NAME treated rats. The biochemical changes were accompanied by increase in blood pressure and heart rate. Interaction of exercise training and chronic NOS inhibitor treatment resulted in normalization of plasma NO levels, GSH/GSSG ratio, SOD and GST activities, and the up-regulation of, CAT, GSH-Px, and GR activities. The interaction resulted in depletion of plasma MDA levels compared to L-NAME treated group. The biochemical changes were accompanied by decrease in BP and HR compared to L-NAME treated group. The data suggest that the exercise training attenuated the oxidative injury caused by NOS inhibitor by increasing the plasma NO levels, GSH/GSSG ratio and up-regulating the antioxidant enzyme and lowering the BP and HR in the rat.
 ...
PMID:Interaction of exercise training and chronic NOS inhibition on blood pressure, heart rate, NO and antioxidants in plasma of rats. 1464 3

Little is known about the vascular metabolic status of glutathione (GSH), which is crucial in cell antioxidant protection, in experimental conditions like high-fat diet-induced atherosclerosis. This issue was, therefore, investigated in two groups of seven rabbits fed a 0.5% cholesterol-, 5% lard- and 5% peanut oil-enriched diet for 18 and 80 days, which, respectively, raised the plasma values of total cholesterol by factors of about 12 and 37, and those of triglycerides by factors of 3 and 13; rabbits fed a standard diet for the same periods served as controls. Total GSH and the activities of the GSH level-maintaining enzymes glutathione reductase (GSSG-Red), gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT) were specifically assessed in the aortic tissue, which was also assayed for fluorescent damage products of lipid peroxidation (FDPL). Sudan red staining of the aortic intima surface was also performed in two other groups of six controls and six fat-fed rabbits. After 18 days of fat feeding, a significant decrement of aortic GSSG-Red activity, associated with gamma-GCS activation, increased GSH levels and normal gamma-GT activity, was observed; FDPL were only moderately enhanced, and atherosclerotic lesions did not occur. After 80 days of atherogenic diet, aortic GSH content was significantly decreased in concomitance with a marked depression of gamma-GT activity, while GSSG-Red and gamma-GCS activities were not significantly changed with respect to 18 days of fat feeding; FDPL underwent further considerable augmentation, and extensive Sudan red-stained atherosclerotic lesions were evident. Thus, short-term fat feeding induces gamma-GCS-dependent GSH biosynthesis of the rabbit aorta; prolonged high-fat intake and hyperlipidemic burden result instead in vascular gamma-GT dysfunction with GSH depletion, eventually favoring oxidative atherogenic effects.
 ...
PMID:Aortic glutathione metabolic status: time-dependent alterations in fat-fed rabbits. 1517 20

The effect of dehydrotarplatin (DTP), a new antineoplastic drug analogous to cisplatin, and its metabolite (Triacid) on the hepatic, renal and testicular CYP and antioxidant enzymes of male rats was investigated. The rats were treated i.p. with a single dose of DTP (25 mg kg(-1) day(-1)) or Triacid (17.5 mg kg(-1) day(-1)) and analysed 3 or 7 days post treatment. Three days after treatment, both drugs reduced body and liver weights, which partially recovered the control level after 7 days. DTP and, to a less extent, Triacid caused a depletion of plasmatic testosterone content and a down regulation in the liver of androgen dependent male specific CYP 2C11, but not of CYP 1A and 2E1, as determined by a significant decrease of 2alpha- and 16alpha-testosterone hydroxylase activities (markers for CYP 2C11) and of apoprotein immunoreactive with anti-rat CYP 2C11 antibodies. However, the activity of testicular 17alpha-progesterone hydroxylase, a key reaction in steroidogenesis, was not altered by these drugs. The DTP and Triacid administration did not cause any alteration of the plasmatic urea nitrogen and creatinine, known as markers of kidney toxicity. However, treatment with DTP, not Triacid, either 3 and 7 days post treatment, caused in the kidney microsomes a significant increase of the total CYP content, the CYP 4A-dependent (omega)- and (omega - 1)-lauric acid hydroxylase activities and apoprotein immunoreactive with anti-rat CYP 4A1. The present study also examined the enzymatic antioxidant status of kidney and liver. Neither DTP nor Triacid administration induced, with respect to control values, any alteration of hepatic and renal glutathione reductase, glutathione S-transferase, catalase, superoxide dismutase activities, hepatic GSH level and renal microsomal lipid peroxidation level. Among the antioxidant enzymes assayed, only the renal activity of glutathione peroxidase was significantly increased after DTP but not Triacid treatment. These results indicate that DTP at a dose of 25 mg/kg and Triacid cause a feminization of the CYP enzymes in male rat liver similar to that reported for cisplatin when administered at a low dose (5 mg/kg). However, unlike cisplatin, DTP and its metabolite were unable to enhance BUN and creatinine and cause any depression of CYP activities and antioxidant enzymes in the kidney, suggesting that DTP may have low or even no potential in inducing nephrotoxicity.
 ...
PMID:Effects of the anticancer dehydrotarplatin on cytochrome P450 and antioxidant enzymes in male rat tissues. 1736 83

Stress plays a potential role in the onset and exacerbation of depression. Chronic restraint stress in rats, and psychosocial stress in humans, is implicated in the pathophysiology of mood and anxiety disorders. Oxidative damage is an established outcome of restraint stress, which has been suggested to induce many damaging processes contributing to the pathology of stress-induced depression. However, the modulatory role of clinically effective antidepressants, such as fluoxetine, in attenuating oxidative stress has not been well characterized. Therefore, the current study was designed to investigate the antioxidant effects of chronic treatment with fluoxetine in animals submitted to restraint stress. The antioxidant potential of the antidepressant fluoxetine was compared with that of turmeric, used as a standard since it integrates both antioxidant and antidepressant properties. Chronic fluoxetine administration to stressed animals for 21 days prevented restraint stress-induced oxidative damage with an efficacy similar to that of turmeric, as evidenced by significant enhancement of key endogenous antioxidant defense components, comprising the free-radical scavenging enzymes, superoxide:superoxide oxidoreductase (EC 1.15.1.1), hydrogen-peroxide:hydrogen-peroxide oxidoreductase (EC 1.11.1.6), glutathione S-transferase (EC 2.5.1.18) and glutathione:NADP(+)oxidoreductase (EC 1.8.1.7), as well as non-enzymatic antioxidants, GSH, glucose and uric acid, which were severely depleted by restraint stress in animals receiving no treatment. Oxidative stress markers, (S)-lactate:NAD(+) oxidoreductase activity (EC 1.1.1.27), malondialdehyde levels (lipid peroxidation product) and protein carbonyl content were also significantly decreased following fluoxetine treatment. Both these drugs when given alone to non-stressed animals did not alter basal levels of antioxidant defense components and oxidative stress markers significantly. Our findings suggest that the therapeutic efficacy of fluoxetine may be mediated, at least partially, via reversal of oxidative damage as demonstrated by protective enhancement of antioxidant status following a stress-induced decline. In addition, this study demonstrates important implications for pharmacological interventions targeting cellular antioxidants as a promising strategy for protecting against oxidative insults in stress-induced depression.
 ...
PMID:Antioxidant potential of fluoxetine in comparison to Curcuma longa in restraint-stressed rats. 1761 Aug 75


<< Previous 1 2 3 4 5 6 7 8 Next >>