Melatonin Prevents Oxidative Stress and Hepatocyte Cell Death Induced by Experimental Cholestasis

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.     

Bile duct ligation and oxidative stress in the rat: effects in liver and kidney

In the liver, seven days of bile duct ligation (BDL) decreases the cytochrome P-450 content and the UDP-glucuronyl transferase activity. Also, a decrease in the water soluble antioxidant mechanism reflected in the activities of the enzymes superoxide dismutase (SOD), catalase and the glutathione peroxidase (GTPx) was found in the liver but not in the kidney. Despite an increase in the amount of the GSH in the liver, increased lipid peroxidation is produced in the BDL rats, as indicated by the levels of malondialdehyde (MDA). The kidney responded in a different way to cholestasis, decreasing only the UDP-glucuronyl transferase activity and increasing the levels of GSH and MDA. In the red blood cells the activity of the antioxidant enzymes SOD, GTPx and catalase and the content of GSH were not modulated by cholestasis. In conclusion, disturbance of the oxidant-antioxidant balance might be responsible for cholestatic liver injury and impaired renal function in BDL rats.     

Fluoride-Induced Oxidative Stress in Rat’s Brain and Its Amelioration by Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Pineal Proteins and Melatonin

Fluoride (F) becomes toxic at higher doses and induces some adverse effects on various organs, including brain. The mechanisms underlying the neurotoxicity caused by excess fluoride still remain unknown. The aims of this study were to examine F-induced oxidative stress (OS) and role of melatonin (MEL) and buffalo pineal proteins (PP) against possible F-induced OS in brain of rats. The 24 rats were taken in present study and were divided into four groups: control, F, F + PP, and F + MEL. The F group was given 150 mg/L orally for 28 days. Combined 150 ppm F and 100 μg/kg BW (i.p.) PP and F (150 ppm) + MEL (10 mg/kg BW, i.p.) were also administered. The activities of enzymatic, viz., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), and non-enzymatic, viz., reduced glutathione (GSH) concentration, and the levels of malondialdehyde (MDA) in the brain tissue were measured to assess the OS. Fluoride administration significantly increased brain MDA compared with control group, while GSH levels were decreased in fluoride-treated groups, accompanied by the markedly reduced SOD, GPx, GR, and SOD activity. Buffalo PP and MEL administration caused brain MDA to decrease but caused SOD, GPx, GR, GSH, and CAT activities to increase to significant levels in F-treated animals. Together, our data provide direct evidence that buffalo PP and MEL may protect fluoride-induced OS in brain of rats through mechanisms involving enhancement of enzymatic and non-enzymatic antioxidant defense system. Therefore, this study suggested that PP and MEL can be useful in control of neurotoxicity induced by fluoride.     

p38-MAPK- and caspase-3-mediated superoxide-induced apoptosis of rat hepatic stellate cells: reversal by retinoic acid

Reactive oxygen species (ROS) activate retinoid-containing quiescent hepatic stellate cells (qHSCs) to retinoid-deficient fibrogenic myofibroblast-like cells (aHSCs). However, ROS also cause apoptosis of aHSCs, and apoptotic aHSCs are observed in inflammatory fibrotic liver. Here, we investigated mechanisms of the effects of oxidative stress on the survival of qHSCs and aHSCs. HSCs from normal rat liver were used after overnight culture (qHSCs), or in 3-5 passages (aHSCs). For in vivo induction of oxidative stress, tert-butylhydroperoxide was injected into control and CCl4-induced cirrhotic rats. Spontaneous caspase-3 activation and apoptosis, observed in cultured qHSCs, decreased with time and were unaffected by superoxide. In contrast, superoxide caused caspase-3 and p38-MAPK activation, reduction in Bcl-xL expression, and apoptosis in aHSCs. Inhibition of caspase-3 and p38-MAPK did not affect the viability of qHSCs in the absence or presence of superoxide, but inhibited superoxide-induced death of aHSCs. Glutathione (GSH) level and activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were lower in aHSCs than qHSCs. Superoxide increased GSH content, and activities of SOD, catalase and GPx in qHSCs but not in aHSCs. Incubation of 13-cis-retinoic acid (RA)-treated aHSCs with superoxide increased their GSH content significantly, and prevented superoxide-induced p38-MAPK and caspase-3 activation while dramatically reducing the extent of apoptosis. Finally, oxidative stress induced in vivo caused apoptosis of aHSCs in cirrhotic but not of qHSCs in control rats. These results suggest that the absence of retinoids render aHSCs susceptible to superoxide-induced apoptosis via caspase-3 and p38-MAPK activation.     

Lead-induced lipid peroxidation and antioxidant defense components of developing chick embryos.

Administration of lead (1.25 and 2.5 mumol/kg egg weight) to 14-day-old chick embryos enhanced the level of lipid peroxides (LPO) in tissues of liver, brain, and heart. Accumulation of LPO was maximum at 9 h after treatment with lead and returned to normal level by 72 h. Further, we have studied the levels of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. At 9 h posttreatment, the hepatic GR was reduced significantly with the induction of GST and considerable depletion of GSH. However, in brain and heart, both GR and GST activities were unaltered with significant reduction of GSH. Further, an increase of non-Se-dependent GPx and SOD activities were observed in liver, brain, and heart. Similarly, at 72 h, although the GPx activity was found decreased in liver and brain, the GST, catalase, and SOD activities were significantly increased in all the three tissues alike, suggesting tissue-specific changes of antioxidant defense components in response to lead treatment. Our results suggests that the elevated levels of GST, SOD, and catalase at 72 h were successful in bringing LPO levels back to normal.     

Antioxidant enzyme activities and the production of MDA and 8-oxo-dG in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a neoplastic disease susceptible to antioxidant enzyme alterations and oxidative stress. We have examined the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the oxidized/reduced glutathione (GSSG/GSH) ratio together with the levels of malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG) in lymphocytes of CLL patients and compared them with those of normal subjects of the same age. SOD and CAT activity decreased in CLL lymphocytes while GPx activity increased. GSH content of CLL lymphocytes also increased, and GSSG concentration remained constant. Thus, a reduced GSSG/GSH ratio was obtained. The oxidation product MDA, and the damaged DNA base 8-oxo-dG were also increased in CLL. The observed changes in enzyme activities, GSSG/GSH ratio, and MDA were significantly enhanced as the duration of the disease increased in years. The results support a predominant oxidative stress status in CLL lymphocytes and emphasize the role of the examined parameters as markers of the disease evolution.     

Quercetin attenuates lindane induced oxidative stress in wistar rats

A wide number of pesticides, including highly persistent organochlorine compounds, such as lindane (γ-Hexachlorocyclohexane), have deteriorative effect on fauna and flora by inducing oxidative stress. Lindane induces cell damage by producing free radicals and reactive oxygen species. Quercetin, a dietary flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. In this study the flavonoid quercetin was used to investigate its antioxidative effect against lindane induced oxidative stress in rats. The level of lipid peroxidation, reduced glutathione (GSH) were analysed in addition to the antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities in the liver and kidney tissue. Levels of hepatic marker enzymes in serum like Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and renal markers like serum creatinine and serum urea were estimated. Administration of Lindane induced histopathological alterations and increased levels of serum hepatic and renal markers and malondialdehyde (MDA) with a significant decrease in GSH content and CAT, SOD, GPx and GST activities. Cotreatment of quercetin along with lindane significantly decreased the lindane induced alteration in histology, serum hepatic and renal markers and MDA and also improved the cellular antioxidant status. The results show that Quercetin ameliorates Lindane induced oxidative stress in liver and kidney. The quercetin exhibited chemopreventive effect when administered along with lindane.     

Cytotoxic effects of 4-octylphenol on fish hepatocytes

The present study was conducted to determine cytotoxic effects of 4-octylphenol (4-OP) on primary cultured hepatocytes of pearl mullet (Alburnus tarichi). Lactate dehydrogenase (LDH) release, malondialdehyde (MDA) level, antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST)] and glutathione (GSH) content were measured after 24-h exposure to 4-OP. 4-OP caused dose- and time-dependent increases in LDH release. Significant induction of MDA level and decrease in GSH content were found. SOD and GPx activities were decreased while GST activity was increased. These findings suggest that 4-OP leads to cytotoxicity by depressing antioxidant defenses in fish hepatocytes.     

The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity

Usually, all newborns demonstrate high serum unconjugated bilirubin (UCB) level. UCB may induce adverse effects in the central nervous system. We aimed to evaluate the cytotoxic effects of UCB and the protective effects of docosahexaenoic acid (DHA) on astrocyte cell cultures. The viability of astrocyte cells decreased after UCB treatment in a dose-dependent manner. Pre-incubation of DHA prevents the cells from UCB-mediated neurotoxicity. Our results shown that UCB leads to inhibition of antioxidant enzymes superoxide dismutase (SOD), catalase and GPx activity and induction of apoptosis. But only 4-h pretreatment of DHA can suppress of UCB-mediated inhibition of antioxidant enzymes SOD, catalase and GPx activity and induction of apoptosis in astrocytes. Our results strongly indicated that DHA has a protective effect on UCB-mediated neurotoxicity through inhibition apoptosis and antioxidant enzymes activity of SOD, CAT and GPx in rat primer astrocyte cell line     

Glutathione metabolism is modulated by postmortem interval, gender difference and agonal state in postmortem human brains

The equilibrium between antioxidant function and oxidative stress is implicated in brain pathology. However, human studies on oxidant and antioxidant markers rely on postmortem tissue that might be affected by pre and postmortem factors. To evaluate the effect of these variables, we tested whether antioxidant enzymes [superoxide dismutase (SOD), catalase] glutathione (GSH) and related enzymes [gamma glutamylcysteine ligase (GCL), GSH peroxidase (GPx), GSH reductase (GR), GSH-S-transferase (GST)] and malondialdehyde (MDA, marker of lipid peroxidation) are affected in postmortem human brains (n = 50) by increase in postmortem interval (2.5–26 h), gender difference and agonal state [based on Glasgow coma scale (GCS): range: 3–15] in different anatomical regions-frontal cortex (FC), cerebellum (CB) medulla oblongata (MO), substantia nigra (SN) and hippocampus (HC). While SOD and catalase activities were relatively unaltered, GR and GPx activities were affected by agonal state (GR in CB, p < 0.05; GPx in MO, p < 0.05) indicating altered GSH dynamics during the secondary events following neuronal injury. MO, SN and HC displayed low GSH compared to FC and CB. Total GSH level was decreased with PMI (MO, p = 0.02) which could be partly attributed to increase in MDA levels with increasing PMI in MO (p < 0.05). Total GSH level was higher in CB (p < 0.017) and MO (p < 0.04) in female brains compared to males. Interestingly, HC and SN regions showed significant stability in most of the markers tested. We suggest that while SOD and catalase were relatively unaffected by the pre and postmortem factors, GSH and its metabolic enzymes were significantly altered and this was more pronounced in MO of postmortem human brains. These data highlight the influence of pre and postmortem factors on GSH dynamics and the inherent differences in brain regions, with implications for studies on brain pathophysiology employing human samples.     

Can we reduce oxidative stress with liver transplantation?

BackgroundThe aim of this study was to determine the levels of lipid peroxidation (MDA) and antioxidants such as reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the blood serum of patients with cirrhosis and liver transplantation.MethodsIn this study, serum malondialdehyde acid (MDA) levels, superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) activities were measured spectrophotometrically and compared to the results of the healthy control group.ResultsSOD, CAT and GSH activities were significantly decreased in the patient groups compared to the healthy control group (p<0.05). MDA levels were significantly higher in the patient group compared to the healthy control group (p <0.05).ConclusionsIn conclusion, this study demonstrated that oxidative stress may play an important role in the development of liver cirrhosis and in liver transplantation. This study is the first one to show how MDA, SOD, CAT and GSH levels change in liver cirrhosis and liver transplantation, while further studies are essential to investigate antioxidant enzymes and oxidative stress status in patients with cirrhosis and liver transplantation.     

Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia

In this article, oxidative stress and enzymic-non-enzymic antioxidants status were investigated in children with acute pneumonia. Our study included 28 children with acute pneumonia and 29 control subjects. The age ranged from 2 to 11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There was a statistically significant difference between the groups for all parameters except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were higher in the study group than those of the control group. However, SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the study group compared with the control group. All antioxidant vitamin activities were decreased in children with acute pneumonia. Our study demonstrated that oxidative stress was increased whereas enzymic and non-enzymic antioxidant activities were significantly decreased in children with acute pneumonia.     

Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats

Nasturtium officinale R. Br. (Brassicaceae) has been used as a home remedy by the people of south eastern (SE) region of Iran as a medicinal plant. This therapeutical application has been attributed to Nasturtium officinale (N. officinale) antioxidant capacity which is mostly tested by means of cell-free assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). In addition, the antioxidant effect of N. officinale extract has been investigated in hypercholesterolaemic rats in vivo. The results revealed that the extract has notable scavenging activity against DPPH radicals as well as potent reducing power in FRAP assay. Intragastric administration of N. officinale (500 mg/kg body weight per day) to groups of hypercholesterolaemic rats for 30 days lowered their blood total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively. However, the blood high density lipoprotein cholesterol (HDL-C) levels in the same treated rats increased by 16%. To evaluate the mechanism(s) of action, we studied the antioxidative potential of N. officinale extract in terms of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and also the level of reduced glutathione (GSH) in the liver tissues. In addition, hepatic tissue malondialdehyde level (MDA, an index of lipid peroxidation) was also determined. Under hypercholesterolaemic condition, hepatic MDA was increased. Moreover, our data indicated GSH depletion along with significant reduction in the activities of CAT and SOD in rats fed high-fat diet rats. On the other hand, significant elevation in the activities of GPx and GR were seen in the same group of rats. Treatment of hypercholesterolaemic rats with N. officinale extract significantly increased the GSH level along with enhanced CAT and SOD activities in liver tissues. Furthermore, N. officinale extract significantly decreased hepatic MDA as well as GPx and GR activities in plant-treated rats. Based on our data, it can be concluded that N. officinale has a high hypolipidaemic activity and this may be attributed to its antioxidative potential.     

Activation of superoxide dismutase in selenium-deficient mice infected with influenza virus.

Selenium (Se) deficiency is associated with decreased activities of Se-dependent antioxidant enzymes, glutathione peroxidase (GPx) and thioredoxin reductase (TR), and with changes in the cellular redox status. We have previously shown that host Se deficiency is responsible for increased virulence of influenza virus in mice due to changes in the viral genome. The present study examines the antioxidant defense systems in the lung and liver of Se-deficient and Se-adequate mice infected with influenza A/Bangkok/1/79. Results show that neither Se status nor infection changed glutathione (GSH) concentration in the lung. Hepatic GSH concentration was lower in Se-deficient mice, but increased significantly day 5 post infection. No significant differences due to Se status or influenza infection were found in catalase activities. As expected, Se deficiency was associated with significant decreases in GPx and TR activities in both lung and liver. GPx activity increased in the lungs and decreased in the liver of Se-adequate mice in response to infection. Both Se deficiency and influenza infection had profound effects on the activity of superoxide dismutase (SOD). The hepatic SOD activity was higher in Se-deficient than Se-adequate mice before infection. However, following influenza infection, hepatic SOD activity in Se-adequate mice gradually increased. Influenza infection was associated with a significant increase of SOD activity in the lungs of Se-deficient, but not Se-adequate mice. The maximum of SOD activity coincided with the peak of pathogenesis in infected lungs. These data suggest that SOD activation in the lung and liver may be a part of a compensatory response to Se deficiency and/or influenza infection. However, SOD activation that leads to increased production of H(2)O(2) may also contribute to pathogenesis and to influenza virus mutation in lungs of Se-deficient mice.     

Inhibition of c-Jun expression induces antioxidant enzymes under serum deprivation

We previously reported that antisense c-jun suppressed apoptosis induced by serum deprivation in F-MEL cells. To elucidate the molecular mechanisms responsible for this suppression of apoptosis we investigated the activities and protein expression of antioxidant materials in the cell under serum deprivation. In the parental F-MEL cells enzyme activities of catalase, glutathione S-transferase (GST), and glutathione peroxidase (GPx) increased to reach the maximum at 24-72 h after removal of serum and then decreased to initial levels or a little less. Superoxide dismutase (SOD) maintained the initial level for 72 h and increased 1.5- to 2-fold at 96 h. Glutathione (GSH) levels increased at 24 h and then dropped significantly to one-third the initial level. On the other hand, in c-junAS (+) cells, in which antisense c-jun was expressed and c-Jun protein expression was reduced to undetectable level. We found 1.9-, 2.7-, 4.8-, and 15. 8-fold increase in the activities of catalase, GST, SOD, and GPx, respectively, at 96 h. GSH maintained almost the same level as the initial. Enhancement of these enzyme activities in c-junAS (+) cells was induced under serum deprivation. Western blottings for catalase, GST, and SOD also showed enhanced increase in protein expression, supporting the increase in enzyme activities. Cellular peroxide level under serum deprivation was monitored by flow cytometry using DCFH-DA as a probe. We found that the peroxide level increased at 24 h and then decreased at 72 and 96 h in c-junAS (+) cells, and reduction of the peroxide level coincided with an increase in antioxidant enzyme activities. These results indicate that antioxidant materials such as catalase, GST, SOD, GPx, and GSH are induced by serum deprivation when c-jun expression is inhibited in F-MEL cells. The link between inhibition of c-jun expression and enhancement of cellular antioxidant defense is discussed.     

The potential effects of antioxidant feed additives in mitigating the adverse effects of corn naturally contaminated with <Emphasis Type="Italic">Fusarium</Emphasis> mycotoxins on antioxidant systems in the intestinal mucosa,plasma, and liver in weaned pigs

Seventy-two piglets (6.0 kg BW) were randomly distributed within six different dietary treatments to evaluate the effect of deoxynivalenol (DON) and the potential of four antioxidant feed additives in mitigating the adverse effects of DON on growth performances and oxidative status. Dietary treatments were as follows: control diet 0.8 mg/kg DON; contaminated diet (DON-contaminated diet) 3.1 mg/kg DON; and four contaminated diets, each supplemented with a different antioxidant feed additive, DON + vitamins, DON + organic selenium (Se)/glutathione (GSH), DON + quercetin, and DON + COMB (vitamins + Se/GSH + quercetin from the other treatments). Although DON was the main mycotoxin in the contaminated diet, this diet also contained 1.8 mg/kg of zearalenone (ZEN). The “mycotoxin” effects therefore included the combined effect of these two mycotoxins, DON, and ZEN. The DON-ZEN ingestion did not affect growth performances, average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F ratio), but partially induced oxidative stress in weaned pigs as shown by increased malondialdehyde (MDA) content in the plasma and superoxide dismutase (SOD) activity in liver (P?<?0.05). However, no change in the activity of other antioxidant enzymes or GSH concentrations was observed in plasma and liver of piglets fed the DON-contaminated diet (P?>?0.05). Supplementation with individual antioxidant feed additive had a limited effect in weaned pigs fed DON-ZEN-contaminated diets. Combination of antioxidants (vitamins A, C, and E, quercetin, and organic Se/GSH) reduced plasma and liver MDA content and SOD activity in liver (P?<?0.05) of piglets fed DON-ZEN-contaminated diets. Furthermore, this combination also reduced MDA content in the ileum (P?<?0.05), although activity of glutathione peroxidases (GPx), SOD or catalase (CAT) in the ileum was not affected by DON-ZEN contamination or antioxidant supplements. In conclusion, DON-ZEN contamination induced oxidative stress in weaned pigs and combination of antioxidant feed additives restored partially the oxidative status. Further studies will be necessary to assess whether the effects of antioxidant feed additives on oxidative status are specific when feed is contaminated with DON-ZEN.     

Tinospora cordifolia induces enzymes of carcinogen/drug metabolism and antioxidant system, and inhibits lipid peroxidation in mice

The present study is an effort to identify a potent chemopreventive agent against various diseases (including cancer) in which oxidative stress plays an important causative role. Here, we investigated the effect of a hydroalcoholic (80% ethanol: 20% distilled water) extract of aerial roots of Tinospora cordifolia (50 and 100mg/kg body wt./day for 2 weeks) on carcinogen/drug metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione (GSH) content, lactate dehydrogenase and lipid peroxidation in liver of 8-week-old Swiss albino mice. The modulatory effect of the extract was also examined on extrahepatic organs, i.e., lung, kidney and forestomach, for the activities of GSH S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD) and catalase. Significant increases in the levels of acid-soluble sulfhydryl (-SH) and cytochrome P(450) contents, and enzyme activities of cytochrome P(450) reductase, cytochrome b(5) reductase, GST, DTD, SOD, catalase, GSH peroxidase (GPX) and GSH reductase (GR) were observed in the liver. Both treated groups showed decreased malondialdehyde (MDA) formation. In lung SOD, catalase and GST; in kidney SOD and catalase; and in forestomach SOD, DTD and GST showed significant increase at both dose levels of treatment. BHA (0.75%, w/w in diet), a pure antioxidant compound, was used as a positive control. This group showed increase in hepatic levels of GSH content, cytochrome b(5), DTD, GST, GR and catalase, whereas MDA formation was inhibited significantly. In the BHA-treated group, the lung and kidney showed increased levels of catalase, DTD and GST, whereas SOD was significantly increased in the kidney and forestomach; the latter also showed an increase in the activities of DTD and GST. The enhanced GSH level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of T. cordifolia against chemotoxicity, including carcinogenicity, which warrants further investigation of active principle (s) present in the extract responsible for the observed effects employing various carcinogenesis models.     

Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer