Elevated Thiobarbituric Acid Reactive Substances Research Articles

Toxicity and biochemical responses induced by phosmet in rainbow trout (Oncorhynchus mykiss).

Phosmet is a non-systemic organophosphorus insecticide exerting its toxicity by inhibiting acetylcholinesterase upon entering the body via contact, ingestion and inhalation. Data regarding its sublethal effects on fish are limited, and therefore, with this study it was aimed to investigate the effects of phosmet on liver and brain tissues of juvenile Oncorhynchus mykiss following 24, 48, 72 and 96h of exposure to 5, 25 and 50μg/l concentrations. Pesticide treatment caused notable decrease in the levels of serum glucose, protein and cholesterol, whereas there was prominent elevation in the activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Anticholinesterase activity of phosmet was observed in brain tissue reaching maximum of 46%. In both tissues, increase in the activities of superoxide dismutase, catalase and glutathione peroxidase and level of glutathione was accompanied by elevated thiobarbituric acid reactive substances level. Our results clearly indicate the modulatory effect of phosmet on acetylcholinesterase activity and its potency to provoke oxidative stress condition. The determined alteration in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities indicates hepatotoxic potential of pesticide; meanwhile, obtained hypoglycaemia and hypoproteinaemia are evaluated as adaptive responses to handle the stress to survive.

Protective Effects of A. sativa against Oxidative Stress-Induced Liver Damage in Ovariectomized Mice

Postmenopausal women express great failure in their ovarian hormone production, especially estrogen. This deficiency may promote hypercholesterolemia and accelerate the redox imbalance. The present study was designed to evaluate the protective effect of Avena sativa against estrogen deficiency-induced liver and uterus oxidative injury in experimental ovariectomized mice. Female mice were randomly divided into five groups: group one (negative control) received normal diet and distilled water (C), group two (positive control) received daily enriched diet with oat grains and was kept on tap distilled water at a dose of 200 mg kg−1 d−1 (A), group three (ovariectomized mice) was nontreated fed with normal diet (O), group four includes ovariectomized mice treated daily with estradiol given by intraperitoneal injection at a dose of 100 μg kg−1 d−1 (OE), and the fifth group also includes ovariectomized mice which received enriched diet with oat grain parts with the same dose given to group two. The treatment period lasted two consecutive months. Both oat and hormonal treatments of ovariectomized groups resulted in a significant reduction in triglycerides and total cholesterol and increased high-density lipoprotein (HDL) levels in the plasma after 21 and 60 days of treatment. Besides, the coadministration of A. sativa has decreased the activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and increased transaminase activities after 21 and 60 days of treatment. On the other hand, this cereal has restored the enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH) as well as the elevated thiobarbituric acid reactive substances (AOPP and PCO) to near-normal values. The beneficial effects of this cereal were confirmed by a histological study of the liver and uterus of all previous cited groups. Our finding emphasized the antioxidant and antilipidemic effect of oat grain part, suggesting the use of this cereal in the prevention of liver and uterus diseases that occurred in postmenopausal women.

Mangiferin Inhibits Inflammation and Cell Proliferation, and Activates Proapoptotic Events via NF-κB Inhibition in DMBA-Induced Mammary Carcinogenesis in Rats.

The purpose of this study was to investigate the anti-inflammatory, antiproliferatiive, and proapoptotic molecular mechanisms of mangiferin (MGN) against mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA). Mammary cancer in rats was induced by single-dose subcutaneous injection of 0.5 ml DMBA (80 mg/kg in sesame oil) in the mammary gland. Increased tumor incidence and volume and other tumorigenic properties were observed. Further, we observed in these rats reduced antioxidant enzyme activity and elevated thiobarbituric acid reactive substance (TBARS) levels in plasma and tissues. DMBA-induced rats shows enhanced expression of the inflammatory markers NF-κBp65, COX-2, and iNOS and proliferation of PCNA and Cyclin D1, and overexpression of the antiapoptotic marker Bcl-2. Mangiferin (100 mg/kg body weight), administered orally once per day, significantly enhanced (p < 0.05) antioxidant levels and reduced TBARS levels. Moreover, MGN inhibited NF-κBp65 nucleus transcriptional activation, thereby suppressing inflammation and cell proliferation, and it increased proapoptotic proteins. Apoptosis was confirmed by TUNEL assay. In summary, MGN suppressed DMBA-induced mammary carcinogenesis through enhanced antioxidant levels, NF-κB inhibition, and positive regulation of apoptotic signals.

Nephroprotective role of bromelain against oxidative injury induced by aluminium in rats

The present study was designed to investigate the nephroprotective effect of bromelain against oxidative stress stimulated by aluminium chloride in rats. Rats were grouped as follows; group one was used as control while groups 2, 3 and 4 were treated orally with bromelain (250 mg/kg, daily), aluminium chloride (AlCl3; 34 mg/kg BW, every other day) and bromelain plus AlCl3 for 30 days, respectively. Administration of AlCl3 caused a significant reduction in rats’ body and kidney weights, and increased Al accumulation in kidney tissue. Also, AlCl3 treatment elevated thiobarbituric acid reactive substances, hydrogen peroxide, kidney functions biomarkers levels and lactate dehydrogenase activity. While enzymatic (SOD, CAT, GPx, GR, GST) and non-enzymatic (GSH) antioxidants, protein content, and alkaline phosphatase activity were significantly decreased. In addition, significant alterations in lipid and protein profiles were detected. Furthermore, histopathological and immunohistochemical variations were seen in kidney sections supporting the obtained biochemical changes. Otherwise, rats supplemented with bromelain singly declined lipid peroxidation and improved most of the studied parameters. Moreover, rats pretreated with bromelain followed by AlCl3 intoxication showed significant alleviation in lipid peroxidation, antioxidant status and biochemical indices with respect to AlCl3 treated group. Conclusively, bromelain has beneficial protective effects and has the capability to counteract the toxic influence of AlCl3. So, bromelain might represent a novel approach in the therapy of metal toxicity because of its antioxidant and chelating properties.

Saliva profiles in children with congenital heart disease.

The low salivary pH and buffering capacity are caused by using heart failure medications. For this reason oral health should be supported in cardiac patients, it is necessary that they attend dental clinics for regular follow up. The aim of this study is to evaluate the relationship between the salivary oxidative stress markers and salivary pH, salivary buffering capacity, salivary flow rate and dental caries of children with congenital heart disease (CHD). This cross sectional study was carried out with 42 CHD and 42 healthy children. The participants' gender, age, general health and medications, and caries scores (dfs/ DMFS) were written down, then their unstimulated saliva samples were collected. These specimens were evaluated in terms of the salivary secretion rate, salivary buffering capacity, pH, protein levels, superoxide dismutase (SOD), ferric reducing antioxidant power (FRAP), the thiobarbituric acid reactive substances (TBARS), protein carbonyl, protein thiols, total sialic acid. Both groups showed caries at similar levels. The salivary pH and buffering capacity were significantly less in the children with CHD than in the controls. The levels of TBARS and protein carbonyl were significantly higher in the children with CHD than in the controls. There was not any significant difference relating to the mean salivary secretion rate, protein levels, SOD, FRAP, protein thiols and total sialic acid. The elevated TBARS and protein carbonyl levels in the patients with CHD were observed as an indicator of the free radical damage leading to oxidative stress.

Role of cinnamon oil against acetaminophen overdose induced neurological aberrations through brain stress and cytokine upregulation in rat brain

Acetaminophen (APAP) is a well-known antipyretic and analgesic medicine. It is safe at therapeutic suggested level while overdose initiates oxidative stress and inflammation mediated neurochemical alteration in the brain. The aim of this study was to investigate the role of cinnamon oil (CO), which possesses potent antioxidant and anti-inflammatory activities against an overdose of APAP that induced oxidative stress and inflammation in male albino rats. APAP treated rats showed significant elevation of thiobarbituric acid-reactive substances (TBARS) and decreased level of GSH in brain tissue, which is recognized as a biomarker of oxidative stress. Antioxidant enzymes GPx, GR, SOD, and CAT activity was depleted in APAP group along with neurotoxicity biomarkers such as Na+-K+-ATPase and increased activity of acetylcholinesterase (AchE), monoamine oxidase (MAO), and upregulated pro-inflammatory cytokine was observed. CO significantly protected the diminished activity of the antioxidant enzyme and suppressed the upregulated cytokines in brain tissue. CO also attenuated the activity of neurotoxicity biomarker enzyme, decreased TBARS content, and an increased level of GSH. The present findings perceptibly confirmed that the nutraceutical property of CO ameliorates APAP induced oxidative stress and inflammation. Therefore, our findings suggested that CO could be an alternative nutraceutical substitute in APAP overdose poisoning.

Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model.

Earlier studies revealed the potential therapeutic values of Loranthus regularis (L. regularis). This study evaluated Loranthus regularis (L. regularis) extract systemic antidiabetic effects and benefits against diabetic hepatocellular injuries through antioxidant and anti-inflammatory pathways using the streptozotocin (STZ) model in Wistar albino rats. After diabetes induction, animals were orally treated with L. regularis extract for 4 weeks. Serum levels of glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were estimated. Furthermore, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), caspase-3, nitric oxide (NO), and prostaglandin E-2 (PGE-2) were estimated in serum. In liver, thiobarbituric acid reactive substances (TBARSs) and reduced glutathione (GSH) as well as the proinflammatory cytokines and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reeducates (GR), and glutathione-S-transferase (GST) were assayed. Finally, the degree of hepatic tissue damage was evaluated histologically. Treatment of the diabetic rats with L. regularis extract markedly reduced the elevated serum levels of glucose, ALT, AST, TC, TG, LDL, TNF-α, IL-1β, IL-6, caspase-3, NO, and PGE-2. L. regularis extract also improved serum levels of insulin and HDL. The elevated TBARS, TNF-α, IL-1β, and IL-6 levels in hepatic tissue of diabetic animals were reduced by L. regularis. Moreover, L. regularis extract significantly restored the diminished hepatic GSH level and enzymatic activities of SOD, CAT, GPx, GR, and GST in diabetic animals. The biochemical protective effects of L. regularis were associated with improved histological hepatocellular integrity and architecture. Taken together, L. regularis has therapeutic effects against diabetic-induced hepatic complications. The restored liver functions and cellular damage might be mediated through free radicals scavenging and proinflammatory cytokine inhibition.

Azadirachta indica and Ocimum sanctum leaf extracts alleviate arsenic toxicity by reducing arsenic uptake and improving antioxidant system in rice seedlings.

In the present study the potentials of aqueous extracts of the two plants, neem (Azadirachta indica) and Tulsi (Ocimum sanctum) were examined in alleviating arsenic toxicity in rice (Oryza sativa L.) plants grown in hydroponics. Seedlings of rice grown for 8days in nutrient solution containing 50μM sodium arsenite showed decline in growth, reduced biomass, altered membrane permeability and increased production of superoxide anion (O2 ·-), H2O2 and hydroxyl radicals (·OH). Increased lipid peroxidation marked by elevated TBARS (thiobarbituric acid reactive substances) level, increased protein carbonylation, alterated levels of ascorbate, glutathione and increased activities of enzymes SOD (superoxide dismutase), CAT (catalase), APX (ascorbate peroxidase) and GPX (glutathione peroxidase) were noted in the seedlings on As treatment. Exogenously added leaf aqueous extracts of Azadirachta indica (0.75mgmL-1, w/v) and Ocimum sanctum (0.87mgmL-1, w/v) in the growth medium considerably alleviated As toxicity effects in the seedlings, marked by reduced As uptake, restoration of membrane integrity, reduced production of ROS, lowering oxidative damage and restoring the levels of ascorbate, glutathione and activity levels of antioxidative enzymes. Arsenic uptake in the seedlings declined by 72.5% in roots and 72.8% in shoots, when A. indica extract was present in the As treatment medium whereas with O. sanctum extract, the uptake declined by 67.2% in roots and 70.01% in shoots. Results suggest that both A. indica and O. sanctum aqueous extracts have potentials to alleviate arsenic toxicity in rice plants and that A. indica can serve as better As toxicity alleviator compared to O. sanctum.

High dietary vitamin C intake reduces glucocorticoid-induced immunosuppression and measures of oxidative stress in vitamin C-deficient senescence marker protein 30 knockout mice.

Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.

Telluric acid ameliorates hepatic ischemia reperfusion-induced injury in rats: Involvement of TLR4, Nrf2, and PI3K/Akt signaling pathways

In past tellurium-based compounds had limited use, however, their therapeutic potential have been target of interest recently due to antioxidant and anti-inflammatory capabilities in experimental endotoxemia. Nevertheless, their potential hepatoprotective effect against ischemia reperfusion (IR) injury is still obscure. This study examined the possible hepatoprotective effect of telluric acid (TELL), one of tellurium-based compound, against the deteriorating effect hepatic IR injury in rats through directing toll like receptor-4 (TLR4) cascade, phosphoinositide 3-kinase(PI3K)/Akt axis, and nuclear erythroid-related factor-2 (Nrf-2) pathway as possible mechanisms contributed to TELL’s effect. Indeed, male Wistar rats were randomized into 3 groups: sham-operated, control IR and TELL (50 µg/kg). TELL was administrated once daily for seven consecutive days prior to the IR induction. Pretreatment with TELL attenuated hepatic IR injury as manifested by hampered plasma aminotransaminases and lactate dehydrogenase activities. Also, TELL opposed IR induced elevation in tissue expression/activity of high-mobility group box protein-1 (HMGB1), TLR4, myeloid differentiation primary-response protein 88 (MyD88), phospho-nuclear factor-kappa B p65 (p-NF-κB p65), phospho-mitogen activated protein kinasep38 (p-MAPKp38) and tumor necrosis factor-alpha (TNF-α). Moreover, TELL reduced the elevated thiobarbituric acid reactive substances along with increased both Nrf-2 and endothelial nitric oxide synthase (eNOS) protein expression, beside replenishment of hepatic reduced glutathione. In addition, TELL induced obvious upregulation of p-PI3K and p-Akt protein expressions together with restoration of histopathological changes in IR injury. In conclusion, TELL purveyed conceivable novel hepatoprotective mechanisms and attenuated events associated with acute hepatic injury via inhibition of TLR4 downstream axis and activation of Nrf-2 and PI3K/Akt signaling cascades. Thus, TELL may provide a novel therapeutic potential for complications of hepatic IR injury.

Seaweed Supplementation Enhances Maximal Muscular Strength and Attenuates Resistance Exercise-Induced Oxidative Stress in Rats.

We investigated the effect of chronic seaweed (Gracilaria asiatica) supplementation on maximal carrying capacity, muscle mass, and oxidative stress in rats following high-intensity resistance exercise (RE). Forty Sprague-Daley rats were equally categorized into control, exercise, seaweed, and exercise plus seaweed (ES) groups. Rats in respective groups performed RE (once per 2 days) or received seaweed (250 mg/kg bodyweight, orally) for 10 weeks. Results showed that seaweed consumption in combination with RE significantly (p < 0.05) increased maximal weight carrying capacity compared to RE alone. FHL muscle mass was significantly higher in both exercise and ES groups. Notably, high-intensity RE-induced lipid peroxidation, as evidenced by elevated thiobarbituric acid reactive substances (TBARS) in muscle, was substantially diminished (p < 0.05) by seaweed treatment. This antioxidative effect of seaweed was further represented by augmented superoxide dismutase activity and glutathione levels in seaweed groups. We noticed increased insulin concentrations and HOMA-IR, while the fasting blood glucose levels remained stable in seaweed and ES groups. Our findings conclude that seaweed in combination with RE enhanced maximal carrying strength and attenuated oxidative stress through improved antioxidant capacity. Seaweed could be a potential nutritional supplement to boost performance and to prevent exercise-induced muscle damage.

Migraine and subclinical atherosclerosis: endothelial dysfunction biomarkers and carotid intima-media thickness: a case-control study.

Migraine is a common neurovascular disease associated with vascular risks, especially in young adult females, but the mechanism underlying these associations remains unknown. This study evaluated the relationships between plasma endothelial dysfunction biomarkers and carotid intima-media thickness (IMT) in young adult females with migraine. This case-control study included 148 female patients (age range: 18-50years). Migraine was diagnosed according to the International Headache Society-IIIb criteria. Endothelial dysfunction biomarkers, such as von Willebrand factor (vWF), C-reactive protein (CRP), homocysteine, total nitrate/nitrite concentration, and thiobarbituric acid-reactive substances (TBARS), were evaluated in plasma. Carotid IMT was measured by a radiologist with sonography. The CRP, TBARS, vWF, and IMT levels were increased in the migraine compared with the control group (p < 0.001, p = 0.02, p < 0.001, and p < 0.001, respectively). After adjusting for confounders, multiple linear regression analysis revealed that systolic arterial blood pressure, CRP, vWF, TBARS, and right and left internal carotid artery (ICA) IMT were independently positively correlated with migraine (p < 0.01, p = 0.004, p = 0.023, p = 0.024, p = 0.032, and p = 0.048, respectively). Multiple logistic regression analysis revealed that right ICA IMT was independently associated with ergotamine and triptan and left ICA IMT was independently associated with ergotamine (p = 0.013, p = 0.026, and p = 0.017, respectively). In addition, significant correlations were found between LDL lipoprotein and carotid IMT in the migraine group (p < 0.05). Carotid IMT enhancement and elevated TBARS, vWF, and CRP levels in migraine subjects during a migraine attack could be regarded as consequences of migraine attack pathophysiology. The independent associations between triptan and ergotamine consumption and enhanced carotid IMT suggest that repeated use of these vasoconstrictive antimigraine agents may have additional effects on carotid IMT.

Potential immunomodulatory and antioxidant effects of walnut Juglans regia vegetable oil against lead-mediated hepatic damage and their interaction with lipase activity in rats.

Environmental pollutants, particularly lead, pose a serious threat to human and animal health that causes disturbances of several functions, including hepatotoxicity. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. This study was carried out to investigate the protective efficacy of Juglans regia vegetable oil (JRVO) against the hepatotoxicity induced by lead. To achieve this aim, adults male rats were treated for 10 days with Pb (0.344 g/kg bw) associated or not with JRVO (0.9 g/kg bw). The rats intoxicated by lead exhibited oxidative stress determined by TBARS, protein carbonyls, liver tumor necrosis factor-α (TNF-α), caspase-3, and antioxidant status: SOD, CAT, GPx, and GSH. Administration of lead increased the levels of plasma hepatic markers (AST, ALT, LDH) and bilirubin, the lipid profiles (total cholesterol, triglycerides, VLDL-Ch, LDL-Ch levels, TBARS, NOx, and PCO), the plasmatic lipase activity and the inflammatory markers, while the plasmatic ALP decreased. Coadministration of JRVO restored all the hepatic markers, the lipid profiles and the antioxidants to near-normal values and lowered the plasmatic lipase activity as well as the elevated thiobarbituric acid reactive substances. Hepatic histological studies confirmed the beneficial role of JRVO through the amelioration of all biochemical parameters. Our results suggest that Juglans regia vegetable oil contains promising substances to counteract the lead intoxication and may be efficient in the prevention of hepatotoxicity complications.

Antioxidant effects on the intracerebroventricular galactose damage in rats

We investigated the effects of the intracerebroventricular infusion of galactose and the influence of pretreatment with antioxidants on oxidative stress parameters and acethylcholinesterase (AChE) activity in the brain of 60-day-old Wistar rats (6 per group). The animals were divided into naïve group (did not undergo surgery); procedure group (only underwent surgery); sham group (underwent surgery and received 5 μL saline) and galactose group (received 5 μL of galactose solution (5.0 mM) by intracerebroventricular injection), and were killed by decapitation after 1 h. Other groups were pretreated daily for 1 week with saline (sham and galactose groups) or antioxidants, α-tocopherol (40 mg/kg) plus ascorbic acid (100 mg/kg, i.p.) (antioxidants and galactose + antioxidants groups). Twelve hours after the last antioxidants injection, animals received an intracerebroventricular infusion of 5 μL of galactose solution (galactose and galactose + antioxidants groups) or saline (sham and antioxidants groups) and were sacrificed 1 h later. Galactose elevated thiobarbituric acid reactive substances (TBA-RS), protein carbonyl content and glutathione peroxidase (GSH-Px) activity and decreased total sulfhydryl content and catalase (CAT) activity in the cerebral cortex. In the hippocampus, galactose enhanced TBA-RS, decreased total sulfhydryl content and increased AChE activity, while in the cerebellum it decreased total sulfhydryl content and increased CAT and superoxide dismutase (SOD) activities. Pretreatment with antioxidants prevented the majority of these alterations, indicating the participation of free radicals in these effects. Thus, intracerebroventricular galactose infusion impairs redox homeostasis in the brain; the administration of antioxidants should be considered as an adjuvant therapy to specific diets in galactosemia.

Gastroprotective Effects of Sulphated Polysaccharides from the Alga Caulerpa mexicana Reducing Ethanol-Induced Gastric Damage.

The development of the gastric lesion is complex and the result of the imbalance between aggressive and protective factors, involving the generation of free radicals and disturbance in nitric oxide (NO) production. Sulphated polysaccharides (SP), from marine algae, are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of SP from the green marine alga Caulerpa mexicana (Cm-SP) in ethanol-induced gastric damage models in mice. Cm-SP (2, 20, or 200 mg/kg), administered p.o., significantly reduced gastric damage, and these effects were inhibited through pretreatment with indomethacin. Cm-SP (200 mg/kg) prevented the ethanol-induced decline in glutathione and restored its normal level. Moreover, it was able to normalize the elevated thiobarbituric acid reactive substance levels. However, Cm-SP did not show any significant effects on NO2/NO3 level, when compared to the ethanol group. The pretreatment with L- NAME induced gastric mucosal damage and did not inhibit the gastroprotective effect of Cm-SP (200 mg/kg). In conclusion, the gastroprotective effects of Cm-SP in mice involve prostaglandins and reduction in the oxidative stress and are independent of NO.

Opposing Effects of Oxygen Regulation on Kallistatin Expression: Kallistatin as a Novel Mediator of Oxygen-Induced HIF-1-eNOS-NO Pathway.

Oxidative stress has both detrimental and beneficial effects. Kallistatin, a key component of circulation, protects against vascular and organ injury. Serum kallistatin levels are reduced in patients and animal models with hypertension, diabetes, obesity, and cancer. Reduction of kallistatin levels is inversely associated with elevated thiobarbituric acid-reactive substance. Kallistatin therapy attenuates oxidative stress and increases endothelial nitric oxide synthase (eNOS) and NO levels in animal models. However, kallistatin administration increases reactive oxygen species formation in immune cells and bacterial killing activity in septic mice. High oxygen inhibits kallistatin expression via activating the JNK-FOXO1 pathway in endothelial cells. Conversely, mild oxygen/hyperoxia stimulates kallistatin, eNOS, and hypoxia-inducible factor-1 (HIF-1) expression in endothelial cells and in the kidney of normal mice. Likewise, kallistatin stimulates eNOS and HIF-1, and kallistatin antisense RNA abolishes oxygen-induced eNOS and HIF-1 expression, indicating a role of kallistatin in mediating mild oxygen's stimulation on antioxidant genes. Protein kinase C (PKC) activation mediates HIF-1-induced eNOS synthesis in response to hyperoxia/exercise; thus, mild oxygen through PKC activation stimulates kallistatin-mediated HIF-1 and eNOS synthesis. In summary, oxidative stress induces down- or upregulation of kallistatin expression, depending on oxygen concentration, and kallistatin plays a novel role in mediating oxygen/exercise-induced HIF-1-eNOS-NO pathway.

The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form

ABSTRACTWelding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase—LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity. Betaine supplementation at 250 mg/kg/day in all study rats groups attenuated stress indices, and corticosterone and TBARS serum levels, and simultaneously stimulated increase of polymorphonuclear cells in BALF of rats. The study confirmed deleterious effect of transitory metals and particles during experimental inhalation exposure to welding dusts, evidenced in the lungs and brain by increased levels of total protein, higher cellular influx, rise of LDH in BALF, elevated TBARS and increased corticosterone in serum of rats. Our result confirm also the hypothesis about the effect of the welding dusts on the oxidative stress responsible for disturbed systemic homeostasis and impairment of calcium regulation.

Nephro-protective action of P. santalinus against alcohol-induced biochemical alterations and oxidative damage in rats.

The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na+/K+-ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage.

The in vitro effect of temperature on motility and antioxidant response of common carp Cyprinus carpio spermatozoa

The effect of temperature on Cyprinus carpio spermatozoa in vitro was investigated with spermatozoa activated at 4, 14, and 24°C. At 30s post-activation, motility rate was significantly higher at 4°C compared to 14 and 24°C, whereas highest swimming velocity was observed at 14°C. The thiobarbituric acid-reactive substance (TBARS) content was significantly higher at 14°C and 24°C than at 4°C in motile spermatozoa. No significant differences in catalase and superoxide dismutase activity relative to temperature were observed. This study provides new information regarding effect of temperature on lipid peroxidation intensity and spermatozoon motility parameters in carp. The elevation of TBARS seen at higher temperatures could be due to inadequate capacity of antioxidant enzymes to protect the cell against the detrimental effects of oxidative stress induced by higher temperatures.

Anti-diabetic and anti-oxidative activity of fixed oil extracted from Ocimum sanctum L. leaves in diabetic rats.

Ocimum sanctum L. (OS) leaves have been shown to exert diverse potential benefits in a variety of stress conditions. The present study was conducted to elucidate the effects of the fixed oil extracted from OS leaves on the blood glucose levels and serum lipid profile of streptozotocin-induced diabetic rats. In addition, the anti-oxidative activity of OS leaves to protect various organs including the liver, kidney and heart was investigated. The fixed oil of the OS leaves was extracted using hexane, and the various fatty acid contents of the oil were determined using gas chromatography-mass spectrometry. Male Wistar rats were allocated into three groups (n=7 per group): Normal control rats, diabetic rats and diabetic rats fed daily with the fixed oil for three weeks. The results showed that α-linolenic acid was the primary fatty acid contained in the fixed oil of OS. After 3 weeks of diabetic induction, the rats exhibited increased blood glucose levels and serum lipid profile, in addition to elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase MB subunit (CK-MB), creatinine and blood urea nitrogen (BUN). The fixed oil significantly decreased the elevated levels of blood glucose, the serum lipid profile and the levels of serum creatinine and BUN (P<0.001), without exerting significant effects on the elevated serum levels of AST, ALT, LDH and CK-MB. Furthermore, the fixed oil increased the diabetically-reduced levels of serum insulin and decreased the rat kidney weight. Fixed oil suppressed the elevated thiobarbituric acid reactive substances (TBARS) level and increased the activity of various antioxidative enzymes in the rat renal tissue. By contrast, the fixed oil had no effect on the elevated TBARS level and the inhibited activity of the antioxidative enzymes in the rat liver and cardiac tissues. Histopathological results indicated that the fixed oil preserved the renal tissue against oxidative stress in diabetes. In summary, the results of the present study suggest that the fixed oil extracted from OS leaves exerted anti-hyperglycemic, anti-hyperlipidemic and free radical scavenging effects in diabetic rats, thus providing renal protection against diabetes. The α-linolenic acid contained in the fixed oil may be responsible for these effects.