Effects of desipramine on the antioxidant status in rat tissues at carrageenan‐induced paw inflammation

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)‐induced inflammation, as well as on the endogenous levels of cell enzyme and non‐enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra‐plantar CG injection into the right hind paw resulted in a time‐dependent increase in the paw volume; the maximum of CG‐induced edema peak was in 2–4 h. A single DES dose of 20 mg·kg^?1, administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg·kg^?1) suppressed the edematous response to CG. The latter drug dose protected CG‐induced decrease of glutathione (non‐enzyme antioxidant) in the liver; it did not affect CG‐unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose‐6‐phosphate dehydrogenase (enzyme, important for the activity of glutathione‐conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS‐generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries. Copyright © 2011 John Wiley & Sons, Ltd.     

In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

The effects of nociceptin(1–13)NH₂ (N/OFQ(1–13)NH₂) and its structural analogue [Orn⁹]N/OFQ(1–13)NH₂ on acute carrageenan (CG)-induced peripheral inflammation and paw antioxidant status were studied. CG was injected intraplantarly in the right hind paw of rats and the volume of the inflamed paw was measured each 30 min for a period of 4h. When administered simultaneously with CG, N/OFQ(1–13)NH₂ decreased the paw volume, whereas if injected 15 min before CG it had no effect. [Orn₉]N/OFQ(1–13)NH₂ produced the opposite effects at the same time-intervals of its administration. We also investigated whether these neuropeptides influence CG-induced changes in cell antioxidant system, especially at the 4th hour of CG administration. CG alone decreased the glutathione level and superoxide dismutase activity, as measured in post-nuclear homogenate of the inflamed paw. However, CG injection increased glutathione peroxidase and glucose-6-phospate dehydrogenase activities, while the activity of glutathione reductase was unchanged. The peptides themselves did not change all measured parameters. Moreover, neither N/OFQ(1–13)NH₂ nor [Orn⁹]N/OFQ(1–13)NH₂ modified CG-induced changes in the antioxidant status, regardless of the time of their injection (simultaneously or 15 min before CG). The present results suggest that N/OFQ(1–13)NH₂ and [Orn⁹]N/OFQ(1–13)NH₂ most likely affect the neuronal inflammation, rather than act as pro- or antioxidants.     

Pre treatment with Bacillus subtilis mitigates drought induced photo-oxidative damages in okra by modulating antioxidant system and photochemical activity

Growth promoting potential of Bacillus subtilis (BS) in drought stressed Abelmoschus esculentus (L.) Moench (okra) was assessed by measuring the chlorophyll stability index (CSI), chlorophyll a (Chl-a) fluorescence, leaf osmotic potential and lipid peroxidation by malondialdehyde content, emission of reactive oxygen species (ROS), osmolyte content and the activity of non-enzyme and enzyme antioxidants. BS treatment significantly increased the leaf osmotic potential, osmolyte production and the activity of non-enzyme and enzyme antioxidants under drought stress. BS treatment mitigated the drought-induced reduction in Chl a fluorescence and CSI. Concomitant increase in total sugar, proline, non-enzyme antioxidants [glutathione and ascorbate] and enzyme antioxidants like superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase modulate the intracellular ROS concentration in okra to resist the stress induced oxidative damage in BS treated plants led to fast recovery and less photodamage.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-00982-8.     

Semecarpus anacardium nut extract promotes the antioxidant defence system and inhibits anaerobic metabolism during development of lymphoma

Antioxidants are substances that fight against ROS (reactive oxygen species) and protect the cells from their damaging effects. Production of ROS during cellular metabolism is balanced by their removal by antioxidants. Any condition leading to increased levels of ROS results in oxidative stress, which promotes a large number of human diseases, including cancer. Therefore antioxidants may be regarded as potential anticarcinogens, as they may slow down or prevent development of cancer by reducing oxidative stress. Fruits and vegetables are rich source of antioxidants. Moreover, a number of phytochemicals present in medicinal plants are known to possess antioxidant activity. Therefore the aim of the present study was to investigate antioxidant activity of the aqueous extract of nuts of the medicinal plant Semecarpus anacardium in AKR mouse liver during the development of lymphoma. Antioxidant action was monitored by the activities of antioxidant enzymes catalase, superoxide dismutase and glutathione transferase. The effect of S. anacardium was also studied by observing the activity of LDH (lactate dehydrogenase), an enzyme of anaerobic metabolism. LDH activity serves as a tumour marker. The activities of antioxidant enzymes decreased gradually as lymphoma developed in mouse. However, LDH activity increased progressively. Administration of the aqueous extract of S. anacardium to lymphoma-transplanted mouse led to an increase in the activities of antioxidant enzymes, whereas LDH activity decreased significantly, indicating a decrease in carcinogenesis. The aqueous extract was found to be more effective than doxorubicin, a classical anticarcinogenic drug, with respect to its action on antioxidant enzymes and LDH in the liver of mice with developing lymphomas.     

Developmental expression of antioxidant enzymes in guinea pig lung and liver

Antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total glutathione concentration were determined in guinea pig lung and liver over the final period of gestation (days 50-68) and at several ages post-partum. Pulmonary antioxidant capacity increased markedly over the final days of gestation, individual changes ranging from 29% (glutathione) to 198% (GSH-Px). Liver antioxidant capacity was always 4-fold to 10-fold greater than that of the lung and exhibited very similar developmental profiles to those observed in the lung. From day 60 gestation to term (68 days), activity of the liver antioxidants increased, ranging from 246% (CAT) to 610% (glutathione). A number of antioxidants in both lung and liver exhibited either immediate pre- or post-birth decreases in activity. These falls could not be attributed to the way in which the results were expressed: i.e. they were similar, expressed per unit DNA, per unit protein, or per g wet wt. Following birth, liver antioxidant capacity increased such that the highest enzyme activities or glutathione concentration were recorded at 66 days post-partum. In lung, only Mn-SOD and glutathione exhibited higher levels at 66 days postpartum than at birth. In combination, these results of pulmonary and hepatic antioxidant enzyme activity indicate that the lung is not unique in acquiring increased antioxidant protection in the final period of gestation. They also suggest that a tissue's antioxidant requirement is dictated more by metabolic rate (hence free radical production) than incident partial pressure of oxygen.     

Antioxidant levels in the rat brain after nitric oxide synthase inhibition: a preliminary report

Protective effects of NOS inhibitors and free radical scavengers in cerebral ischemia are well documented. The present study was undertaken to determine the possible effects of NOS inhibition on brain antioxidants. Levels of both enzymatic [glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)] and non-enzymatic [reduced glutathione (GSH)] antioxidants following nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME), D-NAME or 7-nitroindazole (7-NI) have been investigated. NOS activity and antioxidant levels in the rat cerebellum and medulla were estimated 1 h after treatment with L-NAME (10, 30 and 100 mg/kg, i.p.), D-NAME (100 mg/kg, i.p.) or 7-NI (25 mg/kg, i.p.). L-NAME and 7-NI inhibited NOS activity in a dose-dependent manner. D-NAME also exhibited significant NOS inhibition. The activity of SOD and the GSH level remained unaltered following NOS inhibition. However, L-NAME and D-NAME at 100 mg/kg attenuated GPx activity in the cerebellum, though 7-NI had no effect. L-NAME inhibited catalase activity in medulla only at 30 mg/kg, but had no effect in cerebellum. However, 7-NI (25 mg/kg), D-NAME and L-NAME at 100 mg/kg did not affect catalase activity in the rat brain. Thus, NOS inhibition by the three agents did not have major effects on brain antioxidant levels.     

Regulation of Free Radical Processes by Delta-Sleep Inducing Peptide in Rat Tissues under Cold Stress

An intraperitoneal injection of an exogenous delta-sleep inducing peptide (DSIP) at a dose of 12 g/100 g body weight shifted the prooxidant–antioxidant balance of free radical process (FRP) in tissues and erythrocytes of rats: the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the concentrations of antioxidants (reduced glutathione in particular) increased. The DSIP stimulated the myeloperoxidase activity in blood neutrophils and had no effect on the activity of xanthine oxidase, a prooxidant enzyme, in the brain and liver. Cold stress displaced the prooxidant–antioxidant balance by increasing the xanthine oxidase activity in tissues and decreasing the myeloperoxidase activity in blood neutrophils; it also inhibited the enzyme antioxidant activities in tissues and erythrocytes that was neutralized by an increased ceruloplasmin activity in blood plasma and by an elevated level of antioxidants in rat blood and tissues. Preliminary administration of DSIP to animals exposed to cold stress restored the prooxidant–antioxidant balance: it normalized the myeloperoxidase activity in blood neutrophils, decreased the xanthine oxidase activity, and increased the activity of antioxidant enzymes in tissues and erythrocytes restoring the antioxidant level. The molecular regulation mechanism of free radical processes by DSIP in tissues under stressful conditions is discussed.     

Vitamin C, resveratrol and lipoic acid actions on isolated rat liver mitochondria: all antioxidants but different

Modulating mitochondrial antioxidant status is a nutritional issue of great interest in the treatment or prevention of several oxidative stress related diseases such as obesity. Thus, the aim of the present study was to analyze the effects of three antioxidants on hepatic mitochondrial function and antioxidant status. Isolated rat liver mitochondria were incubated with vitamin C, resveratrol and lipoic acid. The activity of antioxidant enzymes (manganese superoxide dismutase and glutathione peroxidase), ROS generation and respiratory parameters (RCR, P/O ratio and respiratory states) were measured. Vitamin C influenced mitochondrial function by decreasing of ROS generation (P < 0.0001), by stimulating the activity of manganese superoxide dismutase (197.60 ± 35.99%; P < 0.001) as well as glutathione peroxidase (15.70 ± 5.76%; P < 0.05) and by altering the activity of the electron transport chain, mainly by decreasing the P/O ratio (P < 0.05). Resveratrol induced a significant increase in manganese superoxide dismutase activity (160 ± 11.78%; P < 0.0001) and a decrease in ROS generation (P < 0.05 to P < 0.0001). By contrast, lipoic acid inhibited glutathione peroxidase activity (16.48 ± 3.27%; P < 0.05) and induced the uncoupling of the electron transport chain (P < 0.01). Moreover, this antioxidant induced a strong decrease in the P/O ratio (P < 0.05 to P < 0.0001). In conclusion, our results suggest that the three tested antioxidants produced direct effects on mitochondrial function, although the magnitude and intensity of these actions were significantly different, which may have implications when administrated as antioxidants.     

Antiperoxidative and antioxidant effects of Casearia esculenta root extract in streptozotocin-induced diabetic rats

Oxidative stress is currently suggested to play as a pathogenesis in the development of diabetes mellitus. The present study was designed to evaluate the effect of Casearia esculenta root extract on oxidative stress-related parameters in streptozotocin (STZ) -induced diabetic rats. Antidiabetic treatment with C. esculenta root extract (45 days) significantly (p < .05) decreased thiobarbituric acid reactive substances (TBARS) and remarkably improved tissue antioxidants status such as glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) in liver and kidney of STZ-diabetic rats. In diabetics rats, the activities of enzymatic antioxidants such as superoxide dismutase (SOD, EC 1.11.1.1) catalase (CAT, EC 1.11.1.6) were decreased significantly while the activity of glutathione peroxidase (GPx, EC 1.11.1.9) decreased in the liver and increased in the kidney. The treatment of diabetic rats with C. esculenta root extract over a 45-day period returned these levels close to normal. These results suggest that C. esculenta root extracts exhibit antiperoxidative as well as antioxidant effects in STZ-induced diabetic rats.     

Antioxidant levels in the rat brain after nitric oxide synthase inhibition: a preliminary report

Abstract

Protective effects of NOS inhibitors and free radical scavengers in cerebral ischemia are well documented. The present study was undertaken to determine the possible effects of NOS inhibition on brain antioxidants. Levels of both enzymatic [glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)] and non-enzymatic [reduced glutathione (GSH)] antioxidants following nitric oxide synthase (NOS) inhibition by N^G-nitro-L-arginine methyl ester (L-NAME), D-NAME or 7-nitro-indazole (7-NI) have been investigated. NOS activity and antioxidant levels in the rat cerebellum and medulla were estimated 1 h after treatment with L-NAME (10, 30 and 100 mg/kg, i.p.), D-NAME (100 mg/kg, i.p.) or 7-NI (25 mg/kg, i.p.). L-NAME and 7-NI inhibited NOS activity in a dose-dependent manner. D-NAME also exhibited significant NOS inhibition. The activity of SOD and the GSH level remained unaltered following NOS inhibition. However, L-NAME and D-NAME at 100 mg/kg attenuated GPx activity in the cerebellum, though 7-NI had no effect. L-NAME inhibited catalase activity in medulla only at 30 mg/kg, but had no effect in cerebellum. However, 7-NI (25 mg/kg), D-NAME and L-NAME at 100 mg/kg did not affect catalase activity in the rat brain. Thus, NOS inhibition by the three agents did not have major effects on brain antioxidant levels.     

Comparison of the effects of melatonin and pentoxifylline on carbon tetrachloride-induced liver toxicity in mice

The purpose of the study was to determine whether along and in combination melatonin (MLT) and pentoxlfylline (PTX) exerted beneficial effects on histopathological changes and changes in oxidant and antioxidant systems in liver caused by CCl₄-induced liver toxicity in mice. Mice were randomly divided into six groups: control, olive oil, toxicity, MLT, PTX, PTX+MLT. MLT 10 mg/kg/day, PTX 50 mg/kg/day, and the same individual doses in MLT+PTX combination were given intraperitoneally to mice for 7 day. CCl₄ 0.8 mg/kg/day was administered on the 4th, 5th, and 6th days of therapy in all groups except the control and olive oil groups. In the toxicity group, increased concentrations of malondialdehyde (MDA) and lipid hydroperoxides (LOOH) and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found compared to the control and olive oil groups (p < 0.05). Compared to the toxicity group, both the PTX group and the PTX+MLT group had decreased MDA and LOOH levels, whereas MLT reduced only LOOH levels (p < 0.01). MLT, PTX and MLT+PTX increased the GSH-Px and CAT activities compared to the toxicity group (p < 0.05). MLT increased CAT activity compared to PTX and MLT+PTX (p < 0.05). Superoxide dismutase enzyme activity did not change in any group (p < 0.05). Histopatholically, ballooning, degeneration, apoptosis, and bridging necrosis were seen in the toxicity group. MLT, PTX and MLT+PTX decreased the apoptosis and bridging necrosis (p < 0.01), and PTX and MLT+PTX decreased balloon degeneration compared to the toxicity group (p < 0.01). These results indicate that administration of PTX and MLT alone and in combination before onset of liver toxicity might prevent the oxidative damage by reducing oxidative stress and increasing antioxidant enzyme levels.     

Lactobacillus protected bone damage and maintained the antioxidant status of liver and kidney homogenates in female wistar rats

The aim of the study was to evaluate protective property of Lactobacillus casei and Lactobacillus acidophilus in minimizing oxidative stress associated with arthritis from liver and kidney. Subsequently, protective property of Lactobacillus against the bone damage was also taken into consideration. Arthritis was induced by injecting freund's complete adjuvant (100 μl) into sub plantar surface of hind paw. Oral administration of culture, vehicle, and drug started after induction of arthritis (i.e. on day 9th). Indomethacin was used as a standard drug. Radiographic analysis of the hind paw knee joint was also done at the end of the 21st day. Oxidative stress parameters were studied from liver and kidney homogenate. Histopathology of liver and kidney was also performed. Lactobacillus treatment significantly rescued the enzymatic level of catalase, superoxide dismutase, reduced glutathione, and glutathione peroxidase in both liver and kidney homogenates, whereas it has decreased the malonaldehyde accumulation. Oral administration of Lactobacillus also significantly decreased the serum ceruloplasmin level. Radiographic analysis also corroborated these findings. Lactobacillus treatment maintained the normal histopathology of liver and kidney. Results of this study clearly suggest that L. casei and L. acidophilus, alone or in combination, decreased the bone damaged and effectively restored antioxidant status of liver and kidney. Lactobacillus has a significant antiarthritic and antioxidant activity against freund's complete adjuvant induced arthritis in rats.     

Thiol supplementation in aged animals alters antioxidant enzyme activity after heat stress.

Declines in oxidative and thermal stress tolerance are well documented in aging systems. It is thought that these alterations are due in part to reductions in antioxidant defenses. Although intracellular thiols are major redox buffers, their role in maintaining redox homeostasis is not completely understood, particularly during aging, where the reliance on antioxidant enzymes and proteins may be altered. To determine whether thiol supplementation improved the antioxidant enzyme profile of aged animals after heat stress, young and old Fischer 344 rats were treated with N-acetylcysteine (NAC; 4 mmol/kg ip) 2 h before heat stress. Liver tissue was collected before and 0, 30, and 60 min after heat stress. Aging was associated with a significant decline in tissue cysteine and glutathione (GSH) levels. There was also an age-related decrease in copper-zinc superoxide dismutase activity. Heat stress did not alter liver GSH, glutathione disulfide, or antioxidant enzyme activity. With NAC treatment, old animals took up more cysteine than young animals as reflected in an increase in liver GSH and a corresponding decrease in glutamate cysteine ligase activity. Catalase activity increased after NAC treatment in both age groups. Copper-zinc superoxide dismutase activity did not change with heat stress or drug treatment, whereas manganese superoxide dismutase activity was increased in old animals only. These data indicate that GSH synthesis is substrate limited in old animals. Furthermore, aged animals were characterized by large fluctuations in antioxidant enzyme balance after NAC treatment, suggesting a lack of fine control over these enzymes that may leave aged animals susceptible to subsequent stress.     

Responses of glutathione system and antioxidant enzymes to exhaustive exercise and hydroperoxide.

Glutathione (gamma-glutamylcysteinylglycine) is one of the major antioxidants in the body. The present study investigated the changes of glutathione status, oxidative injury, and antioxidant enzyme systems after an exhaustive bout of treadmill running and/or hydroperoxide injection in male Sprague-Dawley rats. Concentrations of total and reduced glutathione in deep vastus lateralis muscle were significantly increased (P less than 0.01) after exhaustive exercise with either hydroperoxide (t-butyl hydroperoxide) or saline injection, whereas hydroperoxide alone had no significant effect. Exhaustive exercise increased muscle glutathione disulfide content by 75 and 60% (P less than 0.05), respectively, in hydroperoxide and saline groups. Concentrations of glutathione-related amino acids glutamate, cysteine, and aspartate were significantly increased in the same muscle after exhaustion. Hepatic glutathione status was not affected by either hydroperoxide injection or exercise. Glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase activities were significantly elevated after exhaustive exercise with or without hydroperoxide injection in muscle but not in liver. Hydroperoxide and exhaustive exercise enhanced lipid peroxidation in muscle and liver, respectively. It is concluded that exhaustive exercise can impose a severe oxidative stress on skeletal muscle and that glutathione systems as well as antioxidant enzymes are important in coping with free radical-mediated muscle injury.     

Cardiotoxicity of doxorubicin/paclitaxel combination in rats: effect of sequence and timing of administration

The higher incidence of cardiotoxicity of doxorubicin (DOX)/paclitaxel (PTX) combination compared with DOX alone remains to be a major obstacle against effective chemotherapeutic treatment. We investigated the effect of sequence and time interval between administration of both drugs on the severity of cardiotoxicity of the combination. Male Wistar rats were divided into seven groups. DOX was administered intraperitoneally (i.p.) at a single dose of 5 mg x kg(-1) every other 2 days, 2 doses per week for a total cumulative dose of 20 mg x kg(-1). PTX was administered by an i.p. route at a dose of 20 mg x kg(-1) every other 2 days. Both drugs were injected either alone or sequentially in combination. In one case, DOX preceded PTX by 30 min and 24 h and in the other case, PTX preceded DOX by 30 min and 24 h. Cardiotoxicity was evaluated by both biochemical and histopathological examination, 48 h after the last DOX dose. DOX-induced cardiotoxicity was manifested by abnormal biochemical changes including marked increases in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and aspartate aminotransferase (AST) activity levels. Myocardial tissue from DOX-treated rats showed significant increases in malondialdehyde (MDA) production and total nitrate/nitrite (NOx) levels, parallel with depletion of "endogenous antioxidant reserve," including GSH contents and GSH-Px activity level. PTX treatment produced significant changes in the biochemical parameters measured by a lower magnitude than those changes produced by DOX alone. Combination of both drugs resulted in aggravation of DOX-induced cardiotoxicity regardless the sequence and time interval between administration of either drug. Administration of PTX 30 min and 24 h after DOX treatment showed exaggeration of combination-induced cardiotoxicity compared with the reverse sequence. This exacerbation was manifested by much more pronounced changes in serum and cardiac tissue parameters measured. Histopathological examination of ventricles of rat's heart revealed that DOX treatment produced myo-cytolysis and myocardial necrosis. Administration of PTX following DOX treatment showed extensive myocardial necrosis compared with those rats treated with either DOX alone or the reverse sequence of administration. Moreover, rats treated with PTX 24 h after DOX treatment showed exaggeration of the combination-induced cardiotoxicity. In conclusion, PTX might synergistically aggravate DOX-induced cardiotoxicity. The effect might be much more pronounced with those rats treated with PTX 24 h after DOX treatment.     

Effects of new antioxidant compounds PNU-104067F and PNU-74389G on antioxidant defense in normal and diabetic rats

Diabetes mellitus and its complications are associated with elevated oxidative stress, leading to much interest in antioxidant compounds as possible therapeutic agents. Two new classes of antioxidant compounds, the pyrrolopyrimidines and the 21-aminosteroids, are known to inhibit lipid peroxidation and other biomolecular oxidation. We hypothesized that in the presence of excess oxidants or the impaired antioxidant defense seen in diabetes mellitus, administration of antioxidants such as these may reverse the effects of diabetes on antioxidant parameters. This study measured the effects of subchronic (14 day) treatment with a pyrrolopyrimidine (PNU-104067F) or a 21-aminosteroid (PNU-74389G) in normal and diabetic Sprague-Dawley rats. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, concentrations of oxidized and reduced glutathione, and lipid peroxidation were used as measures of antioxidant defense in liver, kidney, heart, and brain tissue. In normal rats, the only effect was a 43% increase in cardiac lipid peroxidation after treatment with PNU-104067F. In diabetic rats, the only reversals of the effects of diabetes were a 30% decrease in hepatic glutathione peroxidase activity after PNU-74389G treatment and a 33% increase in cardiac glutathione disulfide concentration after PNU-104067F treatment. In contrast to these effects, increased cardiac glutathione peroxidase and catalase activities, increased brain glutathione peroxidase activity, increased hepatic lipid peroxidation, decreased hepatic glutathione content, and decreased hepatic catalase activity were seen in diabetic rats, reflecting an exacerbation of the effects of diabetes.     

Hepatotoxic effects of CCl4 on English sole (Parophrys vetulus): possible indicators of liver dysfunction

Selected serum parameters (enzyme activities and triglycerides) and liver glutathione and vitamin C concentrations were measured in English sole (Parophrys vetulus) after i.p. injection of carbon tetrachloride (CCl4), a hepatotoxin in fish. Serum lactate dehydrogenase (LDH), alkaline phosphatase (AP) and glutamate dehydrogenase (GDH) activities and the concentration of triglycerides increased in a dose-dependent manner 24 hr post injection. Concentrations of glutathione (reduced and oxidized) and ascorbic acid (vitamin C) in liver did not change in response to CCl4 toxicity 24 hr post injection. These studies indicate that serum AP activity and triglyceride concentrations can be useful in assessing the effects of CCl4-induced liver toxicity in this species of marine fish. Serum LDH and GDH activity should be used with some caution in assessing liver damage in English sole, as other tissues represent more likely sources for serum activity. The levels of liver antioxidants do not appear to be significantly affected, 24 hr post injection, by this particular hepatotoxin.     

Influence of treatment of diabetic rats with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid on parameters of oxidative stress

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague-Dawley rats, normal and streptozotocin-induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, beta-carotene, pycnogenol + beta-carotene, or pycnogenol + beta-carotene + alpha-lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with beta-carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) beta-carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects.     

Induction of hepatic antioxidants in freshwater catfish (Channa punctatus Bloch) is a biomarker of paper mill effluent exposure

Enzymatic and non-enzymatic antioxidants serve as an important biological defense against environmental oxidative stress. Information on antioxidant defense in fish is meager despite that fish are constantly exposed to a myriad of environmental stress including the oxidants. This study, therefore, assesses the activities of antioxidant enzymes viz., glutathione peroxidase, catalase and glutathione S-transferase and the non-enzymatic antioxidants viz., glutathione and metallothionein in various tissues of freshwater fish Channa punctatus (Bloch), in response to short-term and long-term exposures to paper mill effluent. The fish were exposed to the effluent at a concentration of 1.0% (v/v) for 15, 30, 60 and 90 days. The exposure caused a time-dependent increase in glutathione level (P < 0.001), activities of glutathione peroxidase (P < 0.05 to P < 0.001), glutathione S-transferase (P < 0.001) and a marginal initial decrease in catalase activity in the liver (P < 0.01 to P < 0.001). Metallothionein was induced in liver after 60 days of exposure. Two isoforms of metallothionein were detected. Catalase activity also increased 60 days afterwards. Antioxidant pattern was different in gill and kidney showing that liver was more resistant to oxidative damage as compared to gills and kidney. Our results demonstrate a pollutant-induced adaptive response in fish. In addition, levels of enzymatic and non-enzymatic tissue antioxidants may serve as surrogate markers of exposure to oxidant pollutants in fish.