Antioxidant Activity and Protective Effects of an Oxovanadium (IV) Complex on Heart and Aorta Injury of STZ-Diabetic Rats.

Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings.

Protective effects of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium (IV) on oxidative brain injury in streptozotocin-induced diabetic rats.

Diabetes is usually accompanied by increased production of free radicals or impaired antioxidant defenses. The brain is a target tissue of the oxidative attacks caused by diabetes, and there are observed changes in the biochemical parameters of this tissue in the hyperglycemic state. In this study, we aimed to show the effect of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium (IV) (VOL) compound on diabetic damaged brain tissue, induced by streptozotocin (STZ) on 3.0-3.5-month-old male rats. Single dose of STZ at 65 mg/kg was used to make rats diabetic. Four groups were created randomly. Group (i): control (intact) animals; Group (ii): VOL given control animals; Group (iii): STZ-induced diabetic animals; and Group (iv): orally VOL administered STZ-induced diabetic rats. VOL (0.2 mM/kg/day) administration to control and diabetic animals was performed for a period of 12 days. At the end of day 12, the brain tissues were taken and homogenized. The clear supernatants were used for the determination of glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG), and protein levels. Alanine and aspartate transaminases and acetylcholinesterase (AChE), myeloperoxidase (MPO), xanthine oxidase (XO), and oxidative stress marker enzymes activities were also estimated from the homogenates. According to the obtained results, there is found significant elevation of MDA and NEG levels and activities of transaminases, MPO and XO; whereas the GSH content and the activities of AChE and antioxidant enzymes were strongly decreased in the STZ-induced diabetic brain tissues in comparison to control group animals. Twelve days of administration of VOL complex to the diabetic animals reversed all biochemical parameters significantly in diabetic brain tissues. Our findings suggest that the VOL complex may be an ideal candidate to be used as an anti diabetic agent to improve oxidative injury and protect the brain tissue against damage caused by diabetes. This healing effect of the VOL complex may be due to its antioxidant activity and the insulin-mimetic effects of vanadium.

Vitamin U prevents valproic acid-induced liver injury through supporting enzymatic antioxidant system and increasing hepatocyte proliferation triggered by inflammation and apoptosis.

The aim of this study was to investigate the cellular mechanisms that cause valproic acid (VPA)-induced liver damage and the therapeutic effect of Vitamin U (Vit U) on these mechanisms. Female Sprague Dawley rats were randomly divided into four groups: intact control animals, animals that received Vit U (50 mg/kg/day), animals given VPA (500 mg/kg/day), and animals given both VPA and Vit U. The rats in the Vit U + VPA group were administered Vit U by gavage an hour before VPA administration every day for 15 days. Liver tissues were evaluated through histopathological, biochemical, immunohistochemical, and Western blotting techniques. Administration of Vit U with VPA resulted in (i) prevention of histopathological changes caused by VPA; (ii) blockage of the decrease in catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities; prevention of the elevation in gamma-glutamyl transferase (GGT) activity and advanced oxidation protein products (AOPP) level; (iii) increased in the levels of interleukin-1 beta (IL-1ß), active caspase-3, and cytoplasmic cytochrome c; (iv) increase in cleaved poly (ADP-ribose) polymerase (PARP) level and decrease in LC3B (II/I) ratio; (v) increase in the number of proliferating cells nuclear antigen (PCNA) positive hepatocytes. These findings show that Vit U prevents liver damage caused by VPA through increasing the antioxidant enzyme capacity and hepatocyte proliferation by triggering inflammation and apoptosis. These findings suggest that Vit U provides its protective effects against VPA-induced liver damage by stimulating homeostasis and regeneration.

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.

Protective Effects of an Oxovanadium(IV) Complex with N2O2 Chelating Thiosemicarbazone on Small Intestine Injury of STZ-Diabetic Rats.

Vanadium compounds are being investigated as potential therapeutic agents in the treatment of many health problems, primarily diabetes. We aimed to provide the effect of N(1)-4-hydroxysalicylidene-N(4)-salicylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV) (VOL) on small intestinal injury in experimental male diabetic rats. Four groups were created of 3.0-3.5-month-old rats. The rats were made diabetic by a single dose of streptozotocin (STZ) at 65 mg/kg and grouped as follows: control animals, VOL-given control animals, STZ-induced diabetic animals and STZ-induced diabetic animals given VOL. A daily dose of 0.2 mM/kg vanadium complex was administered orally for 12 days after the inducement of diabetes. On the 12th day, small intestine tissue samples were taken. According to the data obtained from the biochemical analysis, reduced glutathione (GSH) level, catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), Na+/K+-ATPase and paraoxanase (PON) activities were increased, whereas sialic acid (SA), xanthine oxidase (XO) and disaccharidases (maltase and saccharidase) activities were decreased in the small intestine tissue of VOL-treated diabetic rats. Microscopic examinations revealed a remarkable decrease in the mucosal necrotic areas, discontinuity in the brush border, deterioration of the villi integrity and oedema inside the villi, but with a mild decrease in the inflammatory cells, deterioration and loss of integrity of the gland in the small intestine of VOL-treated diabetic rats. Moreover, VOL treatment markedly decreased the proliferation of villus cells and especially inflammatory cells in the small intestine of diabetic rats. According to the obtained data, the administration of VOL is a potentially convenient strategy to reducing small intestine injury in diabetic rats.

The protective effect of vitamin U on valproic acid-induced lung toxicity in rats via amelioration of oxidative stress.

Vitamin U (Vit U) is a novel free-radical scavenger. The protective effect of Vit U on valproic acid (VPA)-induced lung damage was examined. Rats were divided into four groups: control rats; rats given Vit U (50 mg/kg/d, by gavage) for 15 days; rats treated with VPA (500 mg/kg/d, intraperitoneally) for 15 days; and rats were given VPA + Vit U (in same dose and time). On the 16th day of the experiment, the lungs were collected from rats. Lung structure, pulmonary oxidant/antioxidant parameters and Nrf2, α-SMA, and collagen-1 were evaluated by microscopic and biochemical analysis. Additionally, it was determined the interactions of Vit U with Nrf2 and Keap1 by in silico analysis. VPA administration increased lipid peroxidation and the activity of lactate dehydrogenase and myeloperoxidase. However, it decreased the glutathione level, and the activities of glutathione peroxidase, glutathione-S-transferase, catalase, and superoxide dismutase. VPA-mediated oxidative stress prompted structural distortion and fibrotic alterations in the lung. Vit U supplementation reversed structural and biochemical alterations, induced antioxidant system through Nrf2 activation, and attenuated fibrosis by reducing collagen expression in VPA-administered rats. However, Vit U pretreatment was unable to reduce α-SMA levels in the lung of VPA-treated rats. Molecular docking analysis showed the binding of Vit U to ETGE motif leads to dissociation of Nrf2 from the Nrf2/Keap1 complex and its transfer to nuclei. In conclusion, Vit U attenuated VPA-induced tissue damage by restoring antioxidative systems through amelioration of Nrf2 activity in the lung under oxidative stress.

The effects of chard on brain damage in valproic acid-induced toxicity.

Valproic acid (VPA; 2-propyl valeric acid) is a potent drug widely used in treating anxiety disorders, migraine as well as epileptic diseases. In the ongoing study chard protective effect was investigated, on the damaged VPA rat brain. Sprague Dawley rats (females) were grouped as follows: control, VPA (500 mg kg-1  day-1 VPA intraperitoneal), chard (100 mg/kg day chard extract by gavage), VPA + chard (500 mg kg-1  day-1 VPA + 100 mg kg-1  day-1 chard extract). Aqueous chard leaves extract was given 1 hr before apply VPA for a period of 7 days. Lipid peroxidation, advanced oxidation protein products and protein carbonyl content, and superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase activities increased in the VPA group. Reduced glutathione levels, paraoxanase, and acetylcholinesterase activities were significantly diminished in the VPA animals. Chard extract application curatively reverted the studied biochemical parameters. The results obtained, it has been found the chard has a protective and antioxidant effect on brain damage induced by VPA. PRACTICAL APPLICATIONS: Valproic acid is a comparably safe pharmaceutical agent, but it can cause severe adverse effects on biological metabolism when it is used in high amount. There are not many studies declared that VPA stimulate the generation of ROS, which is liable for the life-threatening adverse effects of VPA therapy including hepatotoxicity neurotoxicity and teratogenicity. Chard is a plant which has antimicrobial, antibacterial, antiinflammatory, antioxidant, antitumor, antiacetylcholinesterase activities, and hepatoprotective effects. In the current study we examined the protection of the VPA damaged rat brain by chard.

The effects of vitamins and selenium mixture against brain tissue induced by d-galactosamine.

Brain damage is a major complication of fulminant hepatic failure. d-Galactosamine (d-GalN)-induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d-GalN stimulated brain injury were investigated in this study. Sprague-Dawley female rats aged 2.0-2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg-1 ·day-1 vitamin C, 15 mg·kg-1 ·day-1 of ß-carotene, 100 mg·kg-1 ·day-1 of α-tocopherol in addition to 0.2 mg·kg-1 ·day-1 of sodium selenate for 3 days. The third group was given a single dose of d-GalN hydrochloride at the concentration of 500 mg·kg-1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d-GalN. Tissue samples were collected under ether anesthesia. The rats treated with d-GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione-S-transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d-GalN.

Effects of edaravone on cardiac damage in valproic acid induced toxicity.

OBJECTIVES: An increasing number of studies have pointed out the side effects of valproic acid (VPA), an antiepileptic drug used for the treatment of seizures in children and adults. The aim of this study is to evaluate whether VPA interferes with oxidative metabolism in the heart and whether edaravone, the novel free radical scavenger, ameliorates any such effects. METHODS: Female rats were divided into four groups: intact control animals, VPA (0.5 g/kg/day), edaravone (30 mg/kg/day), and VPA+edaravone (0.5 g/kg/day+30 mg/kg/day) injected groups for seven days. On the 8(th) day the animals were sacrificed under ether anesthesia, and hearts were homogenized. Concentrations of malondialdehyde (MDA), sialic acid (SA), glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione -S- transferase (GST), glutathione peroxidase (GPx), myeloperoxidase (MPO), Na+K+ ATPase and tissue factor (TF) were evaluated in the homogenates. KEY FINDINGS: In the VPA group, increased MDA levels and decreased GPx activities indicated heart damage compared with the control group. On the other hand, edaravone treatment in the VPA group increased the activities of GST and SOD and decreased the activities of TF and ALP. CONCLUSIONS: Our study is the first to demonstrate the beneficial effects of edaravone on the impaired oxidant/antioxidant status of heart in VPA-induced toxicity.

Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats.

Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.

Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats.

In this study, we aimed to investigate the effects of vitamin U (Vit U) on valproic acid (VPA)-induced liver damage. Female Sprague Dawley rats were randomly divided into four groups. Group I was intact control animals. Group II was control rats given Vit U (50 mg/kg/day) for fifteen days. Group III was given only VPA (500 mg/kg/day) for fifteen days. Group IV was given VPA+Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals were fasted overnight and then sacrificed under ether anesthesia. Liver tissue was taken from animals, homogenized in 0.9% saline to make up to 10% homogenate. Liver aspartate and alanine transaminases, alkaline phosphatase, lactate dehydrogenase, myeloperoxidase, sorbitol dehydrogenase, glutamate dehydrogenase and xanthine oxidase activities and lipid peroxidation levels were increased and paraoxonase activity and glutathione levels were decreased in VPA group. Treatment with Vit U reversed these effects. These results demonstrated that administration of Vit U is a potentially beneficial agent to reduce the liver damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.

Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats.

In recent years, the role of free radical damage consequent to oxidative stress is widely discussed in diabetic complications. In this aspect, the protection of cell integrity by trace elements is a topic to be investigated. Vanadium is a trace element believed to be important for normal cell function and development. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the muscle tissue of diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) to male Swiss albino rats. The rats were randomly divided into 4 groups: Group I, control; Group II, vanadyl sulfate control; Group III, STZ-diabetic untreated; Group IV, STZ-diabetic treated with vanadyl sulfate. Vanadyl sulfate (100 mg/kg) was given daily by gavage for 60 days. At the last day of the experiment, rats were killed, muscle tissues were taken, homogenized in cold saline to make a 10% (w/v) homogenate. Body weights and blood glucose levels were estimated at 0, 30 and 60th days. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), as well as carbonic anhydrase (CA), myeloperoxidase (MPO) activities and protein carbonyl content (PCC) were determined in muscle tissue. Vanadyl sulfate administration improved the loss in body weight due to STZ-induced diabetes and decreased the rise in blood glucose levels. It was shown that vanadium supplementation to diabetic rats significantly decrease serum antioxidant enzyme levels, which were significantly raised by diabetes in muscle tissue showing that this trace element could be used as preventive for diabetic complications.

Synthesis, characterization and antidiabetic properties of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium(IV).

A new oxovanadium(IV) chelate [VOL] (L: N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato) was synthesized and characterized by elemental analysis, conductivity and magnetic measurements, UV-vis, IR, EPR spectroscopy and mass spectrometry. The biochemical and immunohistochemical effects of the administration of the vanadium complex (VOL) into the pancreas of normal and streptozotocin-induced diabetic rats were profoundly investigated. The animals were randomly divided into four groups. Group I: control (intact) animals. Group II: control animals administered with VOL. Group III: STZ-induced diabetic animals. Group IV: STZ-induced diabetic animals administered with VOL. VOL was given to some of the experimental animals by gavage at a dose of 0.2mM/kg every day for 12 days. Blood samples were collected from animals, on 0 and 1, 6 and 12 days after STZ injection. On day 12, the pancreatic tissues were taken from the animals. The tissue sections were labelled with streptavidin biotin peroxidase technique for insulin. In the diabetic group, the blood glucose levels, aspartate and alanine transaminases, alkaline phosphatase activities were increased. But, in the diabetic+VOL groups, the blood glucose levels, aspartate and alanine transaminases, alkaline phosphatase activities were reduced. In the diabetic group, a decrease in the pancreatic glutathione levels, glutathione peroxidase and superoxide dismutase activities and an increase in the pancreatic lipid peroxidation level and catalase activities were observed. The administration of VOL to the diabetic rats reversed this diabetic effect due to its insulinomimetic effects. According to the immunohistochemical and biochemical results obtained, it was concluded that VOL can regenerate B cells of the pancreas in experimental diabetes and has an antidiabetic and protective effects on the pancreas.

Effects of Z-FA.FMK on D-galactosamine/tumor necrosis factor-alpha-induced kidney injury and oxidative stress in mice : effects of Z-FA.FMK on TNF-alpha-mediated kidney injury.

BACKGROUND: The aim of this investigation was to demonstrate that benzyloxicarbonyl-L-phenylalanyl-alanine-fluoromethylketone (Z-FA.FMK), which is a pharmacological inhibitor of cathepsin B, has protective role on the kidney injury that occurs together with liver injury. Methods BALB/c male mice used in this study were divided into four groups. The first group was given physiologic saline only, the second group was administered Z-FA.FMK alone, the third group received D: -galactosamine and tumor necrosis factor-alpha (D-GalN/TNF-alpha), and the fourth group was given both D-GalN/TNF-alpha and Z-FA.FMK. One hour after administration of 8 mg/kg Z-FA.FMK by intravenous injection, D-GalN (700 mg/kg) and TNF-alpha (15 microg/kg) were given by intraperitoneal injection. Results In the group given D-GalN/TNF-alpha, the following results were found: severe degenerative morphological changes in the kidney tissue, a significant increase in the number of activated caspase-3-positive tubular epithelial cell, an insignificant increase in the number of proliferating cell nuclear antigen (PCNA)-positive tubular epithelial cell, a decrease in the kidney glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, an increase in the kidney lipid peroxidation (LPO) levels, lactate dehydrogenase (LDH) activity, serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities, uric acid and urea levels. In contrast, in the group given D-GalN/TNF-alpha and Z-FA.FMK, a significant decrease in the D-GalN/TNF-alpha-induced degenerative changes, a decrease in the number of activated caspase-3-positive tubular epithelial cell, a insignificant decrease in the number of PCNA-positive tubular epithelial cell, an increase in the kidney GSH levels, CAT, SOD and GPx activities, a decrease in the kidney LPO levels, LDH activity, serum AST and ALT activities, uric acid and urea levels were determined. Conclusion These results suggest that pretreatment with Z-FA.FMK markedly lessens the degree of impairment seen in D-GalN/TNF-alpha-induced kidney injury, which occurred together with liver injury in mice.

The effects of combined alpha-tocopherol, ascorbic acid, and selenium against cadmium toxicity in rat intestine.

In this study, the effects of combined antioxidants treatment against cadmium toxicity were investigated microscopically, immunohistochemically, and biochemically in small intestine of Sprague Dawley rats. The rats were subdivided into four groups as intact control, cadmium was administrated, and both control and cadmium groups treated with ascorbic acid, alpha-tocopherol, and selenium. Metallothionein expression was localized in the base of intestinal glands in control rats and similar expression was observed with antioxidants treatment. In cadmium-administrated rats, metallothionein expression was detected in surface epithelium, longitudinal muscle layer, meissner, and myenteric plexuses, but not in the base of intestinal gland. On the other hand, in the rats treated with antioxidants and cadmium, immunreactivity increased in the surface epithelium and in the base of intestinal glands according to cadmium-administrated rats but not changed in the plexuses and longitudinal muscle layer. Biochemically, lipid peroxidation levels increased and glutathione levels decreased significantly in intestine of the cadmium group compared to the control. Treatment with antioxidants in cadmium-administrated rats led to a decrease in lipid peroxidation levels and a significant increase in glutathione levels. As a result, the combination of ascorbic acid, alpha-tocopherol, and selenium shows a protective effect against cadmium toxicity in small intestine.

Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta.

The aim of this study was to investigate the protective effects of vanadyl sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals.

The potential role of combined anti-oxidants against cadmium toxicity on liver of rats.

Cadmium (Cd), a widely distributed toxic trace metal, has been shown to accumulate in liver after long- and short-term exposure. Cd (2 mg/kg/day CdCl2) was intraperitoneally given to rats for eight days. Vitamin C (250 mg/kg/day) + vitamin E (250 mg/kg/day) + sodium selenate (0.25 mg/kg/day) were given to rats by oral means. The animals were treated by anti-oxidants one hour prior to treatment with Cd every day. The degenerative changes were observed in the groups given only Cd and anti-oxidants + Cd. Metallothionein (MT) immunoreactivity increased in cytoplasm of hepatocytes of the rats given Cd when compared with controls. In a number of cells with Cd and anti-oxidants treatment, immunoreactivity increase was more than in the group given Cd only and nuclear MT expression was also detected. Cell proliferation was assessed with proliferating cell nuclear antigen (PCNA) immunohistochemistry. PCNA expressions increased in all groups more than in the controls. Anti-oxidants treatment increased cell proliferation. In the animals administered with Cd, an increase in serum aspartate (AST) and alanine (ALT) aminotransferases, liver glutathione (GSH) and lipid peroxidation (LPO) levels were observed. On the other hand, in the rats treated with anti-oxidants and Cd, serum AST and ALT, liver glutathione and LPO levels decreased. As a result, these results suggest that combined anti-oxidants treatment might be useful in protection of liver against Cd toxicity.

Influence of zinc sulfate intake on acute ethanol-induced liver injury in rats.

AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury. METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group II; control rats given only zinc, group III; animals given absolute ethanol, group IV; rats given zinc and absolute ethanol. Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol. RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione. CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate.

Vanadyl sulfate administration protects the streptozotocin-induced oxidative damage to brain tissue in rats.

Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multifactorial. The present study was carried out to investigate the effects of vanadyl sulfate on biochemical parameters, enzyme activities and brain lipid peroxidation, glutathione and nonenzymatic glycosylation of normal- and streptozotocin-diabetic rats. Streptozotocin (STZ) was administered as a single dose (65 mg/kg) to induce diabetes. A dose of 100 mg/kg vanadyl sulfate was orally administered daily to STZ-diabetic and normal rats, separately until the end of the experiment, at day 60. In STZ-diabetic group, blood glucose, serum sialic and uric acid levels, serum catalase (CAT) and lactate dehydrogenase (LDH) activities, brain lipid peroxidation (LPO) and nonenzymatic glycosylation (NEG) increased, while brain glutathione (GSH) level and body weight decreased. In the diabetic group given vanadyl sulfate, blood glucose, serum sialic and uric acid levels, serum CAT and LDH activities and brain LPO and NEG levels decreased, but brain GSH and body weight increased. The present study showed that vanadyl sulfate exerted antioxidant effects and consequently may prevent brain damage caused by streptozotocin-induced diabetes.