Effects of swimming activity and feed restriction on antioxidant and digestive enzymes in juvenile rainbow trout: Implications for nutritional and exercise strategies in aquaculture.

BACKGROUND: In this study, we investigated the effects of swimming activity and feed restriction on digestion and antioxidant enzyme activities in juvenile rainbow trout (average body weight of 26.54 ± 0.36 g). METHODS: The stomach, liver and kidney tissues were obtained from four distinct groups: the static water group (fish were kept in static water and fed to satiation), the feeding restricted group (fish were kept in static water with a 25% feed restriction), the swimming exercised group (fish were forced to swimming at a flow rate of 1 Body Length per second (BL/s)) and the swimming exercised-feed restricted group (subjected to swimming exercise at a 1 BL/s flow rate along with a 25% feed restriction). We determined the levels of glutathione, lipid peroxidation and the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and lactate dehydrogenase, as well as the presence of reactive oxygen species in the tissues obtained from the fish. Additionally, the activities of pepsin, protease, lipase and arginase in these tissues were measured. RESULTS: Swimming activity and feed restriction showed different effects on the enzyme activities of the fish in the experimental groups. CONCLUSION: It can be concluded that proper nutrition and exercise positively influence the antioxidant system and enzyme activities in fish, reducing the formation of free radicals. This situation is likely to contribute to the fish's development.

Melatonin improves liver and pancreatic tissue injuries in diabetic rats: role on antioxidant enzymes.

Purpose: Melatonin (Mel) is an indolamine mainly synthesized by the pineal gland and many other organs. It plays an important role in scavenging free radicals and stimulating antioxidant enzymes. The goal of this study was to investigate the effect of Mel and/or insulin treatment on oxidative liver and pancreas injuries in diabetic rats. Methods: Male Wistar albino rats were assigned into 5 groups. Group I: control animals. Group II: diabetes was induced via a single dose of STZ (60 mg/kg) administered intraperitoneally. Group III: diabetic rats treated with Mel (10 mg/kg/day). Group IV: diabetic rats given insulin (6U/kg) subcutaneously. Group V: diabetic rats that received insulin and Mel at the same dose and time. After 12 weeks of the experiment, the animals were decapitated, liver and pancreas tissues were collected. Results: The results indicated that reduced glutathione levels in liver and pancreatic tissue decreased, while protein carbonyl, advanced oxidized protein products and lipid peroxidation levels were elevated in diabetic group. Antioxidant enzyme activities decreased in liver tissues but increased in pancreatic tissues of the diabetic group. Administration of Mel, insulin or Mel + insulin reversed these biochemical changes in the diabetic animals. Conclusion: This work shows that in long-term oxidative stress conditions caused by STZ-induced diabetes, either Mel or Mel + insulin administration may improve the deteriorated oxidant/antioxidant system in both the liver and pancreas tissues. These results suggested that Mel alone or Mel + insulin treatments might have a significant role in protecting against liver and pancreatic damage in STZ diabetic rats via different antioxidant effects.

Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver.

The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n = 5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.

Oxidative brain and cerebellum injury induced by d-galactosamine: Protective effect of S-methyl methionine sulfonium chloride.

The objective of this study was to examine the protective effects of S-methyl methionine sulfonium chloride (MMSC) against galactosamine (GalN)-induced brain and cerebellum injury in rats. A total of 22 female Sprague-Dawley rats were randomly divided into four groups as follows: Group I (n = 5), intact animals; Group II (n = 6), animals received 50 mg/kg/day of MMSC by gavage technique for 3 consecutive days; Group III (n = 5), animals injected with a single dose of 500 mg/kg of GalN intraperitoneally (ip); and Group IV (n = 6), animals injected with the same dose of GalN 1 h after MMSC treatment. After 6 h of the last GalN treatment (at the end of the experiments), all animals were killed under anesthesia, brain and cerebellum tissues were dissected out. Reduced glutathione, total antioxidant status levels, and antioxidant enzymes (catalase, superoxide dismutase, and glutathione-related enzymes), aryl esterase, and carbonic anhydrase activities remarkably declined whereas advanced oxidized protein products, reactive oxygen species, total oxidant status, oxidative stress index levels, and myeloperoxidase, acetylcholinesterase, lactate dehydrogenase, and xanthine oxidase activities were significantly elevated in the GalN group compared with intact rats. In contrast, the administration of MMSC to GalN groups reversed these alterations. In conclusion, we may suggest that MMSC has protective effects against GalN-induced brain and cerebellar toxicity in rats.

Zinc Prevents Ethanol-Induced Oxidative Damage in Lingual Tissues of Rats.

The current study was designed to investigate the effects of zinc sulfate on cell proliferation, metallothionein (MT) immunoreactivity and antioxidant system against acute ethanol-induced oxidative damage in tongue tissues of rats. Wistar albino male rats, 2.5 to 3.0 months, were divided into four groups: Group I (n = 8), intact control rats; group II (n = 8), control animals given only zinc sulfate (100 mg/kg/day, for 3 consecutive days); group III (n = 14), animals given 1 mL absolute ethanol; group IV (n = 11), animals given zinc sulfate and absolute ethanol at the same dose and time. Animals were sacrificed under anesthesia 2 h after ethanol administration or 4 h after the last zinc sulfate treatment. Ethanol administration caused a marked decrease in the number of MT immunopositive cells and the proliferating cells in the lingual epithelium. A statistically significant decline in reduced glutathione levels, catalase activity and superoxide dismutase activities was also observed, whereas a significant elevation of lipid peroxidation levels and lactate dehydrogenase activities was detected in the ethanol group. In contrast, these changes were reversed by administration of zinc sulfate to ethanol-treated rats. In conclusion, it shows that zinc sulfate has therapeutic effects on acute ethanol-induced oxidative damage in the tongue tissues of rats.

Glycoprotein levels and oxidative lung injury in experimental diabetes: effect of oxovanadium(IV) complex based on thiosemicarbazone.

Diabetes mellitus (DM) is chronic and metabolic disorder, which is mainly attributed by hyperglycemia. Vanadium salts and their oxo-complexes have been shown to possess insulin-mimetic and anti-diabetic activities in animal models and diabetic patients. The main goal of this study was to investigate the protective effect of oxovanadium(IV) complex based on thiosemicarbazone (VOL) [L: (N(1)-2,4-dihydroxybenzylidene-N-(4)-2-hydroxybenzylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV)] on glycoprotein components levels and oxidative lung injury of streptozotocin (STZ)-induced diabetic rats. Male Swiss albino rats were separated into four groups. Group I (n = 5): Control (normal) animals, Group II (n = 5): Control animals administered with VOL, Group III (n = 6): STZ-induced diabetic animals, and Group IV (n = 5): STZ-induced diabetic rats treated with VOL. VOL was given to the experimental animals by gavage at a dose of 0.2 mM/kg body weight every day for 12 days. Diabetes was induced by single intraperitoneal injection of STZ (65 mg/kg body weight). On the 12th day, lung tissue samples were taken. Glycoprotein components, advanced oxidation protein products, protein carbonyl, hydroxyproline levels, and prolidase, arginase, xanthine oxidase, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and adenosine deaminase activities significantly increased whereas aryl esterase, paraoxonase-1, carbonic anhydrase, Na+/K+-ATPase activities remarkably decreased in lung tissue of diabetic rats. Treatment with VOL reversed these effects showing a beneficial effect. The present study shows that VOL has a protective effect against diabetes-induced lung damage as well as on abnormal glycoprotein component levels.

Histological and biochemical investigation of the renoprotective effects of metformin in diabetic and prostate cancer model.

BACKGROUND: Diabetes and cancer have common physiological and biochemical mechanisms. Metformin is the preferred drug of choice for the treatment of diabetes. Prostate cancer can be modeled in by injection of MAT-Lylu cells. A model of diabetes in rats is induced by streptozotocin injection. In the current study, we explored the mechanisms by which diabetes accelerates cancer, and evaluated the effects of metformin to know whether it has any impact against the damage caused by cancer and diabetic + cancer via histopathological and biochemical parameters of kidney tissue. METHODS: The experiment was carried out in rats. Groups 1-Control, 2- Diabetic, 3-Cancer, 4-Diabetic + cancer, 5-Diabetic + cancer + metformin, 6-Cancer + metformin. Metformin treatment was applied by gavage every day. The research ended on the 14th day. The collected kidney tissue sections were stained with Hematoxylin-Eosin. RESULTS: Histological evaluation showed moderate to severe damage to the kidney tissue following diabetic and cancer processess. In diabetic, cancer and diabetic + cancer groups, reduced glutathione levels, total antioxidant status, sodium/potassium-ATPase and paraoxonase1 activities were found to be significantly abated. While advanced oxidized protein products, lipid peroxidation, nitric oxide, tumor necrosis factor-alpha, reactive oxygen species levels, total oxidant status, catalase, superoxide dismutase, glutathione-related antioxidant enzymes, myeloperoxidase, and arginase activities were significantly raised. The administration of metformin reversed these defects. The outcome of the reveals that histopathological and biochemical damage in cancer and diabetes + cancer groups decreased in the groups that received metformin. CONCLUSION: In conclusion, metformin treatment can be considered an adjuvant candidate for kidney tissue in diabetes, prostate cancer and cancer therapy related damage.

Protective role of zinc in liver damage in experimental diabetes demonstrated via different biochemical parameters.

Diabetes mellitus is a serious worldwide metabolic disease, which is accompanied by hyperglycaemia and affects all organs and body system. Zinc (Zn) is a basic cofactor for many enzymes, which also plays an important role in stabilising the structure of insulin. Liver is the most important target organ after pancreas in diabetic complications. In this study, we aimed to investigate the protective role of Zn in liver damage in streptozotocin (STZ)-induced diabetes mellitus. There are four experimental groups of female Swiss albino rats: group I: control; group II: control + ZnSO4 ; group III: STZ-induced diabetic animals and group IV: STZ-diabetic + ZnSO4 . To induce diabetes, STZ was injected intraperitoneally (65 mg/kg). ZnSO4 (100 mg/kg) was given daily to groups II and IV by gavage for 60 days. At the end of the experiment, rats were killed under anaesthesia and liver tissues were collected. In the diabetic group, hexose, hexosamine, fucose, sialic acid levels, arginase, adenosine deaminase, tissue factor activities and protein carbonyl levels increased, whereas catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and Na+ /K+ -ATPase activities decreased. The administration of Zn to the diabetic group reversed all the negative effects/activities. According to these results, we can suggest that Zn has a protective role against STZ-induced diabetic liver damage.

Zinc Supplementation Restores Altered Biochemical Parameters in Stomach Tissue of STZ Diabetic Rats.

The stomach is among the organs grossly affected organ by diabetic complications. The present study was aimed at investigating the protective role of zinc on stomach of streptozotocin (STZ)-induced diabetes mellitus. Female Swiss albino rats were divided in four experimental groups: Group I, control; group II, control + zinc sulfate; group III, STZ-induced diabetic animals; and group IV, STZ-diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ, at a dose of 65 mg/kg body weight. Zinc sulfate (100 mg/kg body weight) was given daily by gavage for 60 days to groups II and IV. At the end of the experiment, the rats were sacrificed, and the tissues were taken. In the diabetic group, hexose, hexosamine, fucose, and sialic acid levels, as well as tissue factor, adenosine deaminase, carbonic anhydrase, xanthine oxidase, lactate dehydrogenase, prolidase activities, advanced oxidized protein products, homocysteine, and TNF-α levels were increased in the stomach tissue homogenates. Whereas, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, paraoxonase, and aryl esterase activities were decreased in the diabetic group. The administration of zinc reversed all the deformities. These findings suggest that zinc has protective role in ameliorating several mechanisms of STZ-induced diabetic stomach injury.

Runt-Related Transcription Factor 2 (Runx2) Is Responsible for Galectin-3 Overexpression in Human Thyroid Carcinoma.

Runx2 promotes metastatic ability of cancer cells by directly activating some of the mediators regarding malignancy. Galectin-3 (Gal-3) extensively expressed in normal and transformed cells and it is responsible for many cellular processes. In this study, we aimed to investigate whether there is any relationship between runx2 transcription factor and regulation of galectin-3 expression in different human thyroid carcinoma cell lines. To show effects of runx2 transcription factor on gal-3 expression, we developed runx2 knockdown model in the thyroid carcinoma cell lines; anaplastic 8505C and 8305C and, papillary TPC-1 and follicular FTC-133 by using siRNA transfection. We analyzed the protein expressions and mRNA levels of gal-3 and MMP2/9 in the runx2-silenced cell lines using Western blotting, qPCR, and fluorescent microscopy. Our results showed that mRNA expression levels of gal-3 and MMP2/9 were downregulated in runx2-silenced cell lines. In this investigation, we revealed that regulation of gal-3 expression was strongly correlated with runx2 transcription factor in human thyroid carcinoma. Considering the contribution of human gal-3 in collaboration with MMP2/9 to the malignant characters of many cancers, regulation of their expressions through runx2 seems like one of the key regulatory mechanism for malignant potential of human thyroid carcinoma. Accordingly, runx2 transcription factor inhibitors can be a potential target in order to prevent gal-3 mediated malignancy of human thyroid carcinoma. J. Cell. Biochem. 118: 3911-3919, 2017. © 2017 Wiley Periodicals, Inc.

Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats.

Zinc (Zn) is a component of numerous enzymes that function in a wide range of biological process, including growth, development, immunity and intermediary metabolism. Zn may play a role in chronic states such as cardiovascular disease and diabetes mellitus. Zn acts as cofactor and for many enzymes and proteins and has antioxidant, antiinflammatory and antiapoptotic effects. Taking into consideration that lung is a possible target organ for diabetic complications, the aim of this study was to investigate the protective role of zinc on the glycoprotein content and antioxidant enzyme activities of streptozotocin (STZ) induced diabetic rat tissues. Female Swiss albino rats were divided into four groups. Group I, control; Group II, control + zinc sulfate; Group III, STZ-diabetic; Group IV, diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg body weight). Zinc sulfate was given daily by gavage at a dose of 100 mg/kg body weight every day for 60 days to groups II and IV. At the last day of the experiment, rats were sacrificed, lung tissues were taken. Also, glycoprotein components, tissue factor (TF) activity, protein carbonyl (PC), advanced oxidative protein products (AOPP), hydroxyproline, and enzyme activities in lung tissues were determined. Glycoprotein components, TF activity, lipid peroxidation, non enzymatic glycation, PC, AOPP, hydroxyl proline, lactate dehydrogenase, catalase, superoxide dismutase, myeloperoxidase, xanthine oxidase, adenosine deaminase and prolidase significantly increased in lung tissues of diabetic rats. Also, glutathione levels, paraoxonase, arylesterase, carbonic anhydrase, and Na(+)/K(+)- ATPase activities were decreased. Administration of zinc significantly reversed these effects. Thus, the study indicates that zinc possesses a significantly beneficial effect on the glycoprotein components and oxidant/antioxidant enzyme activities.

Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System in Aluminum-Induced Renal Toxicity.

Aluminum has toxic potential on humans and animals when it accumulates in various tissues. It was shown in a number of studies that aluminum causes oxidative stress by free radical formation and lipid peroxidation in tissues and thus may cause damage in target organs. Although there are numerous studies investigating aluminum toxicity, biochemical mechanisms of the damage caused by aluminum have yet to be explained. Melatonin produced by pineal gland was shown to be an effective antioxidant. Since kidneys are target organs for aluminum accumulation and toxicity, we have studied the role of melatonin against aluminum-induced renal toxicity in rats. Wistar albino rats were divided into five groups. Group I served as control, and received only physiological saline; group II served as positive control for melatonin, and received ethanol and physiological saline; group III received melatonin (10 mg/kg); group IV received aluminum sulfate (5 mg/kg) and group V received aluminum sulfate and melatonin (in the same dose), injected three times a week for 1 month. Administration of aluminum caused degenerative changes in renal tissues, such as increase in metallothionein immunoreactivity and decrease in cell proliferation. Moreover, uric acid and lipid peroxidation levels and xanthine oxidase activity increased, while glutathione, catalase, superoxide dismutase, paraoxonase 1, glucose-6-phosphate dehydrogenase, and sodium potassium ATPase activities decreased. Administration of melatonin mostly prevented these symptoms. Results showed that melatonin is a potential beneficial agent for reducing damage in aluminum-induced renal toxicity.

Teduglutide, a glucagon-like peptide 2 analogue: a novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury.

Teduglutide is a long-acting synthetic analogue of human glucagon-like peptide-2 (GLP-2). GLP-2 regulates cell proliferation and apoptosis as well as normal physiology in the gastrointestinal tract. In the present study, possible cytoprotective and reparative effects of teduglutide were analyzed on a mouse model with lung injury induced by tumor necrosis factor-alpha (TNF-α) and actinomycin D (Act D). BALB/c mice were divided into six groups: control mice (I), mice injected intraperitoneally with 15 µg/kg TNF-α (II), 800 µg/kg Act D (III), Act D 2 min prior to TNF-α administration with the same doses (IV), mice injected subcutaneously with 200 µg/kg teduglutide every 12h for 10 consecutive days (V), and mice given Act D 2 min prior to TNF-α administration on day 11 after receiving teduglutide for 10 days (VI). The TNF-α/Act D administration made the lung a sensitive organ to damage. Mice lung subjected to TNF-α/Act D were characterized by the disruption of alveolar wall, induced pulmonary endothelial/epithelial cell apoptosis and expression of active caspase-3. These mice exhibited an increase in lipid peroxidation, glutathione levels, and activities of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase, as well as reduced tissue factor and sodium-potassium/ATPase activities. Teduglutide pretreatment regressed the structural damage, cell apoptosis and oxidative stress by reducing lipid peroxidation in mice received TNF-α/Act D. GLP-2 receptors were present on the cell membrane of type II pneumocytes and interstitial cells. Thus, teduglutide can be suggested as a novel protective agent, which possesses anti-apoptotic and anti-oxidant properties, against lung injury.

Z-FA.FMK activates duodenal epithelial cell proliferation through oxidative stress, NF-kappaB and IL-1beta in D-GalN/TNF-alpha-administered mice.

This study was designed to evaluate the effect of Z-FA.FMK (benzyloxycarbonyl-l-phenylalanyl-alanine-fluoromethylketone), a pharmacological inhibitor of cathepsin B, on the proliferation of duodenal mucosal epithelial cells and the cellular system that controls this mechanism in these cells in vivo. For this investigation, BALB/c male mice were divided into four groups. The first group received physiological saline, the second group was administered Z-FA.FMK, the third group received D-GalN (D-galactosamine) and TNF-alpha (tumour necrosis factor-alpha) and the fourth group was given both D-GalN/TNF-alpha and Z-FA.FMK. When D-GalN/TNF-alpha was administered alone, we observed an increase in IL-1beta-positive and active NF-kappaB-positive duodenal epithelial cells, a decrease in PCNA (proliferative cell nuclear antigen)-positive duodenal epithelial cells and an increase in degenerative changes in duodenum. On the other hand, Z-FA.FMK pretreatment inhibited all of these changes. Furthermore, lipid peroxidation, protein carbonyl and collagen levels were increased, glutathione level and superoxide dismutase activity were decreased, while there was no change in catalase activity by D-GalN/TNF-alpha injection. On the contrary, the Z-FA.FMK pretreatment before D-GalN/TNF-alpha blocked these effects. Based on these findings, we suggest that Z-FA.FMK might act as a proliferative mediator which is controlled by IL-1beta through NF-kappaB and oxidative stress in duodenal epithelial cells of D-GalN/TNF-alpha-administered mice.

Cathepsin B inhibition improves lung injury associated to D-galactosamine/tumor necrosis factor-alpha-induced liver injury in mice.

The present study was designed to investigate the effects of benzyloxicarbonyl-L-phenylalanyl-alanine-fluoromethylketone (Z-FA.FMK), an inhibitor of cathepsin B on lung injury that occurs concurrently with liver injury induced by D-galactosamine/tumor necrosis factor-alpha (D-GalN/TNF-alpha). Four groups of BALB/c male mice were treated as follows: Group 1--mice receiving intravenous (iv) injections of physiological saline; Group 2--administered with 8 mg/kg Z-FA.FMK by iv injection; Group 3--mice treated with 700 mg/kg D-GalN and 15 microg/kg TNF-alpha by sequential intraperitoneal (ip) injection; Group 4--treated with 700 mg/kg D-GalN and 15 microg/kg TNF-alpha by sequential ip injection 1 h after administration with 8 mg/kg Z-FA.FMK. Mice from Groups 3 and 4 were sacrificed 4 h after D-GalN/TNF-alpha injections. The mice treated with D-GalN/TNF-alpha showed lung damage; increased TNF receptor-associated factor immunoreactivity, lipid peroxidation, protein carbonyl content, and lactate dehydrogenase activity; decreased catalase, superoxide dismutase, and paraoxonase activities. Treatment with Z-FA.FMK resulted in an improvement of these alterations in D-GalN/TNF-alpha-administered mice. The apoptotic index of type-II pneumocytes was the almost same in the four study groups, but pneumocytes labeled with proliferating cell nuclear antigen antibody was more numerous in Group 4 mice. Our results show that D-GalN/TNF-alpha results in lung damage without induction of apoptosis. Treatment with Z-FA.FMK stimulates proliferation of type-II pneumocytes and improves degenerative alterations in injured lung occurred with liver injury induced by D-GalN/TNF-alpha.