Protective agent, erdosteine, against cisplatin-induced hepatic oxidant injury in rats

Cisplatin, one of the most active cytotoxic agents against cancer, has several toxicities. Hepatotoxicity is one of them occurred during high doses treatment. The aim of this study was to determine the effects of erdosteine against cisplatin-induced liver injury through tissue oxidant/antioxidant parameters and light microscopic evaluation. The rats were randomly divided into three groups: control (n=5), cisplatin (10 mg/kg, n=6) and cisplatin+erdosteine (50 mg/kg/day oral erdosteine, n=8) groups. The rats were sacrificed at the 5th day of cisplatin treatment. The liver tissues were examined with light microscopy and oxidant/antioxidant biochemical parameters. The malondialdehyde (MDA) and nitric oxide (NO) levels were increased in the cisplatin group in comparison with the control and cisplatin+erdosteine groups (p<0.05). There was no significant difference in MDA and NO levels between control and cisplatin+erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in cisplatin+erdosteine group than cisplatin group (p<0.05). However, the CAT and GSH-Px activities were significantly lower in cisplatin group than in control group (p<0.05). The light microscopic examination revealed that cytoplasmic changes especially around cells of central vein were observed in cisplatin group. Hepatocellular vacuolization was seen in these cells. In the cisplatin plus erdosteine group, a decrease in cytoplasmic changes with the hepatocytes and sinusoidal dilatations around cells of central vein were noticed in as compared to cisplatin group. In the light of microscopic and biochemical results, it was concluded that cisplatin-induced liver damage in high dose and erdosteine prevented this toxic side effect by the way of its antioxidant and radical scavenging effects. (Mol Cell Biochem 278: 79–84, 2005)     

Effects of repeated desflurane and sevoflurane anesthesia on enzymatic free radical scavanger system

Background: To investigate the possible effects of repeated sevoflurane and desflurane anesthesia on hepatocellular system by evaluating the free radical metabolism, hepatocellular enzymes and histopatholgical changes in rats. Methods: Four groups of animals were studied. Sevoflurane 2% (v/v) and desflurane 6% (v/v) in air/O₂ were administered to animals in group II (n = 9) and III (n = 9) respectively. 100% (v/v) O₂ was administered in group IV (n = 9). Administration was done for 60 minutes over 3 days. Nine animals were allocated to control group (group I), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), glutathione-s-transferase (GST) and thiobarbituric acid reactive substances (TBARS) were studied. Also electron microscopy was performed. Results: Catalase, SOD, GSH-Px, GST activities and TBARS levels were significantly higher in groups II and III than in group I (p < 0.05). All parameters were significantly higher in groups II versus group IV (p < 0.05). On the other hand, SOD, GSH-Px and GST activities were significantly elevated in group III than IV, but CAT activity and TBARS levels were not significantly. Catalase, SOD, GSH-Px, GST but not TBARS levels were significantly higher in groups II and III than in group IV (p < 0.05). TBARS levels were higher in group III than in group IV, but this elevation was not statistically significant. CAT, SOD and GSH-Px activities were significantly higher in groups II than in group III (p < 0.05). Conclusion: Although electron microscopy findings were similar for group II and III, we can conclude that sevoflurane might cause more cellular damage than desflurane by causing higher activation of free radical metabolising enzymes.     

Effects of Selenium and Vitamin E,in Addıtıon 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 subcutanous 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.     

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 μmol/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.     

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL.     

Protective effects of ascorbic acid on hepatotoxicity and oxidative stress caused by carbon tetrachloride in the liver of Wistar rats

This study was planned to investigate the protective effect of l (+)‐ascorbic acid (Vit C) on CCl₄‐induced hepatotoxicity and oxidative stress in the liver of Wistar rats (Rattus Norvegicus, strain Wistar). Twenty‐four adult male Wistar rats were fed with standard rat chow diet for 10 days and randomly were divided into four groups of six each as follows: (1) control, (2) CCl₄, (3) “CCl₄ + Vit C”, (4) Vit C groups. CCl₄ was applied to rats belonging to CCl₄ and “CCl₄ + Vit C” groups subcutaneously at 1 mg kg^?1 dose CCl₄ for 3 days. Vit C applied to “CCl₄ + Vit C” and “Vit C” group rats intraperitoneally at 300 mg kg^?1 dose for 3 days. All rats were sacrificed and livers were quickly removed on the fourth day of the experiment. MDA, total glutathione (T.GSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐PX) activities were measured in the liver of all groups of rats and also serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were detected to determine liver functions in all groups of rats. Histopathological changes were evaluated by light and transmission electron microscopes. In “CCl₄ + Vit C” group, MDA level was significantly decreased (p < 0.05) and SOD, CAT, GSH‐PX activities were significantly increased (p < 0.005, 0.01, 0.05) respectively, T.GSH level was significantly increased (p < 0.005) and serum ALT and AST activities were significantly decreased (p < 0.01, 0.05), respectively, when compared with CCl₄ group. These results show that Vit C has a highly protective effect on hepatotoxicity and oxidative stress caused by CCl₄. Copyright © 2009 John Wiley & Sons, Ltd.     

Trace elements and antioxidant enzymes in extremely low birthweight infants

Oxygen radicals are believed to contribute to typical diseases of prematurity, such as bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP) and necrotising enterocolitis (NEC). Our aim was to investigate whether these disorders are associated with disturbances in antioxidant enzyme activities and with low trace elements, which are co-factors of antioxidant enzymes. 209 infants with birthweight less than 1000 g were enrolled into a European multicentre randomised erythropoietin (rhEPO) trial; 155 developed one or more of the above mentioned diseases. We analysed Zn, Cu, Fe, Se in plasma and red blood cells (RBCs), superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in RBCs on the 3rd and 68th day of life. Zn, Fe, Se in plasma, and Se in RBCs decreased (p<0.01), and Zn in RBC (p<0.001), CuZn-SOD (p<0.01) and CAT increased (p<0.05), whereas GSH-Px remained unchanged. No differences were observed between the rhEPO and control groups. Antioxidant enzyme activities did not correlate with gestational age. In infants with BPD, IVH, ROP, or NEC, CuZn-SOD and CAT (p<0.05) were higher at day 68 than in infants without these diseases. CuZn-SOD and GSH-Px at 3 days and CuZn-SOD at 68 days correlated positively (p<0.05) with the duration of oxygen treatment. In conclusion, in ELBW infants, trace element concentrations decreased over the first 10 weeks of life. Lower trace element concentrations, did not affect the activities of CuZn-SOD, GSH-Px, and CAT. Typical diseases of prematurity were not associated with decreased antioxidant enzyme activities.     

The susceptibility to autoxidation of erythrocytes in diabetic mice: Effects of melatonin and pentoxifylline

Oxidative stress had a great importance in development of complications in diabetes. We investigated effects of melatonin and pentoxifylline in diabetic mice. Swiss albino mice (n = 40) were divided into four groups: alloxan‐induced diabetes mellitus (DM), alloxan‐induced diabetes with melatonin supplementation (DM + MLT), alloxan‐induced diabetes with pentoxifylline supplementation (DM + PTX), and control. Glutathione‐peroxidase (GSH‐Px) activity, malondialdehyde (MDA) and reduced glutathione (GSH) levels, and susceptibility to oxidation of erythrocytes were measured. MDA levels were higher than control in the DM and DM + MLT. The DM had more MDA level than the DM + MLT and DM + PTX (P < 0.001). After in vitro oxidation, MDA levels of all groups were found higher than the control. However, they were significantly lower than the DM in DM + PTX and DM + MLT (P < 0.001). Although GSH levels of the DM and DM + PTX were less than the control, GSH‐Px activity of the DM was lower than the control and DM + PTX (P < 0.05). We suggest that there is increased oxidative stress and compromised antioxidant status of erythrocytes in diabetes; however, it can be effectively prevented by melatonin or pentoxifylline supplementation.     

Antioxidant status and lipid peroxidation in hemodialysis patients undergoing erythropoietin and erythropoietin-vitamin E combined therapy

In this study, plasma and red blood cell (RBC) antioxidant status and plasma lipid peroxidation were investigated in 46 hemodialysis patients. In addition, the effect of erythropoietin (EPO) and EPO-vitamin E combination therapy on plasma and RBC antioxidant status, and plasma lipid peroxidation were examined.

There were 10 healthy subjects in the control group and 10 hemodialysis patients in the untreated group. The third group included 36 hemodialysis patients that were given EPO (100 U/kg) for 3 months, 3 times per week. The fourth group included 36 hemodialysis-patients from the EPO group that were given EPO at a 50% decreased dose + vitamin E (300 mg/day) for 3 months.

MDA levels in the untreated group, the EPO group and the EPO + vitamin E groups were found to be higher than the control group (p<0.001, in both). Furthermore, MDA levels in both of the treatment groups were lower when compared to the untreated group (p<0.001, in both). Plasma vitamin E levels in the untreated, the EPO group and EPO + vitamin E groups were lower than the control group (p<0.001). In contrast, plasma vitamin E levels in the treatment groups were higher in comparison with the control group (p<0.05). SOD activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p<0.001). SOD activities in the treatment groups were higher than the control group (p<0.001). The SOD activities in the EPO + vitamin E group increased when compared to the EPO group (p<0.001). CAT activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p<0.001 in untreated and EPO groups, p<0.01 in EPO + vitamin E group). CAT activities in EPO and EPO + vitamin E groups were increased when compared to the untreated group (p<0.01).

In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in hemodialysis patients. EPO has an antioxidant effect on the RBC and plasma antioxidant status, and plasma lipid peroxidation. These effects were moderately increased by the combination of vitamin E and EPO.     

Effects of Nigella sativa L. and Urtica dioica L. on selected mineral status and hematological values in CCl4-treated rats

This study was designed to investigate the effects of Nigella sativa L. (NS), known as black seed, or/and Urtica dioica L. (UD), known as stinging nettle root, treatments on serum Na, K, Cl, and Ca levels and some hematological values of CCl₄-treated rats. Sixty healthy male Sprague-Dawley rats, weighing 250–300 g, were randomly allotted into 1 of 4 experimental groups: A (CCl₄-only treated), B (CCl₄+UD treated), C (CCl₄+NS treated), and D (CCl₄+UD+NS treated), each containing 15 animals. All groups received CCl₄ (0.8 mL/kg of body weight, subcutaneously, twice a week for 90 d starting d 1). In addition, B, C, and D groups also received the daily ip injection of 0.2 mL/kg NS and/or 2 mL/kg UD oils for 45 d starting d 46. Group A, on the other hand, received only 2 mL/kg normal saline solution for 45 d starting d 46. Blood samples for the biochemical analysis were taken by cardiac puncture from five randomly chosen rats in each treatment group at the beginning, d 45, and d 90 of the experiment. The CCl₄ treatment for 45 d significantly (p<0.05) increased the serum K and Ca and decreased (p<0.05) the red blood cell count (RBC), white blood cell count (WBC), packed cell volume (PCV), and Hb levels without changing (p>0.05) the serum Na and Cl levels. NS or UD treatments (alone or combination) for 45 d starting d 46 significantly (p<0.05) decreased the elevated serum K and Ca levels and also increased (p<0.05) the reduced RBC, WBC, PCV, and Hb levels. It is concluded that NS and/or UD treatments might ameliorate the CCl₄-induced disturbances of anemia, some minerals, and body’s defense mechanism in CCl₄-treated rats.     

Effects of taurine on oxidative stress parameters and chromium levels altered by acute hexavalent chromium exposure in Mice Kidney tissue

The kidney has been regarded as a critical organ of toxicity induced by acute exposure to hexavalent chromium [Cr(VI)] compounds. Reactive intermediates and free radicals generated during reduction process might be responsible for Cr(VI) toxicity. In this study, the effects of pretreatment or posttreatment of taurine on Cr(VI)-induced oxidative stress and chromium accumulation in kidney tissue of Swiss albino mice were investigated. Single intraperitoneal (ip) potassium dichromate treatment (20 mgCr/kg), as Cr(VI) compound, significantly elevated the level of lipid peroxidation as compared with the control group (p<0.05). This was accompanied by significant decreases in nonprotein sulfhydryls (NPSH) level, superoxide dismutase (SOD), and catalase (CAT) enzyme activities as well as a significant chromium accumulation (p<0.05). Taurine administration (1 g/kg, ip) before or after Cr(VI) exposure resulted in reduction of lipid peroxidation levels and improvement in SOD enzyme activity (p<0.05). On the other hand, administration of the antioxidant before Cr(VI) exposure restored the NPSH level and CAT enzyme activity and also reduced tissue chromium levels (p<0.05), whereas postreatment had only slight effects on these parameters. In view of the results, taurine seems to exert some beneficial effects against Cr(VI)-induced oxidative stress and chromium accumulation in mice kidney tissue.     

Protective role of intraperitoneally administered vitamins C and E and selenium on the levels of lipid peroxidation in the lens of rats made diabetic with streptozotocin

The aim of this work was to determine the protective effects of intraperitoneally administered vitamins C and E and selenium on the lipid peroxidation (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (rGSH) activities in the lens of rats induced diabetic with streptozotocin (STZ). Lenses in the diabetic control group had a slightly higher mean level of MDA compared with lenses of the vitamin E and selenium groups, although the mean levels of MDA were significantly lower in control, combination, and vitamin C groups than in the diabetic control group (p < 0.05 andp < 0.01). However, MDA levels were significantly lower in vitamin C, vitamin E, and combination groups than in controls (p < 0.01). The GSH-Px activities of lenses were significantly higher in vitamin C-, vitamin E- and selenium-injected groups than that in the diabetic control group (p < 0.01), whereas, the activity of GSH-Px was significantly lower in the diabetic control group than in the control group. In addition, the rGSH content was seen to decrease only in the vitamin C group compared to both control and diabetic control groups (p < 0.05). In conclusion, the results from these experiments indicate that vitamins C and E and selenium can protect the lens against oxidative damage, but the effect of vitamin C appears to be much greater than that of vitamin E and selenium.     

The protective effect of curcumin on cardiac markers and fibrosis in abemaciclib-induced cardiac damage in rats

Abemaciclib (ABE) is a cyclin-dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 µL), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin-I, total cholesterol, and creatine kinase myocardial band (CK-MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK-MB, troponin-I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage.     

Effect of black cumin (Nigella sativa) on cadmium-induced oxidative stress in the blood of rats

The protective effect of black cumin (Nigella sativa=NS) on cadmium-induced oxidative stress was studied in rats. The rats were randomly divided into three experimental groups: A (conrol), B (Cd treated), and C (Cd+NS treated), each containing 10 animals. The Cd-treated and Cd+NS-treated groups were injected subcutaneously daily with CdCl₂ dissolved in isotonic NaCl in the amount of 2 mL/kg for 30 d, resulting in a dosage of 0.49 mg Cd/kg/d. The control group was injected with only isotonic NaCl (2 mL/kg/d) throughout the experiment (for 30 d). Three days prior to induction of CdCl₂, the Cd+NS-treated group received a daily intraperitoneal injection of 0.2 mL/kg NS until the end of the study. Cd treatment increased significantly the malondialdehyde levels in plasma and erythrocyte (p<0.01 and p<0.05, respectively) and also increased significantly the antioxidant levels (superoxide dismutase, glutathione peroxidase, and catalase) (p<0.05) compared to the control group. Cd+NS treatment decreased significantly the elevated malondialdehyde levels in plasma and erythrocyte (p<0.01 and p<0.05, respectively) and also reduced significantly the enhanced antioxidant levels (p<0.05). Cd treatment increased significantly the activity of iron levels (p<0.05) in the plasma compared to the control group. Cd+NS treatment decreased the activity of iron levels (p<0.05) in the plasma compared to the Cd-treated group. In the control group with no treatment, histology of erythrocytes was normal. In the Cd-treated group, there were remarkable membrane destruction and hemolytic changes in erythrocytes. In the Cd+NS treated group, these changes were less than in the Cd-treated group. Our results show that N. sativa exerts a protective effect against cadmium toxicity.     

Protective role of intraperitoneally administered vitamin E and selenium on the antioxidative defense mechanisms in rats with diabetes induced by streptozotocin

The aim of this work was to determine the protective effects of intraperitoneally administered vitamin E and selenium (as Na₂SeO₃, Se) on the lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and vitamin E levels, glutathione peroxidase (GSH-Px), reduced glutathione (GSH) activities in the plasma, red blood cell (RBC), liver, and muscle of rats with streptozotocin-induced diabetes. Fifty adult male Wistar rats were used and all rats were randomly divided into five groups. The first group was used as a control and the second group as a diabetic control. A placebo was given to first and second groups by injection. The third group was intraperitoneally administered with vitamin E (20 mg over 24 h), the fourth group with Se (0.3 mg over 24 h), and the fifth group with vitamin E and Se combination (COM) (20 mg vitamin E + 0.3 mg Se over 24 h). This administration was done for 25 days and the TBARS, vitamin E, GSH-Px, GSH levels in the plasma, RBC, liver, and muscle samples were determined. The vitamin E level in the plasma and liver was significantly (p < 0.05) higher in the control than in the diabetic control group. Also, the TBARS levels in the RBC, liver, and muscle were significantly (p < 0.05) lower in the control than in the diabetic control group. However, GSH-Px and GSH activities in RBC, liver, and muscle were not statistically different between the control and the diabetic control groups. The vitamin E levels in plasma and liver (p < 0.01 and p < 0.001) and GSH-Px activities (p < 0.01, p < 0.001) in RBC were significantly higher in vitamin E, Se, and COM groups than in both control and diabetic control groups. However, the TBARS levels of RBC, muscle, and liver in vitamin E and Se administered groups were significantly (p < 0.05-p < 0.001, respectively) decreased. These results indicate that intraperitoneally administered vitamin E and Se have significant protective effects on the blood, liver, and muscle against oxidative damage of diabetes. The abstract of this study was presented in Physiological Research 48(Suppl. 1), S99 (1999).     

Neuroprotective effect of melatonin on radiation-induced oxidative stress and apoptosis in the brainstem of rats

This study aimed to determine the effects of melatonin on irradiation-induced apoptosis and oxidative stress in the brainstem region of Wistar rats. Therefore, the animals underwent whole-brain X-radiation with a single dose of 25 Gy in the presence or absence of melatonin pretreatment at a concentration of 100 mg/kg BW. The rats were allocated into four groups (10 rats in each group): namely, vehicle control (VC), 100 mg/kg of melatonin alone (MLT), irradiation-only (RAD), and irradiation plus 100 mg/kg of melatonin (RAM). An hour before irradiation, the animals received intraperitoneal (IP) melatonin and then were killed after 6 hr, followed by measurement of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total antioxidant capacity (TAC) in the brainstem region. Furthermore, the western blot analysis technique was performed to assess the caspase-3 expression level. Results showed significantly higher MDA and NO levels in the brainstem tissues for the RAD group when compared with the VC group (p < .001). Moreover, the irradiated rats exhibited a significant decrease in the levels of CAT, SOD, GPx, and TAC (p < .01, p < .001, p < .001, and p < .001, respectively) in comparison to the VC group. The results of apoptosis assessment revealed that the expression level of caspase-3 significantly rose in the RAD group in comparison with the VC group (p < .001). Pretreatment with melatonin ameliorated the radiation-induced adverse effects by decreasing the MDA and NO levels (p < .001) and increasing the antioxidant enzyme activities (p < .001). Consequently, the caspase-3 protein expression level in the RAM group showed a significant reduction in comparison with the RAD group (p < .001). In conclusion, melatonin approximately showed a capacity for neuroprotective activity in managing irradiation-induced oxidative stress and apoptosis in the brainstem of rats; however, the use of melatonin as a neuroprotective agent in humans requires further study, particularly clinical trials.     

Trace element concentrations and superoxide dismutase and catalase activities in benign and malignant larynx tumors

The plasma and erythrocyte levels of zinc, copper, and magnesium and the activities of red-cell copper-zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) were determined in patients with benign and malignant tumors of the larynx. Blood samples from patients and healthy controls were drawn using heparinized tubes. The erythrocyte Cu/Zn-SOD and CAT activities were determined spectrophotometrically and the zinc, copper, and magnesium concentrations were determined in erythrocyte and plasma by atomic absorption spectrometry. Variance analysis was employed in the statistical evaluation of the findings. There was a significant increase in red-cell Cu/Zn-SOD activity in the subjects with malignant and benign tumors compared to controls (p<0.001). The CAT activity increased only in the benign tumor group (p<0.01). The plasma zinc concentrations were significantly lower in the malignant tumor group (p<0.05) and significantly higher in the benign tumor group (p<0.01). The erythrocyte copper concentrations were significantly lower in both benign and malignant tumor groups (p<0.001). The plasma copper and magnesium and the erythrocyte magnesium concentrations did not show significant differences relative to controls (p>0.05). The increases in the activities of SOD and CAT activities and the changes in trace elements concentrations can indicate the presence of increased reactive oxygen species that might play a part in the pathogenesis larynx tumors. Presented at the IX Asian-Pacific Congress of Clinical Biochemistry, March 9–14, 2002, New Delhi, India.     

Synergistic hepatoprotective effect of Schisandrae lignans with Astragalus polysaccharides on chronic liver injury in rats

The aim of this study was to investigate the synergistic hepatoprotective effect of lignans from Fructus Schisandrae chinensis (LFS) with Astragalus polysaccharides (APS) on chronic liver injury in male Sprague-Dawley rats. Subcutaneous injection of 10% CCl₄ twice a week for 3 months resulted in significantly (p<0.001) elevated serum alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP) activities compared to controls. In the liver, significantly elevated levels (p<0.001) of malondialdehyde (MDA), lowered levels of reduced glutathione (GSH) (p<0.05) and catalase (CAT) (p<0.001), superoxide dismutase (SOD) (p<0.01)were observed following CCl₄ administration. ‘LFS+ASP’ treatment of rats at doses of ‘LFS (45 mg/kg)+APS (150 mg/kg)’ and ‘LFS (135 mg/kg)+APS (450 mg/kg)’ displayed hepatoprotective and antioxidative effects than the administration of either LFS or APS, as evident by lower (p<0.005 or 0.001) levels of serum ALT, AST, ALP and hepatic MDA (p<0.001) concentration, as well as higher SOD (p<0.05 or 0.005), CAT activities(p<0.01 or 0.005), GSH concentration (p<0.05 or 0.005) compared to the toxin treated group. Histopathological examinations revealed severe fatty degeneration in the toxin group, and mild damage in groups treated with ‘LFS+APS’ were observed. The coefficients drug interaction (CDI) between each individual drug and their combination (at the same dose of their single treatment) of these foregoing parameters were all less than 1, indicating that LFS and APS display hepatoprotective and antioxidant properties and act in a synergistic manner in CCl₄ induced liver injury in rats.     

The Protective and Antidotal Effects of Taurine on Hexavalent Chromium-Induced Oxidative Stress in Mice Liver Tissue

Acute exposure to hexavalent chromium [Cr(VI)] compounds can cause hepatotoxicity. Reactive intermediates and free radicals generated during reduction process may be responsible for Cr(VI) toxicity. In this study, the effects of pretreatment or posttreatment of taurine on Cr(VI)-induced oxidative stress and chromium accumulation in liver tissue of Swiss Albino mice were investigated. Single intraperitoneal (ip) potassium dichromate treatment (20 mgCr/kg), as Cr(VI) compound, significantly elevated the level of lipid peroxidation as compared with control group (p < 0.05). This was accompanied by significant decreases in nonprotein sulfhydryls (NPSHs) level, superoxide dismutase (SOD), and catalase (CAT) enzyme activities as well as a significant chromium accumulation in the tissue (p < 0.05). Taurine administration (1 g/kg, ip) before or after Cr(VI) exposure resulted in reduction of lipid peroxidation (p < 0.05) showed rebalancing effect on tissue NPSH levels either in pretreatment or in posttreatment (p < 0.05). Enzyme activities of SOD and CAT were restored by taurine pretreatment (p < 0.05), whereas posttreatment had less pronounced effects on these parameters. On the other hand, taurine treatment, before or after exposure, could exert only slight decreases in tissue Cr levels (p > 0.05). In view of the results, taurine seems to exert some beneficial effects against Cr(VI)-induced oxidative stress in liver tissue.     

Investigation of the protective effect of ellagic acid for preventing kidney injury in rats exposed to nicotine during the fetal period

We investigated the possible protective effects of ellagic acid on rat kidneys exposed to nicotine during the fetal period. Twenty pregnant female rats were divided randomly into four groups: control (C), nicotine (N), ellagic acid (EA) and nicotine + ellagic acid (N + EA). Nicotine and ellagic acid treatments were continued throughout the pregnancies and for 15 days after delivery. On day 15, all neonatal pups were sacrificed and their kidneys were removed for biochemical and histopathological examination. The nicotine treatment significantly decreased body weight, total glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and increased malondialdehyde (MDA) and nitric oxide (NO) levels in the N group compared to controls. EA treatment ameliorated decreased body weight, GSH, GSH-Px and SOD activities, and increased MDA and NO levels in group N + EA compared to group N (p < 0.05). Nicotine caused kidney damage as shown by incomplete development of glomeruli and Bowman's capsules. Nicotine also caused greater apoptosis in group N compared to group C. Ellagic acid treatment produced histological kidney structure that was closer to normal and it exerted an anti-apoptotic effect in the N + EA group compared to the N group. EA played a protective role against nicotine-induced nephrotoxicity and oxidative stress in rats owing to its antioxidant, radical scavenging and anti-apoptotic effects.