Effects of Apixaban, Rivaroxaban, Dabigatran and Enoxaparin on Histopathology and Laboratory Parameters in Achilles Tendon Injury: An in vivo Study.

OBJECTIVES: To compare the effects of apixaban, rivaroxaban, dabigatran and enoxaparin on histopathology and blood parameters in rats with Achilles tendon injury. MATERIALS AND METHODS: Thirty adult, male Wistar albino rats weighting 220-240 g were randomly divided into five (one control and four treatment) groups and placed in a controlled environment. The Achilles tendon was incised and re-sutured in each rat, after which each group was provided the following treatment for 28 days: a) 2 ml saline to the control group, b) apixaban in 1 ml of saline (10 mg/kg/day) +1 ml of saline, c) rivaroxaban in 1 ml of saline (2 mg/kg/day) +1 ml saline, d) dabigatran in 1 ml of saline (30 mg/kg/day) +1 ml of saline, e) enoxaparin (80 µg/kg/day) + 2 ml of saline. RESULTS: Hemogram, biochemical and coagulation parameters differed significantly between the control and treatment groups (P < 0.05). Compared with the control group, in the apixaban group, type I and type III collagen immunoreactivity were severe and moderate, respectively. In the rivaroxaban and dabigatran groups, both type I and type III collagen immunoreactivity were medium and severe, respectively. In the enoxaparin group, type I and type III collagen immunoreactivity were mild and severe, respectively. CONCLUSION: The higher concentration of type I collagen in the apixaban and dabigatran indicates faster tendon healing in these groups, and the higher concentration of the type III collagen in the enoxaparin group indicates slower healing in this group.

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice.

BACKGROUND: The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. OBJECTIVES: To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. MATERIAL AND METHODS: Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively. RESULTS: The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3-1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0.1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group. CONCLUSIONS: We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.

Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-ß1 and iNOS.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson's trichrome staining. Transforming growth factor-beta 1 (TGF-ß1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1ß levels, MDA level, TGF-ß1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-ß1 and iNOS signaling pathways.

Effects of selenium, zinc, insulin and metallothionein on cadmium-induced oxidative stress and metallothionein gene expression levels in diabetic rats.

Background The aim of this study was to investigate the effects of selenium, zinc, insulin, and metallothionein on oxidative damage and metallothionein (MT) gene expression levels in streptozotocin (STZ)-induced type 1 diabetic rats exposed to Cd. Methods Rats were categorized under eight groups (control, STZ, Cd, STZ + Cd, Group 5, Group 6, Group 7, and STZ + Cd + MT [n:8/group]) were used. After diabetes was induced by STZ (55 mg/kg, i.p.), Cd was administered (1 mg/kg CdCl, orally) for 4 weeks. In cadmium-treated groups selenium (Na2SeO3 1.5 mg/kg, i.p.), zinc (ZnSO4 10 mg/kg via oral gavage), insulin (insulin glargine, 2U/day, s.c.), and MT (1mg/kg, every other 10 days, s.c.) were administered. MT gene expression levels, MDA levels, GPx, SOD, and CAT activity levels were determined in liver and kidney tissues. Results MT gene expression and MDA levels increased (p < 0.05) while GPx and SOD activity levels decreased (p < 0.05) in STZ, Cd, and STZ + Cd groups. In Group 5, Group 6, Group 7, and Group 8 groups MT gene expression and MDA levels were decreased while GPx and SOD activity levels were increased (p < 0.05). CAT activity significantly increased (p < 0.05) in STZ + Cd group while there were no significance in other groups (p > 0.05). Compared to the control, Group 5, Group 6, Group 7, and Group 8 groups provided no difference for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine levels (p > 0.05). Conclusions Our results suggest that Se, insulin, Zn and MT may have protective effects against hepatotoxicity and nephrotoxicity caused by Cd exposure in diabetic rats by reducing oxidative stress and MT gene expression levels.

The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats.

The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-α and IL-1ß levels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson's trichrome, and 0.1% toluidine blue. TNF-α, IL-1ß, and MDA levels and hydroxyproline content significantly increased (p < 0.01) and GPx and SOD activities significantly decreased in bleomycin group (p < 0.01). Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-α and IL-1ß activity, hydroxyproline content, and MDA level (p < 0.01) and increased GPx and SOD activities (p < 0.05). Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis.

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice.

CONTEXT: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet. OBJECTIVE: The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice. MATERIALS AND METHODS: Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver. RESULTS: In extract, vanillic (632.093 µg/g) and chlorogenic acids (555.0 µg/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p < 0.01), increased memory retention (p < 0.01), reduced MDA levels (p < 0.05), and elevated SOD, GPx, and CAT activities (p < 0.05) compared with the d-galactose group. DISCUSSION AND CONCLUSION: These results show that M. nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.

Effect of Capparis spinosa L. on cognitive impairment induced by D-galactose in mice via inhibition of oxidative stress.

BACKGROUND/AIM: To determine the phenolic acid levels and DNA damage protection potential of Capparis spinosa L. seed extract and to investigate the effect of the extract on cognitive impairment and oxidative stress in an Alzheimer disease mice model. MATERIALS AND METHODS: Thirty BALB/c mice divided into 5 groups (control, D-galactose, D-galactose + C. spinosa 50, D-galactose + C. spinosa 100, D-galactose + C. spinosa 200) were used. Mice were administered an injection of D-galactose (100 mg/kg, subcutaneous) and orally administered C. spinosa (50, 100, or 200 mg/kg) daily for 8 weeks. RESULTS: Syringic acid was detected and the total amount was 204.629 µg/g. Addition of 0.05 mg/mL C. spinosa extract provided significant protection against the damage of DNA bands. C. spinosa attenuated D-galactose-induced learning dysfunctions in mice and significantly increased memory retention. Malondialdehyde (MDA) levels increased and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities decreased in the D-galactose group. C. spinosa (200 mg/kg body weight) significantly decreased MDA level and increased SOD, GPx, and CAT activities. CONCLUSION: These results show that C. spinosa has the potential in ameliorating cognitive deficits induced by D-galactose in mice and the antioxidant activity may partially account for the improvement of learning and memory function.

The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats.

In this study, octreotide (OCT), a synthetic somatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 µg/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect.

Effect of 3-(1H-Pyrrol-2-yl)-1H-indazole on the antioxidant status of rats.

The influence of injection periods of 3-(1H-pyrrol-2-yl)-1H-indazole regarding vitamins A, E, C, selenium (Se), malondialdehyde (MDA) levels, and glutathione peroxidase (GSH-Px) activity in rats has been investigated. The substance was given by subcutaneous injection at 20 mg/kg every other day for a total of 15 injections. At the end of the treatment, Se levels in serum were determined by fluorimetry, and those of vitamins A, E, C, and malondialdehyde in serum, liver, and kidney were determined by high-performance liquid chromatography. GSH-Px activities in erythrocytes were determined spectrophotometrically. Vitamins A, E, C, and Se levels were generally lower than in the controls, while GSH-Px activity at the third injection period was maximally increased, with the activities after the other injection periods being higher than in the control group. In addition, vitamins A, E, and C levels were generally lower than the control groups, while serum, liver, and kidney MDA levels gradually increased depending on injection periods. On the other hand, GSH-Px activity was higher than in the control group. Thus, the results show that while vitamins A, E, C, and Se levels decreased, MDA levels and GSH-Px activities increased after administration of 3-(1H-pyrrol-2-yl)-1H-indazole to the rats. These findings might be related to the increased amount of free radicals caused by 3-(1H-pyrrol-2-yl)-1H-indazole injection.

Protective effect of octreotide on intra-tracheal bleomycin-induced oxidative damage in rats.

The present study is aimed at determining the effect of parenteral octreotide against oxidative damage caused by intra-tracheal bleomycin (BLM) administration. A total of 30 male Wistar rats randomly divided into three groups (control, bleomycin alone, and bleomycin and octreotide) were used in the study. A group of animals received a single dose of intra-tracheal bleomycin (7.5mg/kg). Animals in another group, which also received intra-tracheal bleomycin, were given 82.5 microg/kg octreotide via i.m. injection for a week. Animals in the control group received neither bleomycin nor octreotide. All animals were sacrificed at the end of the experiment. Serum levels of malondialdehyde, vitamins A, E, and C, selenium levels were determined. In addition, glutathion peroxidase activity levels in erythrocytes were also determined. Malondialdehyde levels and glutathion peroxidase activity were increased whereas antioxidant vitamin levels were decreased significantly in animals that received only bleomycin compared to control animals (p<0.05). The values in rats that received bleomycin and octreotide were found to be closer to the control group (p<0.05). Selenium levels in animals that received only bleomycin were determined to be reduced compared to controls (p<0.05). On the other hand, selenium levels in bleomycin and octreotide groups were similar to control values in (p<0.05). In conclusion, bleomycin induces a severe stress and more importantly increases the amount of free radicals whereas octreotide administration reduces this oxidative damage significantly.

Investigation of oxidative status of the 2-furan-2-yl-1H-benzimidazole in rats.

We investigated the influence of 2-furan-2-yl-1H-benzimidazole regarding vitamins A, E, C, selenium (Se), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels on rats. 2-Furan-2-yl-1H-benzimidazole was given to rats by subcutaneous injection every other day for a total of 22 injections. At the end of the experiment, Se levels were determined by using a fluorimetric method. Serum levels of vitamins A, E, C, and malondialdehyde (MDA) were determined by high-performance liquid chromatography. Glutathione peroxidase (GSH-Px) levels of erythrocytes were spectrophotometrically determined. Our experimental results showed that vitamins A, E, C, and Se levels were found generally lower than the control groups, while serum MDA level and GSH-Px activity flexibly increased, which is dependent on injection days. The observed decreases in vitamins A, E, C, and Se levels in the blood might be causally related to the increased amount of free radicals that are generated with 2-furan-2-yl-1H-benzimidazole injection. However, further investigations are needed to clarify the significance of this observation in respect with the 2-furan-2-yl-1H-benzimidazole injection.

Effects of selenium with vitamin E and melatonin on cadmium-induced oxidative damage in rat liver and kidneys.

The present study was performed to determine the protective effects of melatonin alone and vitamin E with selenium combination against cadmium-induced oxidative damage in rat liver. A total of 60 male rats were equally divided into five groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the four group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and liver and kidneys were excised for histopathological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of superoxide dismutase (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to nontreated animals (p < 0.05) and increase in the enzyme activity that was almost the same as the controls. The pathological findings were also in parallel with the results of the biochemical analysis. In conclusion, all the agents tested had protective effects against cadmium-induced oxidative damage.

Ultrastructural changes in the kidney of rats with acute exposure to cadmium and effects of exogenous metallothionein.

Ultrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT) were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride (CdCl2) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 micromol/kg MT was administered in addition to CdCl2. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7 after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic observations. Tissue damage in kidney increased as time passed since the administration of CdCl2 in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules, deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted, and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused structural damage. Exogenous MT partly prevents CdCl2-induced damage.

Protective effects of antioxidants against cadmium-induced oxidative damage in rat testes.

The protective effects of melatonin, vitamin E, and selenium alone or in combination were tested against cadmium-induced oxidative damage in rat testes. A total of 60 male rats were equally divided into five study groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the fourth group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and the testes were excised for histological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of the enzyme (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to the nontreated animals (p < 0.05) and an increase in the superoxide dismutase activity that was almost the same as the controls. The combination of melatonin, vitamin E, and selenium appears to have the more profound effect against cadmium-induced testicular injury.

Effects of selenium and vitamin E, in addition to melatonin, against oxidative stress caused by cadmium in rats.

The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination against high dose cadmium-induced oxidative stress in rats. The control group received subcutaneous physiological saline. The first study group administered cadmium chloride (CdCl2) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth study group administered CdCl2 plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl2 administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl2 administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl2 received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective effects against high dose cadmium-induced oxidative damage.

Synthesis and oxidant properties of novel (5-bromobenzofuran-2-yl)(3-methyl-3-mesitylcyclobutyl)ketonethiosemicarbazone.

The reaction of 5-bromosalicylaldehyde with 1-mesityl-1-methyl-3-(2-chloro-1-oxoethyl)cyclobutane (1) and potassium carbonate was used to prepare (5-bromobenzofuran-2-yl)(3-methyl-3-mesitylcyclobutyl)methanone (2) for the starting reagent purposes. (5-Bromobenzofuran-2-yl)(3-methyl-3-mesitylcyclobutyl)ketonethiosemicarbazone (3) was synthesized from the reaction of the compound (2) with thiosemicarbazide. In the present study, it was aimed to examine the influence of synthetic (5-bromobenzofuran-2-yl)(3-methyl-3-mesityl cyclobutyl)ketonethiosemicarbazone on levels of vitamins (A, E, C), selenium and malondialdehyde in rats. A total of 42 rats were used and the animals were divided into two groups in the study. Only a subcutaneous injection of 250 microl of 75% ethanol was given to the control group every other day. A subcutaneous injection of this compound (25 mg kg-1, dissolved in 250 microl of 75% ethanol) was administered to the other group of rats. After the application of (5-bromobenzofuran-2-yl)(3-methyl-3-mesitylcyclobutyl)ketonethiosemicarbazone for 20 days, the serum vitamins (A, E, C) and malondialdehyde levels were determined with high performance liquid chromatography, the serum selenium level was determined by using fluorescence spectrophotometer. The serum vitamin A, E, C and selenium levels were significantly decreased compared to control group (P<0.005), whereas serum malondialdehyde levels were higher than control group levels (P<0.005). As a result, it could be suggested that this compound induced a severe stress, and also increased the amount of free radicals depending on the stress.

Effects of exogenous metallothionein on acute cadmium toxicity in rats.

The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) to rats exposed to high cadmium levels. A total of 72 rats were used in the study. The animals were divided into three groups: controls, Cd administered, and Cd+MT. Cadmium was administered by subcutaneous injection of cadmium(II) chloride at a dose of 3.5 mg/kg for 7 d. In addition to CdCl2, 30 micromol/kg MT was administered to the second group of rats (group II). Control rats received 0.5 mL physiologic serum via subcutaneous injection. Eight rats from each group were sacrificed on the 1st, 3rd, 5th, and 7th day after administration of the compounds. Liver, kidney, and blood samples were harvested. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), serum ALT, AST, BUN, ALP, creatinine, and urea were measured. MDA levels in group I were observed to increase starting from d 1 compared to group II (p<0.05). Although MDA levels in group II were higher than controls (p<0.05), they were lower, especially in liver and blood, compared to group II. Erythrocyte GSH-Px activity levels were determined to decrease starting from d 1 in both groups (p<0.05). Decreases in GSH-Px activity levels in group II were less than group I. Serum creatinine levels in both groups were increased significantly compared to controls (p<0.05); the increase in group I was higher than group II. Serum ALT, AST, and ALP levels in group I increased to very high levels compared to controls, whereas increases in group II were at moderate levels (p<0.05). Although serum BUN levels were determined to be reduced, there was no significant change among the groups. Serum urea levels in both groups were higher than controls. Based on our results, it is possible to postulate that exogenous MT can act as antioxidant against Cd toxicity and lipid peroxidation.