IRFI 042 reduces oxidative stress against kainic acid toxicity in the rat brain

We investigated if IRFI 042, an analog of vitamin E, protects the brain against oxidative stress induced by intraperitoneal administration of Kainic acid (KA) (10 mg/kg); sham brain injury rats were used as controls. Animals received either IRFI 042 (20 mg/kg) or its vehicle 30 min before KA injection and after 6 h were sacrificed to measure malonildyaldheide (MDA) and glutathione levels (GSH) in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of IRFI decreased MDA (micromol/g wet tissue: KA + vehicle = 22.5 ± 4.2; KA + IRFI = 17.1 ± 1; P < 0.005) and prevented GSH loss (nmol/g wet tissue: KA + vehicle = 0.41 ± 0.1; KA + IRFI = 1.86 ± 0.2; P < 0.005) in the diencephalon. The latency of occurrence of behavioral signs increased from 39 ± 1 to 62 ± 6 min in IRFI 042 group. The data suggest that IRFI 042 might protect against KA‐induced oxidative stress.     

Levetiracetam protects against kainic acid-induced toxicity

We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1beta (IL-1beta) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 +/- 0.03 nmol/mg protein; KA + LVT = 0.13 +/- 0.01 nmol/mg protein; P < 0.005), and in the diencephalons (KA + vehicle = 1,01 +/- 0.2 nmol/mg protein; KA + LVT = 0,33 +/- 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 +/- 1 micromol/g protein; KA + LVT = 15 +/- 2 micromol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 +/- 0.8 micromol/g protein; KA + LVT = 13 +/- 0.3 micromol/g protein; P < 0.05), reduced brain IL-1beta mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuro-protective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation.     

The effect of melatonin on lipid peroxidation and nitrite/nitrate levels, and on superoxide dismutase and catalase activities in kainic acid-induced injury

Kainic acid (KA) initiates neuronal injury and death by inducing oxidative stress and nitric oxide release from various regions of the brain. It was recently shown that melatonin has free radical-scavenging action and may protect against kainate-induced toxicity. In order to assess the possible supportive effect of melatonin treatment in KA-induced injury in the rat brain cortex, we determined malondialdehyde (MDA) levels as an index of lipid peroxidation, and assessed the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of nitrite/nitrate 35 male rats were divided into five groups, each receiving a different intraperitoneal treatment: saline solution (0.2 ml), kainic acid (15 mg/kg), melatonin (20 mg/kg), KA then melatonin (each as above, 15 min apart), or melatonin then KA (each as above, 30 min apart). Administration of KA caused an about five-fold increase in the catalase activity and an increase in the SOD activity in the cortex relative to the activities for the controls. Treatment with melatonin 15 min after KA injection kept malondialdehyde levels and catalase and superoxide dismutase activities at the normal levels, and led to an increase in the levels of nitrite/nitrate. Our data suggests that melatonin treatment following KA administration has a protective effect on antioxidant enzyme activities and thus supports the role of melatonin and oxidative stress in the regulation of antioxidative enzyme activity.     

Fluoride-Induced Oxidative Stress in Rat’s Brain and Its Amelioration by Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Pineal Proteins and Melatonin

Fluoride (F) becomes toxic at higher doses and induces some adverse effects on various organs, including brain. The mechanisms underlying the neurotoxicity caused by excess fluoride still remain unknown. The aims of this study were to examine F-induced oxidative stress (OS) and role of melatonin (MEL) and buffalo pineal proteins (PP) against possible F-induced OS in brain of rats. The 24 rats were taken in present study and were divided into four groups: control, F, F + PP, and F + MEL. The F group was given 150 mg/L orally for 28 days. Combined 150 ppm F and 100 μg/kg BW (i.p.) PP and F (150 ppm) + MEL (10 mg/kg BW, i.p.) were also administered. The activities of enzymatic, viz., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), and non-enzymatic, viz., reduced glutathione (GSH) concentration, and the levels of malondialdehyde (MDA) in the brain tissue were measured to assess the OS. Fluoride administration significantly increased brain MDA compared with control group, while GSH levels were decreased in fluoride-treated groups, accompanied by the markedly reduced SOD, GPx, GR, and SOD activity. Buffalo PP and MEL administration caused brain MDA to decrease but caused SOD, GPx, GR, GSH, and CAT activities to increase to significant levels in F-treated animals. Together, our data provide direct evidence that buffalo PP and MEL may protect fluoride-induced OS in brain of rats through mechanisms involving enhancement of enzymatic and non-enzymatic antioxidant defense system. Therefore, this study suggested that PP and MEL can be useful in control of neurotoxicity induced by fluoride.     

Protective effect of silymarin on oxidative stress in rat brain

Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.     

Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.     

Ganoderma atrum polysaccharide attenuates oxidative stress induced by d-galactose in mouse brain

AimsGanoderma atrum polysaccharide (PSG-1), the main constituent of G. atrum, has been reported to attenuate oxidative stress in vitro. The aim of this study was to investigate whether PSG-1 has a protective effect on the brain against oxidative stress induced by d-galactose (D-gal) in vivo.Main methodsMice were intraperitoneally (i.p.) injected with D-gal (100 mg/kg body weight) once daily for 10 weeks. From the seventh week, D-gal-treated mice received PSG-1 (50, 100, or 150 mg/kg body weight) once daily for the last 4 weeks. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GSH-Rd), and the contents of glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) in the brain were measured using different biochemical methods to evaluate the changes of the antioxidant ability in the PSG-1 treated mice. Apoptosis, reactive oxygen species (ROS) and calcium levels were determined by flow cytometry.Key findingsAdministration of PSG-1 significantly reduced apoptosis in the mouse brain in a dose-dependent manner. PSG-1-evoked reduction of apoptosis was associated with the decrease of MDA and GSSG contents, and the increase of SOD, CAT, GPx and GSH-Rd activities, and GSH contents. PSG-1 treatment was also found to attenuate ROS production and calcium accumulation.SignificancePSG-1 has a potential to be used as a novel therapeutic agent for the protection of aging brain tissue against oxidative damage by modifying the redox system and maintaining calcium homeostasis.     

Role of soy isoflavone in preventing aging changes in rat testis: Biochemical and histological studies

Testicular function and structure harmed by ageing. Goal of this research was to assess preventive actions of soy isoflavone oral administration for 8 weeks on testes of old male albino rats, and potential mechanisms of action. Adult control (N = 10) and elderly control (N = 10) rats were fed usual diet, while aged treatment group (N = 10) gave oral 100 mg/kg soy isoflavone daily for 8 weeks. ELISA kits were used to measure testosterone levels and oxidative stress indicators [malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD)] in serum. Aging produced functional and structural testicular changes and decreased ki67 proliferative marker immunoexpression versus adult control rats due to enhancement of oxidative stress. Soy isoflavone exerted protective effect on testicular function and structure as assessed by increase serum levels of testosterone and preserved histological structure and immune-expression features. These protected effects due to isoflavone antioxidant properties proved by decrease in serum values of MDA, while GSH and SOD were elevated after treatment. These data demonstrated protective effects of isoflavone against age changes in rat testes, by reducing oxidative stress and increasing antioxidants and testicular ki67 proliferative marker immunoexpression.     

Response of lead-induced oxidative stress and alterations in biogenic amines in different rat brain regions to combined administration of DMSA and MiADMSA

The present study was planned to investigate if combined administration of meso-2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) could achieve better recovery in the altered biochemical parameters suggestive of brain oxidative stress and depletion of lead from blood and brain following acute lead exposure. Male Wistar rats were exposed to lead nitrate (50 mg/kg, i.p., once daily for 5 days) followed by treatment with the above chelating agents using two different doses of 25 or 50 mg/kg (orally) either alone and in combination once daily for five consecutive days. Lead exposure resulted in the significant inhibition of δ-aminolevulinic acid dehydratase activity and depletion of glutathione (GSH) in blood. These changes were accompanied by significant reduction in blood hemoglobin, RBC levels and superoxide dismutase and catalase activities. Significant increase in blood reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels were noted. We observed marked increase in brain ROS level while GSH/oxidized glutathione ratio showed significant decrease accompanied by a significant increase in blood and brain lead concentration. The levels of norepinephrine, dopamine and serotonin in different brain regions were also altered on lead exposure. Co-administration of DMSA and MiADMSA particularly at the lower dose was most effective in the recovery of lead-induced changes in the hematological variables and oxidative stress and resulted in more pronounced depletion of lead from blood and brain compared to monotherapy with these chelators. On the other hand, combined administration of MiADMSA (50 mg/kg) in combination with DMSA (25 mg/kg each) had additional beneficial effect over the individual effect of chelating agent in the recovery of altered levels of brain biogenic amines. The study suggests that administration of MiADMSA is generally a better lead chelator than DMSA while combined administration of DMSA and MiADMSA might be a better treatment option compared to monotherapy at least in the removal of lead from the target tissues.     

Severe total hepatic ischemia and reperfusion: relationship between very high alpha-tocopherol uptake and lipid peroxidation.

Reperfusion injury of the liver occurs in liver transplantation and in major hepatectomies. It triggers a severe oxidative stress that leads to increased lipid peroxidation. In our study we examined the effect of parenteral supranutritional administration of alpha-tocopherol, a vitamin that plays a key role in the endogenous antioxidant system, to rats subjected to severe ischemia/reperfusion (I/R) injury of the liver. alpha-Tocopherol was administered to the animals at doses of 30 and 300 mg/kg bw, whereas total hepatic ischemia was induced for 60 min followed by 120 min reperfusion. Tissue and blood samples were collected for malonyldialdehyde (MDA) and serum alpha-tocopherol assay, respectively. In the sham operation group, mean MDA level in liver was 1.14 nmole/g wet tissue in the control subgroup, and 1.01 or 0.74 nmole/g wet tissue in the subgroups given 30 or 300 mg/kg alpha-tocopherol. In the I/R group, mean MDA level was 1.57 nmole/g wet tissue in the control subgroup, and 0.97 and 0.77 nmole/g wet tissue in the subgroups given 30 or 300 mg/kg alpha-tocopherol. Mean levels of alpha-tocopherol in serum (mumole/l) were 10.20 and 1.80 in the control subgroups, 25.28 and 11.25 in the subgroups treated with 30 and 300 mg/kg bw of alpha-tocopherol, and 31.00 and 13.02 in the subgroups treated with 30 and 300 mg/kg bw of alpha-tocopherol, within the sham-operation and I/R groups, respectively. A significant decrease of MDA accompanied by a significant increase of serum alpha-tocopherol was documented in the alpha-tocopherol-treated rats within both groups. Ischemia/reperfusion triggered a significant increase of the MDA level in the liver of the rats not treated with alpha-tocopherol as compares with the treated animals.     

The effects of desferrioxamine and quercetin on hepatic ischemia-reperfusion induced renal disturbance

BACKGROUND: The aim of this study was to analyze the effects of 45min of hepatic ischemia and 1h of reperfusion on renal oxidative stress parameters, on renal tissue damage, and the role of Desferrioxamin (Dfx) and Q on these parameters. METHODS: Thirty Wistar albino rats were randomized to five groups. Group I was the control group. Group II received no treatment. Groups III and IV received intramuscular injections of desferrioxamine (100mg/kg) and quercetin (50mg/kg), respectively. Group V was administered Dfx and quercetin in combination. After treatment for 3 days, groups II, III, IV, and V were exposed to total hepatic ischemia for 45min. Plasma alanine aminotransferase levels, renal malondialdehyde and reduced glutathione (GSH) activities were measured after reperfusion for 1h. Histopathological and ultrastructural analysis of renal tissues was carried out. RESULTS: Plasma creatinine and BUN levels were markedly increased in the IR group and pretreated groups. Kidney MDA increased in the IR group, Q and Dfx+Q significantly decreased kidney MDA Kidney GSH levels markedly decreased in the IR group, Dfx significantly increased kidney GSH. No evidence of overt injury was observed in any renal tissue under light and electron microscopy. CONCLUSIONS: Our data demonstrated that 45min of hepatic ischemia and 1h of reperfusion may alter renal functions and may cause oxidative stress on renal tissue. Q and Dfx seem to have a beneficial effect via the GSH system and modulation of MDA levels.     

Neuroprotective Effect of Etomidate in the Central Nervous System of Streptozotocin-Induced Diabetic Rats

It is well known that hyperglycaemia due to diabetes mellitus leads to oxidative stress in the central nervous system. Oxidative stress plays important role in the pathogenesis of neurodegenerative changes. In the present study we investigated the possible neuroprotective effect of etomidate against streptozotocin-induced (STZ-induced) hyperglycaemia in the rat brain and spinal cord. A total of 40 rats were used in this study. Rats were divided into four groups: sham-control, diabetic, diabetic-etomidate treated and vehicle for etomidate treatment group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Three days after streptoztocin injection, etomidate (2 mg/kg) was injected intraperitoneally for etomidate group and lipid emulsion (10%) for vehicle group was injected with corresponding amount intraperitoneally every day for 6 weeks. Six weeks after streptozotocin injection, seven rats from each group were killed and brain, brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for the biochemical analysis (the level of malondialdehyde [MDA], total nitrite, reduced glutathione [GSH], and xanthine oxidase [XO] activity). STZ-induced diabetes resulted in significantly elevation of MDA, XO and nitrite levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the rats (P < 0.05) while etomidate treatment provided significantly lower values (P < 0.05). This study demonstrated that etomidate have neuroprotective effect on the neuronal tissue against the diabetic oxidative damage.     

Protective action of honokiol, administered orally, against oxidative stress in brain of mice challenged with NMDA

Neuroprotective effect of honokiol (HK), orally administered, on oxidative damage in the brain of mice challenged with N-methyl-d-aspartic acid (NMDA) was examined. HK (1-100 mg/kg) was administered to Institute of Cancer Research (ICR) male mice through a gavage for 3 days consecutively, and on the third day, NMDA (150 mg/kg) was intraperitoneally (i.p.) administered. Administration of NMDA, causing a lethality of approximately 60%, resulted in a significant decrease of total glutathione (GSH) level and increase of thiobarbituric acid-reactive substances (TBARS) value in brain tissue. Meanwhile, oral administration of HK (> or = 3 mg/kg) for 3 days reduced the lethality (60%) in NMDA-treated group to 10% level, and alleviated the behavioral signs of NMDA neurotoxicity. Moreover, HK pretreatment restored the levels of total GSH and TBARS in the brain tissue to control levels (p<0.01). Additionally, GSH peroxidase activity in cytosolic portion of brain homogenate was also restored significantly (p<0.01), whereas GSH reductase activity was not. Separately, compared to vehicle-treated control, no significant changes in body and brain weight were observed in mice administered with HK. Based on these results, oral intake of HK is suggested to prevent oxidative stress in the brain of mice.     

The protective effect of L-carnitine against hippocampal damage due to experimental formaldehyde intoxication in rats

We investigated the protective effects of L-carnitine on hippocampus tissue damage in rats during experimental formaldehyde (FA) intoxication. Male Wistar albino rats were assigned into four groups: (1) control (C), (??2) formaldehyde (FA), (3) formaldehyde + 0.5 g/kg of L-carnitine (FA + 0.5 LC) (4) formaldehyde + 1 g/kg L-carnitine (FA + 1 LC). At the end of the 14 day trial period, animals were sacrificed by decapitation under anesthesia. The hippocampus tissue samples were extracted to measure MDA, GSH and SOD activity. Neuronal degeneration was assessed based on histopathological (hematoxylin and eosin) and immunohistochemical (anti-ubiquitin) examination. To detect oxidative stress, specimens were reacted with anti-Cu/Zn-SOD antibody. After administering L-carnitine with FA to the animals, the activities of SOD and GSH increased, but the levels of MDA decreased in hippocampus tissue. Neuronal degeneration was observed in the FA group. L-carnitine administration reduced neuronal degeneration and histological structure was similar to controls. After FA application, degenerated hippocampus neurons were stained with anti-ubiquitin and Cu/Zn-SOD antibodies; weakly positive staining was observed in L- carnitine-treated groups. L-carnitine may be useful for preventing oxidative damage in the hippocampus tissue due to formaldehyde intoxication.     

Protective effects of melatonin on myocardial ischemia/reperfusion induced infarct size and oxidative changes

Free radicals, calcium overloading and loss of membrane phospholipids play an important role in the development of ischemia/reperfusion (I/R) injury. Melatonin is a well-known antioxidant and free radical scavenger. Melatonin may also reduce the intracellular calcium overloading and inhibit lipid peroxidation. This study was designed to investigate the effects of melatonin on the I/R-induced cardiac infarct size in an in vivo rat model. We also investigated glutathione (GSH) levels, an antioxidant the levels of which are influenced by oxidative stress, and malondialdehyde (MDA) levels, which is an index of lipid peroxidation. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Melatonin (10 mg/kg) or vehicle was given 10 min before ischemia via the jugular vein. Infarct size, expressed as the percentage of the risk zone, was found significantly greater in I/R group than in the melatonin-treated I/R group. MDA levels were significantly higher, but GSH levels were lower in the I/R group than in the control group. Melatonin significantly reduced the MDA values and increased the GSH levels. These results suggest that oxidative stress contributes to myocardial I/R injury and melatonin administration exerts a mitigating effect on infarct size. Furthermore, the results indicated that melatonin improves the antioxidant capacity of the heart and attenuates the degree of lipid peroxidation after I/R.     

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion–Detorsion Model

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion–detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia–reperfusion; 4. Zinc + ischemia–reperfusion; 5. Melatonin + ischemia–reperfusion; 6. Zinc + melatonin + ischemia–reperfusion. Zinc and melatonin were administered before ischemia–reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion–detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p < 0.001). Torsion–detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p < 0.001). Serum inhibin-B and spermatogenic activity levels in the torsion–detorsion group were also significantly lower than those in the other groups (p < 0.001). However, zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p < 0.001). The results of the study show that zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia–reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.     

Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats

Acrylamide (ACR), used in many fields from industrial manufacturing to laboratory personnel work is also formed during the heating process through interactions of amino acids. Therefore ACR poses a significant risk to human health. This study aimed to elucidate whether resveratrol (RVT) treatment could modulate ACR-induced oxidative DNA damage and oxidative changes in rat brain, lung, liver, kidney and testes tissues. Rats were divided into four groups as control (C); RVT (30 mg/kg i.p. dissolved in 0.9% NaCl), ACR (40 mg/kg i.p.) and RVT + ACR groups. After 10 days rats were decapitated and tissues were excised. 8-hydroxydeoxyguanosine (8-OHdG) is a biomarker of oxidative DNA damage. 8-OHdG content in the extracted DNA solution was determined by enzyme-linked immunosorbent assay method. Malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase activity (MPO) were determined in tissues, while oxidant-induced tissue fibrosis was determined by collagen contents. Serum enzyme activities, cytokine levels, leukocyte apoptosis were assayed in plasma. As an indicator of oxidative DNA damage, 8-OHdG levels significantly increased in ACR group and this was reversed significantly by RVT treatment. In ACR group, GSH levels decreased significantly while the MDA levels, MPO activity and collagen content increased in the tissues suggesting oxidative organ damage. In RVT-treated ACR group, oxidant responses reversed significantly. Serum enzyme activities, cytokine levels and leukocyte late apoptosis which increased following ACR administration, decreased with RVT treatment. Therefore supplementing with RVT can be useful in individuals at risk of ACR toxicity.     

The potential antioxidant effect of raloxifene treatment: a study on heart, liver and brain cortex of ovariectomized female rats

The antioxidant activity of some compounds buffer the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Recent studies documented that raloxifene has antioxidant properties in vitro. However, there are limited animal studies available to show raloxifene's antioxidant properties. We aimed to investigate the effects of raloxifene on antioxidant enzymes such as SOD, CAT and GPX, TrxR and the levels of GSH and MDA in heart, liver and brain cortex of ovariectomized female rats. Female Sprague Dawley rats weighing 300-350 g (n=24) were divided into three groups: (I) Eight non-ovariectomized rats were used as naive controls without any treatment (non-ovariectomized group, n=8). Five weeks after ovariectomy, (II) Ovariectomized placebo group (n=8) was given physiological saline, and (III) Raloxifene group (n=8) was given raloxifene 1 mg/kg sc. daily for 12 days. Ovariectomy induced significant increases on SOD, GPX, CAT activity and MDA levels in brain, heart and liver tissues compared to non-ovariectomized rats ( p<0.05). Raloxifene treatment led to decreased levels of SOD activity in heart, GPX activity in brain and CAT activity in liver tissue when compared to ovariectomized group ( p<0.05) but there was no change in activity of TrxR in all groups. The levels of MDA in brain, heart and liver tissues increased in ovariectomized group when compared to non-ovariectomized rats ( p<0.05). Raloxifene had a significant attenuating effect on the levels of MDA in brain and heart tissues. Our results also indicate that the levels of GSH in brain, heart and liver tissue decreased when compared to non-ovariectomized rats. Raloxifene treatment was observed to significantly increase the levels of GSH in brain and heart tissues ( p<0.05). However, there were insignificant differences for the GSH levels in liver tissues of ovariectomized placebo or raloxifene groups. In conclusion, our results demonstrate that raloxifene may be more effective against oxidative stress in heart and brain than in liver tissue.