Can Cranberry Juice Protect against Rotenone-Induced Toxicity in Rats?

The high polyphenols content of cranberry accounts for its strong antioxidant activity underlying the beneficial health effects of this fruit. Rotenone (ROT) is a specific inhibitor of mitochondrial complex I in the brain which leads to the generation of oxidative stress. To date, there are few data indicating that toxicity of ROT is not limited to the brain but can also affect other tissues. We aimed to examine whether ROT-induced oxidative stress could be counteracted by cranberry juice not only in the brain but also in the liver and kidney. Wistar rats were given the combined treatment with ROT and cranberry juice (CJ) for 35 days. Parameters of antioxidant status were determined in the organs. ROT enhanced lipid peroxidation solely in the brain. The increase in the DNA damage was noticed in all organs examined and in leukocytes. The beneficial effect of CJ on these parameters appeared only in the brain. Additionally, CJ decreased the activity of serum hepatic enzymes. The effect of CJ on antioxidant enzymes was not consistent, however, in some organs, CJ reversed changes evoked by ROT. Summing up, ROT can cause oxidative damage not only in the brain but also in other organs. CJ demonstrated a protective effect against ROT-induced toxicity.

Effect of Chokeberry Juice on N-Nitrosodiethylamine-Induced Rat Liver Carcinogenesis.

Because humans commonly consume chokeberry, especially as a nutritional supplement, it must be checked to determine whether its excessive ingestion can cause adverse effects, in particular, in the case of simultaneous exposure to some xenobiotics. From this point of view, we examined the impact of long-term cotreatment of rats with chokeberry juice and hepatic carcinogen N-nitrosodiethylamine (NDEA) on oxidative damages and neoplastic lesions in the liver of rats. Daily exposure to chokeberry juice in a concentration of 10 g/kg feed via diet for 13 wk led to an intensified hepatotoxic effect of NDEA (0.01% in drinking water for 13 wk), as evidenced by changes in histopathological architecture of liver tissue, increased lipid peroxidation, protein carbonyl formation, and DNA degradation. Moreover, we noticed an increase in relative liver weight and a decrease in body weight in this group in comparison to NDEA-alone treated animals. Chokeberry juice applied alone did not cause any adverse effects in rats. On the basis of these findings, it can be concluded that high doses and longterm administration of chokeberry juice may enhance tumor-promoting action of some chemical carcinogens.

Protective Effect of Morus alba Leaf Extract on N-Nitrosodiethylamine-induced Hepatocarcinogenesis in Rats.

BACKGROUND/AIM: The leaves of white mulberry (Morus alba L.) contain various polyphenolic compounds possessing strong antioxidant activity and anticancer potential. This study was designed to investigate the chemopreventive effect of aqueous extract of mulberry leaves against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis. MATERIALS AND METHODS: Wistar rats were divided into four groups: control, mulberry extract-treated, NDEA-treated, and mulberry extract plus NDEA-treated. Mulberry extract was given in the diet (1,000 mg/kg b.w./day); NDEA was given in drinking water. RESULTS: Mulberry extract reduced the incidence of hepatocellular carcinoma, dysplastic nodules, lipid peroxidation, protein carbonyl formation, and DNA degradation. Treatment with mulberry leaf extract along with NDEA challenge did not affect the activity of antioxidant enzymes and glutathione content. CONCLUSION: Treatment with mulberry leaf extract partially protected the livers of rats from NDEA-induced hepatocarcinogenesis and a direct antioxidant mechanism appears to contribute to its anticarcinogenic activity.

Evaluation of Safety and Antioxidant Activity of Yellow Tea (Camellia sinensis) Extract for Application in Food.

The article presents an evaluation of the safety of yellow tea (Camellia sinensis) extract consumption and its antioxidant activity in an animal model. Wistar rats were exposed through diet to 2, 6, and 10 g yellow tea extract/kg feed for 90 days. No signs of toxicity and no differences in mean body weight gain in the treated and control rats were recorded throughout the experiment. No statistically significant differences in hematology findings and clinical chemistry parameters were observed between controls and treated groups. Microscopic examination of tissue sections revealed no pathology attributable to yellow tea extract intake. Lipid peroxidation level in the liver was slightly increased in medium-dose males and high-dose females and decreased in two female groups receiving 2 and 6 g/kg of the extract tested. Content of carbonyl groups in protein, as well as the basal level of DNA damage, was not changed. In a majority of rats, the activity of antioxidant enzymes was increased except superoxide dismutase in high-dose groups, glutathione peroxidase in high-dose females, glutathione reductase in low- and mid-dose groups, and glutathione S-transferase in mid-dose females and high-dose males. It could be concluded that rats tolerated well dietary treatment with yellow tea extract up to 0.8 g/kg b.w./day for 90 days. Results showed that yellow tea extract at the doses tested did not demonstrate adverse effects and improved the antioxidant status in the liver of rats.

Protective effect of yellow tea extract on N-nitrosodiethylamine-induced liver carcinogenesis.

Context Yellow tea containing the same catechins as other types of tea but in different proportions has been suggested to possess potent anticancer activities. Objective This study investigates the chemopreventive effect of yellow tea aqueous extract against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis in rats by employing histological and biochemical methods. Materials and methods Wistar rats were divided randomly into four groups: control (I), yellow tea (II), NDEA (III), and yellow tea + NDEA (IV). Groups II and IV were exposed via a diet to yellow tea extract in a concentration of 10 g/kg feed; groups III and IV received 0.01% NDEA in drinking water. The experiment lasted for 13 weeks. Results Daily intake of yellow tea in an average dose of 800 mg/kg b.w. alleviated the carcinogenic effect of NDEA as evidenced by reversed histopathological changes towards normal hepatocellular architecture and decreased lipid peroxidation, protein carbonyl formation, and DNA degradation by 64%, 37% and 15%, respectively, as compared with values obtained in NDEA alone-treated rats. Treatment with yellow tea extract caused protection of superoxide dismutase (SOD) and catalase (CAT); their activity was recovered by 47% and 12%, respectively, as compared with the NDEA-treated rats. Moreover, the extract normalized the NDEA-induced activity of paraoxonase 1 (PON1) and glutathione peroxidase (GPx), while a further increase in the level of reduced glutathione (GSH) was noticed. Conclusions On the basis of these findings, it can be concluded that treatment with yellow tea partially protected the livers of rats from NDEA-induced hepatocarcinogenesis and that its antioxidant activity contributed to this effect.

Evaluation of Safety of Iron-Fortified Soybean Sprouts, a Potential Component of Functional Food, in Rat.

Ferritin-iron is currently considered as one of the most promising iron forms to prevent iron deficiency anaemia. We found that the cultivation of soybean seeds in a solution of ferrous sulfate results in material with extremely high iron content - 560.6 mg Fe/100 g of dry matter, while ferritin iron content was 420.5 mg/100 g dry matter. To assess the potential adverse effects of a preparation containing such a high concentration of iron, male and female Wistar rats were exposed via diet to 10, 30, 60 g soybean sprouts powder/kg feed for 90 days. There were no differences in final body weight and mean food consumption between controls and rats administered sprouts. No statistically significant differences in haematology and clinical chemistry parameters were found between controls and treated rats. Microscopic examination of 22 tissues did not reveal any pathology due to soybean sprouts intake. Long term administration of the test material did not cause oxidative damage to DNA and protein in the liver as evidenced by the unchanged basal levels of DNA damage as well as carbonyl groups content. Lipid peroxidation was slightly increased only in females. The activity of several antioxidant enzymes: superoxide dismutase, glutathione peroxidase and glutathione S-transferase was increased, which substantially enhanced the antioxidant status in the liver from the rats treated with soybean sprouts. Hence, the material tested can be recommended as a component of food supplements for individuals with iron deficiency anaemia and inflammatory bowel diseases.

INFLUENCE OF CLOUDY APPLE JUICE ON N-NITROSODIETHYLAMINE- INDUCED LIVER INJURY AND PHASES I AND II BIOTRANSFORMATION ENZYMES IN RAT LIVER.

Cloudy apple juice (CAJ) is a rich source of nutrients as well as non-nutrient components including high quantity of polyphenols, particularly oligomeric procyanidins, which are considered as potential chemopreventive agents that protect against the action of chemical carcinogens. The aim of this study was to examine the effect of CAJ alone or in combination with hepatocarcinogenic N-nitrosodiethylamine (NDEA) on liver damage biomarkers, including DNA damage, and the phase I and II enzymes in rat. The forced feeding with CAJ alone for 28 days, has slightly reduced the activities of phase I enzymes, MROD (CYP1A2 biomarker) and PNPH (CYP2El biomarker), while phase II enzymes, glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase-1 (NQO1), were elevated. Combined treatment of rats with CAJ and NDEA significantly reduced the levels of hepatic ALT and SDH (by ~100%) as compared to values from NDEA-treated animals. CAJ pretreatment further increased the PROD (CYP2B biomarker) and NQO1 activities increased by NDEA administration. Modulation of enzymes activities was accompanied by the changes in the proteins levels. These results indicate that CAJ may protect liver against damage induced by NDEA. Moreover, a significant decrease of SDH activity by CAJ may confirm its potential anti-diabetic activity.

Effect of tannic acid, resveratrol and its derivatives, on oxidative damage and apoptosis in human neutrophils.

In this study we compared the antioxidant and DNA protective activity of tannic acid and stilbene derivatives, resveratrol, 3,5,4(')-trimethoxystilbene (TMS) and pterostilbene in human neutrophils stimulated to oxidative burst by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in relation to apoptosis induction. All polyphenols within the concentration range 1-100 µM reduced the intracellular ROS and H2O2 production in the TPA-stimulated cells. Tannic acid was the most effective polyphenol in protection against DNA damage induced by TPA. In the resting neutrophils resveratrol and to lesser extent other polyphenols increased DNA damage and increased the level of p53. Pretreatment of the TPA-stimulated cells with tannic acid or stilbenes led to the induction of apoptosis. The most significant effect was observed as a result of treatment with TMS and resveratrol. These compounds appeared the most effective inducers of p53 in the TPA-challenged neutrophils, what may suggest that pro-apoptotic activity of these stilbenes might be related to p53 activation. Overall, the results of our present study demonstrate that tannic acid and stilbenes modulate the ROS production, ultimately leading to cell apoptosis in human neutrophils stimulated to oxidative burst. In resting neutrophils they exhibit pro-oxidant activity, which is accompanied by p53 induction.

Antioxidant effect of lycopene-enriched tomato paste on N-nitrosodiethylamine-induced oxidative stress in rats

Lycopene is a carotenoid pigment produced by vegetables and fruits, with tomatoes and their processed products being the most abundant sources. A high number of conjugated dienes make lycopene a powerful radical scavenger. Its antioxidant properties are considered to be primarily involved in many beneficial health effects. The present study was designed to assess the protective effect of lycopene-enriched tomato paste against N-nitrosodiethylamine (NDEA)-induced oxidative stress in rats. Forty-eight male Wistar rats were divided randomly into six groups. Four groups were treated with tomato paste, per os, for 28 days in doses which were equivalent to 0.5 (groups II and V) and 2.5 mg/kg b.w./day of lycopene (groups III and VI). Rats from groups IV-VI were given intraperitoneally a single dose of NDEA, 150 mg/kg b.w. Group I (control) was given distilled water. Pretreatment with tomato paste protected the antioxidant enzymes: superoxide dismutase, catalase and glutathione reductase. Their activity was recovered by 32-97 %, as compared to NDEA-treated rats. Microsomal lipid peroxidation in the liver was decreased in rats pretreated with a lower dose of tomato paste by 28 %, as compared to animals given NDEA alone. Pretreatment with tomato paste caused a decrease in plasma concentration of protein carbonyls, even below the control level, in rats given NDEA. Moreover, a 10 % reduction of DNA damage in leucocytes caused by NDEA was observed. The tomato paste tested was able to suppress NDEA-induced oxidative stress in rats

Antioxidant effect of lycopene-enriched tomato paste on N-nitrosodiethylamine-induced oxidative stress in rats.

Lycopene is a carotenoid pigment produced by vegetables and fruits, with tomatoes and their processed products being the most abundant sources. A high number of conjugated dienes make lycopene a powerful radical scavenger. Its antioxidant properties are considered to be primarily involved in many beneficial health effects. The present study was designed to assess the protective effect of lycopene-enriched tomato paste against N-nitrosodiethylamine (NDEA)-induced oxidative stress in rats. Forty-eight male Wistar rats were divided randomly into six groups. Four groups were treated with tomato paste, per os, for 28 days in doses which were equivalent to 0.5 (groups II and V) and 2.5 mg/kg b.w./day of lycopene (groups III and VI). Rats from groups IV-VI were given intraperitoneally a single dose of NDEA, 150 mg/kg b.w. Group I (control) was given distilled water. Pretreatment with tomato paste protected the antioxidant enzymes: superoxide dismutase, catalase and glutathione reductase. Their activity was recovered by 32-97 %, as compared to NDEA-treated rats. Microsomal lipid peroxidation in the liver was decreased in rats pretreated with a lower dose of tomato paste by 28 %, as compared to animals given NDEA alone. Pretreatment with tomato paste caused a decrease in plasma concentration of protein carbonyls, even below the control level, in rats given NDEA. Moreover, a 10 % reduction of DNA damage in leucocytes caused by NDEA was observed. The tomato paste tested was able to suppress NDEA-induced oxidative stress in rats.

The effect of cloudy apple juice on hepatic and mammary gland phase I and II enzymes induced by DMBA in female Sprague-Dawley rats.

Apples abundant in phenolic compounds show a variety of biological activities that may contribute to health beneficial effects against cardiovascular diseases, diabetes, obesity and cancer. We investigated the effect of cloudy apple juice (CAJ) on the hepatic and mammary gland carcinogen metabolizing enzymes, DNA damage and liver injury, altered by 7,12-dimethylbenz[a]anthracene (DMBA). Sprague-Dawley female rats were gavaged with CAJ (10 ml/kg b.w.) for 28 consecutive days. DMBA was administered i.p. on the 27th and the 28th days. In the liver, feeding with CAJ decreased the activities of CYP1A1 and 1A2 and increased phase II enzymes. The activities of all enzymes tested were enhanced in the animals treated with DMBA alone and in combination with CAJ. The most significant changes in the level of the hepatic enzymes tested were observed for GST alpha and NQO1. In mammary gland CAJ induced an increase in the level of GST mu and GST pi, while DMBA and CAJ combined administration elevated GST pi only. This may be beneficial as GST pi is involved in the DMBA detoxification. Additionally, pretreatment with CAJ reduced the level of most of the blood biochemical liver and kidney markers elevated as a result of DMBA treatment. These findings indicate that CAJ may interfere with enzyme system involved in carcinogen metabolism. However, this effect seems to be dependent on tissue and carcinogen and is moderately effective in the case of DMBA. Moreover, CAJ can also provide some protection against the liver and kidney damage.

Evaluation of the effect of beetroot juice on DMBA-induced damage in liver and mammary gland of female Sprague-Dawley rats.

Red beetroot contains a specific class of antioxidants collectively named betalains, which have been shown to have anticarcinogenic and anti-inflamatory potential. We investigated the effect of beetroot juice on the hepatic and mammary gland carcinogen metabolizing enzymes, DNA damage and liver injury, altered by 7,12-dimethylbenz[a]anthracene (DMBA). In the liver, pretreatment with beetroot juice significantly decreased levels and activities of the majority of tested biochemical parameters, elevated by DMBA. Feeding with beetroot juice decreased the activities of CYP1A1 and 1A2 and increased phase II enzymes. The activities of all enzymes tested were enhanced in the animals treated with DMBA alone and in combination with beetroot juice. The most significant changes in the level of the enzymes tested were observed for NAD(P)H: quinone oxidoreductase-1. In mammary gland, beetroot juice induced the level of glutathione S-transferase pi, enzyme involved in active metabolites of DMBA detoxification. The final effects of beetroot juice are tissue specific and depend on the class of carcinogen.

Exposure to alcohol and tobacco smoke causes oxidative stress in rats.

BACKGROUND: Tobacco smoking and alcohol abuse causes oxidative stress in humans and underlay numerous chronic degenerative diseases. Liver is the main organ exposed to alcohol toxic metabolites, whereas tobacco smoke is chiefly harmful to the lungs. METHODS: The aim of the current study was the assessment and comparison of selected oxidative stress markers, reduced glutatione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase, nitrites and protein nitrosylation and DNA damage in the livers and in the lungs of alcohol-addicted rats exposed to tobacco smoke alone or in combination with a single dose of ethanol. RESULTS: The highest levels of GSH were measured in the liver of smoke only exposed animals and in the lungs of rats exposed to smoke and alcohol. In the liver of animals treated with a single dose of alcohol or with smoke and alcohol, GST was significantly higher than in the group exposed to smoke only. SOD and catalase showed the highest activities in the livers of rats receiving a single dose of alcohol. High concentration of nitrites was observed in the lungs of animals treated with smoke and alcohol in combination, which corresponded to elevated protein nitrosylation in this group, whereas in the livers of these animals relatively low level of nitrites was accompanied with the lowest concentration of nitrosylated proteins. In the liver of alcohol only treated rats the highest nitrites corresponded to the highest protein nitrosylation. In the lungs of all treatment groups the range of DNA damage was higher, than the respective values in the livers. Although alcohol is not considered a specific toxicant to the lungs it was found to cause oxidative stress in this organ. CONCLUSIONS: The obtained results suggest that in the ethanol-addicted rats combined exposure to smoke and alcohol differentially modulate endogenous antioxidant defense system and reactions to oxidative stress.

Attenuation of KBrO3-induced renal and hepatic toxicity by cloudy apple juice in rat.

The aim of the study was to evaluate a protective effect of apple juice on KBrO3-induced oxidative stress in rats. Male Wistar rats were administered apple juice per os, 10 ml/kg b.w. for 28 days. On 27 day of the experiment, some rats were given i.p. a single 125 mg/kg b.w. dose of KBrO3 . Markers of oxidative damage and clinical chemistry parameters were determined. Treatment with apple juice prior to KBrO3 challenge prevented an increase in hepatic and renal microsomal lipid peroxidation by 25 and 44%, respectively, increased the activity of antioxidant enzymes in the liver by 29 - 59% and decreased the plasma content of carbonyl groups by 19%. Aminotransferases activity in plasma was reduced by 19% and 36%, concentrations of plasma bilirubin, cholesterol and creatinine were suppressed by 21%, 16% and 26%, respectively, in rats supplemented with juice before KBrO3 injection. No protective effect of apple juice on nuclear DNA was observed. Supplementation with cloudy apple juice to some extent attenuated oxidative damage induced by KBrO3 in the liver and kidney of rats as evidenced by alterations of certain oxidative stress markers and clinical chemistry parameters.

Beetroot juice protects against N-nitrosodiethylamine-induced liver injury in rats.

Red beetroot, a common ingredient of diet, is a rich source of a specific class of antioxidants, betalains. Our previous studies have shown the protective role of beetroot juice against carcinogen induced oxidative stress in rats. The aim of this study was to examine the effect of long term feeding (28 days) with beetroot juice on phase I and phase II enzymes, DNA damage and liver injury induced by hepatocarcinogenic N-nitrosodiethylamine (NDEA). Long term feeding with beetroot juice decreased the activities of enzymatic markers of cytochrome P450, CYP1A1/1A2 and CYP2E1. NDEA treatment also reduced the activities of these enzymes, but increased the activity of CYP2B. Moreover, combined treatment with beetroot juice and NDEA enhanced significantly CYP2B only. Modulation of P450 enzyme activities was accompanied by changes in the relevant proteins levels. Increased level and activity of NQO1 was the most significant change among phase II enzymes. Beetroot juice reduced the DNA damage increased as the result of NDEA treatment, as well as the biomarkers of liver injury. Collectively, these results confirm the protective effect of beetroot juice against oxidative damage shown in our previous studies and indicate that metabolic alterations induced by beetroot feeding may protect against liver damage.

[Selected biochemical parameters of oxidative stress as a result of exposure to tobacco smoke in animals addicted to ethyl alcohol]. / Wybrane parametry biochemiczne stresu oksydacyjnego w wyniku ekspozycji na dym tytoniowy zwierzat uzaleznionych od alkoholu etylowego.

Smoking cigarettes and alcohol addiction are serious problems in health hazard and life of society. Tobacco smoke leads to many kinds of cancer formation and scientific research indicates, that heart-vascular disease and lung cancer are the most common diseases caused by tobacco smoke. While talking about ethanol, it is responsible for liver, pancreas, mucous membrane damage and leads to central and circular nervous disorder. Scientific research indicates, that many smokers drink alcohol and vice versa. Unfortunately in that case the risk of many diseases increases. Both of these stimulants leads to enlarged production of reactive oxygen species, which is connected with unbalance between pro and antioxidant processes in human organism. Free radicals in normal conditions plays positive role but with tobacco smoke and alcohol connection may lead to serious changes in human organism. They damage organs, it comes to protein structure, nucleic acid and fat violation, which in consequence leads to immunity decrease and many pathological changes. Reactive oxygen species also plays role in pathogenesis of many diseases: diabetes mellitus, atherosclerosis and Down syndrome. ROS may also increase the risk of pancreas, lung, larynx and urinary bladder cancer formation. Human organism defends oneself from harmful influence of reactive oxygen species owing to enzymatic and non-enzymatic systems presence-Non-enzymatic antioxidants: glutathione, carotene, bilirubin, tocopherol, uric acid and ions metals temporary complex belong to non-enzymatic systems. To enzymatic ones belong: catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase. The aim of the study was tobacco smoke and ethyl alcohol influence evaluation in rats addicted to these substances on activity of chosen enzymes responsible for organism defense against toxic compounds action. To this study 63 white, Wistar tribe rats at the age of 3,5 months were used - males addicted to ethyl alcohol. They were divided into 3 groups, each consist of 21 rats. Animals of Group I were exposed on harmful tobacco smoke influence. Group II constitute animals, which were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. The next Group - III, in which animals at first were exposed on tobacco smoke influence. When exposition was over, animals were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. Depending on the type of marker and studied organ, changes in the levels of selected enzymes, responsible for defending organism against reactive forms of oxygen has been shown. Both tobacco smoke and ethyl alcohol resulted in a change of glutathione levels in the serum and tissues of animals. Tobacco smoke has the biggest influence on protein nitrozylation in the brain and ethyl alcohol had influence on glutathione level in serum, kidney, brain and superoxide dismutase activity in the brain. Application of many oxidative stress markers allows for evaluation of its differential influence on various organs.

Chokeberry (Aronia melanocarpa) juice modulates 7,12-dimethylbenz[a]anthracene induced hepatic but not mammary gland phase I and II enzymes in female rats.

Chokeberry is a rich source of procyanidins known to have several types of biological activity including anticarcinogenic potential in experimental models. In this study we examined the effect of chokeberry juice on the hepatic and mammary gland carcinogen metabolizing enzyme expression altered by the polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA). Sprague-Dawley rats were gavaged with chokeberry juice (8 ml/kg b.w.) for 28 consecutive days. DMBA was administered i.p. on the 27th and the 28th days. Pretreatment with chokeberry juice reduced the activity of CYP1A1 and increased that of CYP2B involved in metabolic activation/detoxication of DMBA in rat liver, as well as expression and activity of phase II enzymes. Chokeberry juice had no effect on these parameters in the mammary gland and DMBA induced DNA damage in rat blood cells. These results together with our earlier observations indicate that metabolic alterations induced by chokeberry feeding are tissue specific and depend on the class of carcinogen.

Protein kinase Cε as a cancer marker and target for anticancer therapy.

Protein kinase Cε (PKCε) is a representative member of a family of novel PKC isoforms that are independent of calcium, but can be activated by phorbol esters, diacylglycerol (DAG) and phosphatidylserine (PS). This kinase is capable of modulating crucial cell functions, including proliferation, differentiation and survival. These activities depend on enzyme translocation to subcellular compartments upon binding DAG, PS or exogenous stimulators. PKCε initiates malignant transformation of cells through its effects on the Ras/Raf/MAPK pathway and displays the greatest carcinogenic potential of all PKC isoforms. PKCε also promotes tumor metastatic capacity and resistance to anti-cancer therapy. Overexpression of PKCε is found in numerous cancers including colon, breast, stomach, prostate, thyroid and lung and is considered an important marker of negative disease outcome. Although overexpression of PKCε is observed in tumors, it is not found in healthy tissues hence it has been suggested as a diagnostic marker or a putative target for specific inhibitors used for treatment of cancer. Research on selective inhibition of PKCε is under way and diverse approaches may become clinically applicable anti-tumor strategies. Suppression of the PKCε-encoding gene achieved through the antisense cDNA, suppression of PKCε with RNAi and inhibition achieved with translocation-inhibitory peptides may provide novel treatment strategies for cancer.

Protective effect of chokeberry on chemical-induced oxidative stress in rat.

Male Wistar rats were treated with chokeberry juice per os, 10 mL/kg/day, for 28 days and a single intraperitoneal (i.p.) dose of N-nitrosodiethylamine (NDEA), 150 mg/kg, or carbon tetrachloride (CCl(4)), 2 ml/kg. The level of hepatic microsomal lipid peroxidation, expressed as thiobarbituric acid reactive substances (TBARS), was increased in animals dosed with NDEA and CCl(4). Juice pretreatment resulted in a significant decrease in TBARS by 53% and 92%, respectively. In rats administered juice alone, 50% decrease in TBARS was noted. The activities of all antioxidant enzymes were decreased in the liver of rats administered either toxicant by 29%-52% as compared to controls. Juice pretreatment resulted in an increase in the activity of catalase, glutathione peroxidase and glutathione reductase by 117%, 56% and 44%, respectively, only in rats challenged with NDEA. Although no response of plasma protein carbonyls to both toxicants was observed, the pretreatment with juice caused a 55% decrease of this parameter in CCl(4)-dosed rats. DNA damage in blood leukocytes induced by either toxicant was slightly reduced, by 24%, in the rats pretreated with juice and administered NDEA. The results of the study showed that pretreatment with chokeberry juice confers some protection against chemical-induced oxidative stress.

Cloudy apple juice protects against chemical-induced oxidative stress in rat.

BACKGROUND: Apples abundant in phenolic compounds show a variety of biological activities that may contribute to beneficial effects against some chronic diseases. PURPOSE: The aim of our study was to assess the protective effect of cloudy apple juice against chemical-induced oxidative stress in rats. METHODS: Male Wistar rats were treated with apple juice per os, 10 mL/kg/day for 28 days and with a single dose of N-nitrosodiethylamine (NDEA), 150 mg/kg or carbon tetrachloride (CCl(4)), 2 mL/kg, 24 h before killing. Two groups of rats not pretreated with juice were administered each of the xenobiotics alone. RESULTS: Microsomal lipid peroxidation in the liver was decreased in rats pretreated with juice by 52-87% when compared to animals given NDEA or CCl(4) alone. Pretreatment with juice protected antioxidant enzymes: catalase, glutathione peroxidase and glutathione reductase but not superoxide dismutase. Their activity was recovered by 49-173% when compared to that in rats given either toxicant alone. The plasma activity of paraoxonase 1 was reduced by both toxicants and was increased by 23% in the apple/CCl(4) group. A rise in plasma protein carbonyls caused by the xenobiotics was reduced by 20% only in apple/NDEA-treated rats. Also, in this group of animals, a 9% decrease in DNA damage in blood leukocytes was observed. CONCLUSION: Phytochemicals in commonly consumed apple juice may protect some macromolecules against oxidative insult induced by xenobiotics.