Effect of Kombucha,a fermented black tea in attenuating oxidative stress mediated tissue damage in alloxan induced diabetic rats

Diabetic complications associated with increased oxidative stress can be suppressed by antioxidants. In the present study we investigated the antidiabetic and antioxidant effects of Kombucha (KT), a fermented black tea, in comparison to that of unfermented black tea (BT), in ALX-induced diabetic rats. ALX exposure lowered the body weight and plasma insulin by about 28.12% and 61.34% respectively and elevated blood glucose level and glycated Hb by about 3.79 and 3.73 folds respectively. The oxidative stress related parameters like lipid peroxidation end products (increased by 3.38, 1.7, 1.65, 1.94 folds respectively), protein carbonyl content (increased by 2.5, 2.35, 1.8, 3.26 folds respectively), glutathione content (decreased by 59.8%, 47.27%, 53.69%, 74.03% respectively), antioxidant enzyme activities were also altered in the pancreatic, hepatic, renal and cardiac tissues of diabetic animals. Results showed significant antidiabetic potential of the fermented beverage (150 mg lyophilized extract/kg bw for 14 days) as it effectively restored ALX-induced pathophysiological changes. Moreover, it could ameliorate DNA fragmentation and caspase-3 activation in the pancreatic tissue of diabetic rats. Although unfermented black tea is effective in the above pathophysiology, KT was found to be more efficient. This might be due to the formation of some antioxidant molecules during fermentation period.     

Pyritinol reduces nociception and oxidative stress in diabetic rats

The purpose of this study was to assess the antinociceptive and antiallodynic effect of pyritinol as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral acute administration of pyritinol (50-200 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. Moreover, prolonged administration of pyritinol (12.5-50 mg/kg, every 2 days for 2 weeks) reduced formalin-induced nociception. 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) or indomethacin (a non-selective cycloxygenase inhibitor, 5 mg/kg, i.p.), blocked the pyritinol-induced antinociception in diabetic rats. Given alone ODQ, naltrexone or indomethacin did not modify formalin-induced nociception in diabetic rats. Oral acute (200 mg/kg) or prolonged (25 mg/kg, every 2 days for 2 weeks) administration of pyritinol significantly reduced streptozotocin-induced changes in free carbonyls, dityrosine, malondialdehyde and advanced oxidative protein products. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of pyritinol (50-200 mg/kg) reduced tactile allodynia in diabetic rats. Results indicate that pyritinol is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that activation of guanylyl cyclase and the scavenger properties of pyritinol, but not improvement in glucose levels, play an important role in these effects.     

N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats

Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5 mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50 mg/kg b.w.; p.o.) for 7 days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.     

Diabetes mellitus: oxidative stress and wine

SUMMARY

This review focuses on the link between diabetes mellitus and oxidative stress and, in particular, on the role that moderate wine consumption may play in preventing diabetic complications and the onset of diabetes. With this aim, a search of PubMed was carried out for literature published up to March

In diabetes mellitus, oxidative stress results both from exposure to hyperglycaemia through glycoxidation and sorbitol system activation, and from functional limitation of the hexose monophosphate shunt, leading to a decrease in glutathione synthesis.

Oxidative stress alters the plasma lipoprotein profile (particularly low- density lipoproteins), the coagulative parameters (with an increased thrombotic risk), the endothelium (with a decrease in prostacyclin synthesis and an increase of thromboxane production) and the cell membranes (which undergo peroxidation). In diabetic patients, an altered oxidative pattern is present not only in the fasting state but also especially after food intake. In particular, food intake induces a decrease

in the total radical-trapping antioxidant parameter (TRAP) and an elevation of hydroperoxides and thiobarbituric acid reactive substances (TBARS).

Previously several clinical trials tried to improve the diabetic oxidative status using α-tocopherol, ascorbic acid and β-carotene supplementation. Some authors found, in normal subjects, a reduction of hydroperoxides postprandially when the meal included red wine. Other authors showed that the oxidative pattern present in type 2 diabetic patients was mitigated by red wine. These actions may reduce cardiovascular risk. Moreover, an inverse relationship was observed between alcohol consumption and the incidence of type 2 diabetes; this relationship was valid for a light to moderate intake and it seemed to depend on drinking regularly and to be independent of the type of alcoholic beverage.

In conclusion, moderate and regular wine consumption could ameliorate the diabetic oxidative status. This lifestyle measure might contribute to preventing diabetic complications and the onset of diabetes.     

Efficacy of royal jelly against the oxidative stress of fumonisin in rats.

Fumonisins (FB) are mycotoxins produced by Fusarium verticillioides, frequently associated with corn. It produces toxicity, including teratogenicity, equine leukoencephalomalacia, porcine pulmonary edema, hepatic or renal damage in most animal species and perturb sphingolipid metabolism. The aim of the present study was to evaluate the protective effects of royal jelly (RJ) against FB toxicity. Sixty male Sprague-Dawley rats were divided into six treatment groups including the control group; group fed FB-contaminated diet (200mg/kg diet) and the groups treated orally with RJ (100 or 150mg/kg body weight) with or without FB for 3 weeks. FB alone decreased body weight gain, feed intake, GPX and SOD. Whereas it increased in ALT, AST, triglycerides, cholesterol, HDL, LDL, createnine and uric acid levels. Animals received FB showed severe histological and histochemical changes in liver and kidney tissues. Cotreatment with FB plus RJ resulted in a significant improvement in all the tested parameters and the histological and histochemical pictures of the liver and kidney. These improvements were pronounced in animals fed FB-contaminated diet plus the high dose of RJ. It could be concluded that RJ have a protective effects against FB toxicity and this protection was dose dependent.     

Toxicity of copper intake: lipid profile, oxidative stress and susceptibility to renal dysfunction

The present study was carried out to investigate the effects of copper (Cu) intake on lipid profile, oxidative stress and tissue damage in normal and in diabetic condition. Since diabetes mellitus is a situation of high-risk susceptibility to toxic compounds, we examined potential early markers of Cu excess in diabetic animals. Male Wistar rats, at 60-days-old were divided into six groups of eight rats each. The control(C) received saline from gastric tube, the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu⁺⁺–CuSO₄, gastric tube), no-diabetic with Cu-60 mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and diabetic high-Cu(DCu-60). Diabetes was induced by an ip injection of streptozotocin (60 mg/kg). After 30 days of treatments, no changes were observed in serum lactate dehydrogenase, alanine transaminase and alkaline phosphatase, indicating no adverse effects on cardiac and hepatic tissues. D-rats had glucose intolerance and dyslipidemic profile. Cholesterol and LDL-cholesterol were higher in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60 rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was increased and GSH-Px was decreased, while no alterations were observed in SOD and catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose, creatinine and albumin. In conclusion, Cu intake at high concentration induced adverse effects on lipid profile, associated with oxidative stress and diminished activities of antioxidant enzymes. Diabetic animals were more susceptible to copper toxicity. High Cu intake induced dyslipidemic profile, oxidative stress and kidney dysfunction in diabetic condition. Copper renal toxicity was associated with oxidative stress and reduction at least, one of the antioxidant enzymes.     

Influence of polyphenolic extracts from Enydra fluctuans on oxidative stress induced by acephate in rats

Acephate, an organophosphorus pesticide, has been proved to play an important role in tissue damage by inducing oxidative stress through the release of free radicals. The aim of this study was to evaluate the protective effect of the plant phenolic compounds present in Enydra fluctuans against acephate toxicity based on lipid peroxidation and antioxidant enzymes profile in rats. An oral dose of acephate at 30 mg/kg of body weight has been given against the extracts containing 20 mg of polyphenolic compounds (expressed as gallic acid equivalents)/kg body weight for 14 days. The results showed that under the influence of the pesticides, there was significant decrease in the activities of the antioxidant enzymes SOD, Catalase and Glutathione peroxidase (GPx) and an increase in the non-enzymatic Glutathione, with respect to the normal and the plant extract gavaged groups. Also that there was an increase in the plasma and erythrocyte membrane lipid peroxidation levels in the pesticide treated group compared to the normal or the group treated with the plant extract. The present study thus gives an insight into the ill-effects of this organophosphate and the protective role of plant polyphenols in minimizing those effects.     

Early oxidative stress in testis and epididymal sperm in streptozotocin-induced diabetic mice: its progression and genotoxic consequences

Experimental induction of diabetes mellitus in animal models using chemical diabetogens is demonstrated to impair testicular function progressively leading to decreased fertility. Although, both steroidogenic and spermatogenic dysfunctions have been reported, the role of oxidative stress mechanism/s has been less understood. We have investigated the induction of oxidative damage during early diabetic phase in testis and epididymal sperm (ES) in mice administered an acute dose of streptozotocin (STZ). Our results show enhanced lipid peroxidation in testis (cytosol and mitochondria) and ES and increased ROS production as early as 5 days. Further, significant perturbations in the activities of antioxidant enzymes in testis/ES and enhanced protein carbonyl content were suggestive of increased oxidative stress during early diabetic phase. STZ-induced oxidative damage in both compartments was amenable for attenuation by treatment with oral supplements of either ascorbic acid (10 mg/(kg(bw) day)) or taurine (1 g/(kg(bw) day)). Furthermore, the oxidative impairments in testis/ES were persistent during the progressive phase (as measured at 2 and 4 weeks of sampling) and were associated with significant increase DNA damage (testis) and higher incidence of abnormal sperms. Interestingly, mating of STZ treated males sequentially for a period of 5 weeks with virgin untreated females resulted in a significant increase in the male-mediated dominant lethal-type mutations during the first 3 weeks, indicating a stage-specific genotoxic effect on post-meiotic germ cells. Based on the occurrence of oxidative impairments in STZ-treated mice both during both early and progressive phase, it is hypothesized that oxidative stress mechanisms may be wholly or in part contribute towards the development of testicular dysfunction and degeneration under situations of experimentally induced diabetes in animal models.     

Effect of long term, non cholesterol lowering dose of fluvastatin treatment on oxidative stress in brain and peripheral tissues of streptozotocin-diabetic rats

One of the main goals of treatment of diabetes mellitus is to prevent its complications. Oxidative stress is universal in diabetes, being ultimately involved with the development complications. As a result of hyperglycemia, reactive oxygen/nitrogen species are produced in various tissues that leads to tissue damage with lipid peroxidation and protein oxidation, along with disruption in cellular homeostasis and accumulation of damaged molecules. Hence, supplementation with antioxidant compounds may offer some protection against diabetic complications. The pleiotropic effects of statins, including antioxidant and anti-inflammatory properties, represent an area of great interest in prevention and therapy of cardiovascular and neurological disorders. Using biomarkers of oxidative stress, in this study we examined the effect of non cholesterol lowering dose, long term fluvastatin treatment on oxidative stress in streptozotocin-diabetic rats. Experiments were conducted in 24 Wistar adult male rats. Diabetic and non-diabetic rats were treated orally for 6 months with fluvastatin (2 mg/kg/day, p.o) starting one week after streptozotocin injection (55 mg/kg, i.p.), (preventive study). In brain, heart, liver, pancreas and kidney homogenates malondialdehyde, lipid hydroperoxide, protein carbonyl content, advanced oxidation protein products, 3-nitrotyrosine levels and superoxide dismutase, catalase activities were measured. Hyperglycemia and dyslipidemia in diabetic groups remained unchanged after fluvastatin treatment. The drug act as antioxidant in the tissues. Hence, antioxidant property of fluvastatin, independent of cholesterol lowering effect, may play a role in prevention of diabetic complications. Clinical relevance of this effect of fluvastatin seems worthy of further studies.     

Chromium(VI) induces oxidative stress in the mouse brain

Potassium dichromate was given to female Swiss mice (25 mg/kg per day) orally in water for 1–3 days. Brain homogenates were prepared to evaluate the occurrence of oxidative stress in this organ through the measurement of the antioxidant defense levels, and the extent of lipid peroxidation. In addition, mitochondrial fractions were isolated from brain homogenates to determine the production of reactive oxygen species in this subcellular fraction. The administration of potassium dichromate for 3 days caused increases of 72 and 74% in superoxide dismutase and catalase activities, respectively, in the homogenates. The treatment with this metal for 3 days increased brain homogenate chemiluminescence and thiobarbituric acid-reactive substances by 34 and 29%, respectively. The brain contents of the non-enzymatic antioxidants -tocopherol and sulfhydryl groups decreased by 35 and 32%, respectively. Ascorbic acid levels were not modified by the administration of potassium dichromate. Finally, there was a significant increment in the mitochondrial production of oxidants in the brain of treated mice as compared with controls. These results suggest that chromium(VI) produces an increased formation of reactive oxygen species and brain lipid peroxidation. The increase in the antioxidant enzyme activities reflects an adaptive response against oxidative stress, while the reduction in the levels of non-enzymatic antioxidants might be due to their reaction with reactive oxygen species generated during the metabolism of chromium(VI).     

Effect of treatment with vitamin D plus calcium on oxidative stress in streptozotocin-induced diabetic rats

Background

In diabetes mellitus, uncontrolled hyperglycemia has been reported to induce oxidative stress, which may lead to health complications. Vitamin D, however, acts as a non-enzymatic antioxidant to protect cells against oxidative stress and damage.

Upregulation of insulin secretion and downregulation of pro-inflammatory cytokines,oxidative stress and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats by Pseuduvaria monticola bark extract

The current study aimed to ascertain the antidiabetic potential of Pseuduvaria monticola bark methanolic extract (PMm) using in vitro mechanistic study models. In particular, the study determined the effect of PMm on cellular viability, 2-NBDG glucose uptake, insulin secretion, and NF-κB translocation in mouse pancreatic insulinoma cells (NIT-1). Furthermore, in vivo acute toxicity and antidiabetic studies were performed using streptozotocin (STZ)-induced type 1 and STZ-nicotinamide-induced type 2 diabetic rat models to evaluate various biochemical parameters and markers of oxidative stress and pro-inflammatory cytokines. Five isoquinoline alkaloids and three phenolic compounds were tentatively identified in the PMm by LC/MS Triple TOF. The study results showed that PMm is non-toxic to NIT-1 cells and significantly increased the glucose uptake and insulin secretion without affecting the translocation of NF-κB. Moreover, the non-toxic effects of PMm were confirmed through an in vivo acute toxicity study, which revealed that the serum insulin and C-peptide levels were significantly upregulated in type 2 diabetic rats and that no significant changes were observed in type 1 diabetic rats. Similarly, PMm was found to downregulate the levels of oxidative stress and pro-inflammatory cytokines in type 2 diabetic rats by alleviating hyperglycemia. Therefore, we conclude that PMm may be developed as an antidiabetic agent for the treatment of type 2 diabetes-associated conditions.     

Enzymatic studies of cisplatin induced oxidative stress in hepatic tissue of rats

Cisplatin is an active cytotoxic agent that has proved to be successful in the treatment of various types of solid tumors. The drug-induced nephrotoxicity has been very well documented in clinical oncology. However, hepatotoxicity has been rarely characterized and paid attention to, and is the least studied. We have used rat as the model to evaluate the effect of cisplatin on liver antioxidant enzymes and to determine whether these modulations in enzymatic activities are involved in hepatotoxicity. Reports obtained from our study indicate that cisplatin increases lipid peroxidation in the treated tissue of rat. The drug is also involved in altering the thiol status of the tissue with concomitant alterations in the enzymatic antioxidants. Glutathione and glutathione reductase levels were significantly decreased after cisplatin therapy, whereas glutathione peroxidase, gamma-glutamyl transpeptidase and catalase showed a significant increase. No statistically significant change was observed in glutathione-S-transferase activity. After cisplatin treatment, cytochrome P 450 showed a significant increase, whereas cytochrome b5 was decreased. Thus, an alteration in enzymatic antioxidant status with increase in lipid peroxidation indicates that the enzymes play an important role in combating free radical induced oxidative stress on the tissue.     

An investigation of the neuroprotective effects of Curcumin in a model of Homocysteine - induced oxidative stress in the rat's brain

BACKGROUND AND THE PURPOSE OF THE STUDY: Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of them. Oxidative stress can induce neuronal damages and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study, the possible antioxidant and neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin against homocysteine (Hcy) neurotoxicity was investigated. METHODS: Curcumin (5, 15, 45 mg/kg) was injected intraperitonealy (i.p.) once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 μmol/μl) intracerebroventricular (i.c.v) injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24 hrs after the last curcumin or its vehicle injection. The cell density of hippocampus layers and apoptosis in rats' hippocampi by immunohistochical methods were also studied. RESULTS AND MAJOR CONCLUSION: Results indicated that Hcy could induce lipid peroxidation and increase Malondialdehyde (MDA) and Super Oxide Anion (SOA) levels in rat's brain. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, curcumin decreased MDA and SOA levels significantly and improved learning and memory in rats. On the other hand Hcy could induce cell death and apoptosis in rats' hippocampi which was inhibited by curcumin. These results suggest that Hcy may induce lipid peroxidation in rat's brain. and polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against Oxidative stress.     

Assessment of antidiabetogenic potential of fermented soybean extracts in streptozotocin-induced diabetic rat

Most of the available drugs for the treatment of diabetes mellitus (DM) produce detrimental side effects, which has prompted an ongoing search for plant with the antidiabetic potential. The present study investigated the effect of soybean extracts fermented with Bacillus subtilis MORI, fermented soybean extracts (BTD-1) was investigated in streptozotocin (STZ)-induced diabetic rats. The possible effects of BTD-1 against hyperglycemia and free radical-mediated oxidative stress was investigated by assaying the plasma glucose level and the activity of enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). A significant increase in the levels of both plasma glucose and reactive oxygen species (ROS) was observed in the diabetic rats when compared to normal control group. After administration of BTD-1 (500 and 1000 mg/kg/day), the elevated plasma glucose level was significantly reduced while the plasma insulin level and the activities of SOD, GSH-Px, CAT and MDA were significantly increased. The results suggest that administration of BTD-1 can inhibit hyperglycemia and free radical-mediated oxidative stress. The administration of BTD-1 also inhibited the contractile response by norepinephrine (10⁻¹⁰–10⁻⁵ M) in the presence of endothelium, and caused significant relaxation by carbachol (10⁻⁸–10⁻⁵ M) in rat aorta. These findings indicate that BTD-1 improves vascular functions on STZ-induced diabetic rats. Therefore, subchronic administration of BTD-1 could prevent the functional changes in vascular reactivity in STZ-induced diabetic rats. The collective findings support that administration of BTD-1 may prevent some diabetes-related changes in vascular reactivity directly and/or indirectly due to its hypoglycaemic effect and inhibition of production of ROS.     

Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: Role of oxidative stress and caspase-3

Cadmium (Cd) is an environmental and industrial pollutant that can induce a broad spectrum of toxicological effects that affect various organs in humans and experimental animals. This study aims to investigate the effect of betaine supplementation on cadmium-induced oxidative impairment in rat kidney. The animals were divided into four groups (n = 10 per group): control, cadmium, betaine and betaine + cadmium (1) saline control group; (2) cadmium group in which cadmium chloride (CdCl₂) was given orally at a daily dose of 5 mg/kg body weight for four weeks; (3) betaine group, in which betaine was given to rats at a dose of 250 mg/kg/day, orally via gavage for six weeks; (4) cadmium + betaine group in which betaine was given at a dose of 250 mg/kg/day, orally via gavage for two weeks prior to cadmium administration and concurrently during cadmium administration for four weeks. Cadmium nephrotoxicity was indicated by elevated blood urea nitrogen (BUN) and serum creatinine levels. Kidneys from cadmium-treated rats showed an increase in lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) concentration and reductions in total antioxidant status (TAS), reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase concentration (SOD) and catalase activity. Caspase-3 activity, a marker of DNA damage was also elevated in renal tissues of cadmium-treated rats. Pre-treatment of rats with betaine substantially attenuated the increase in BUN and serum creatinine levels. Betaine also inhibited the increase in TBARS concentration and reversed the cadmium-induced depletion in total antioxidant status, GSH, GSH-Px, SOD and catalase concentrations in renal tissues. Renal caspase-3 activity was also reduced with betaine supplementation. These data emphasize the importance of oxidative stress and caspase signaling cascade in cadmium nephrotoxicity and suggest that betaine pretreatment reduces severity of cadmium nephrotoxicity probably via antioxidant action and suppression of apoptosis.     

Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain

Silymarin (SM), the active complex of milk thistle, is a lipophilic fruit extract and is composed of several isomer flavonolignans. Flavonoids are antioxidants found molecules capable of intercepting reactive oxygen species (ROS). The oxidative stress (OS) is caused by imbalance between antioxidant defenses and production of ROS causing oxidative damage to macromolecules. Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. This study evaluated the effect of SM on biochemical parameters that evaluate OS in aged and young rat brain. For measures of OS were used measures of total oxyradical scavenging capacity (ACAP) through the concentration of ROS by fluorescence, lipid peroxidation (LPO), via FOX and TBARS, proteins oxidation by Western blot (WB). Rats were treated with SM at doses of 200 and 400 mg/kg/day (SM200 and SM400). The LPO analyzed through FOX was increased in the hippocampus of aged animals treated with SM400, but in the cortex of young and aged, the highest dose of SM decreased LPO analyzed through TBARS. Both doses have seemed most effective in the reduction of oxidized proteins in aged brain. These results suggest that SM may contribute to the prevention of aged-related and pathological degenerative processes in the brain.     

Role of melatonin in reducing hypoxia-induced oxidative stress and morphological changes in the liver of male mice

Oxygen deficiency during critical illness may cause profound changes in cellular metabolism and subsequent tissue and organ dysfunction. Thus, the present study was designed to determine the effects of hypoxia and reoxygenation on the levels of lipid peroxidation and the morphological changes in the liver of male mice as well as the protective role of melatonin as an antioxidant. Two experiments were carried out in this study. Experiment I includes three groups of mice (control, hypoxic, and hypoxic + melatonin) while the experiment II includes two groups (reoxygenated and reoxygenated + melatonin). The levels of oxidized lipids were measured and the morphological changes were investigated using light and electron microscopy. In experiment I, hypoxia strongly stimulated lipid peroxidation levels (88%) while melatonin administration inhibited this increase (69%). Severe morphological changes (necrosis, dilated congested blood vessels, collection of inflammatory cells, condensed heterochromatic with irregular outlines nuclei, and mitochondrial degeneration) were detected in the liver of hypoxic mice. In experiment II, reoxygenation inhibited the levels of oxidized lipids (42%) versus hypoxic mice and some morphological changes were detected. When melatonin was given before reoxygenation, it inhibited the levels of lipid peroxidation by 66% versus hypoxic mice. Also, melatonin enhanced the recovery profile by 41% when compared with mice that reoxygenated with room air only. All morphological alterations that detected in both hypoxic and reoxygenated mice were repaired when melatonin administered. These results indicate that hypoxia and reoxygenation induce severe alterations in the liver and that melatonin exerts beneficial role in restoring tissue alterations after subjection to hypoxia.     

The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells

Deoxynivalenol (DON) is a trichothecene mycotoxin and a cereals contamination, whose cytotoxicity has been shown in animals and various cells. However, with respect to the deoxynivalenol-induced DNA damage, especially in humans, are not well understood. The aim of this study was to assess the role of oxidative stress in deoxynivalenol-induced DNA damage, using human hepatoma HepG2 cells. Exposure of the cells to DON caused significant increase of DNA migration in comet assay at concentrations of 3.75-30 μM, which suggests that DON caused DNA strand breaks. To elucidate the role of antioxidation in those effects, DNA migration was monitored by pre-treatment with hydroxytyrosol (HT) as an antioxidant in comet assay. It was found that DNA migration with pre-treatment of HT was dramatically decreased. The DNA damage induced by DON was almost completely prevented. In order to clarify the underlying mechanisms, we evaluated the level of reactive oxygen species (ROS) production with the 2,7-dichlorofluorescein diacetate (DCFH-DA) assay. Significant increase in the level of ROS was observed in HepG2 cells at a higher concentration (60 μM). The involvement of lipid peroxidation in the DNA damage of DON was confirmed by using immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), the doses being 7.5-60 μM and 3.75-15 μM, respectively. These results indicate that the DNA damage induced by DON in HepG2 cells is probably related to the oxidative stress.     

Protective role of Dodonaea viscosa extract against streptozotocin-induced hepatotoxicity and nephrotoxicity in rats

Previous investigations have shown that D. viscosa herbal extract is often used to treat a variety of diseases. Therefore, the purpose of this study was to investigate any additional potential impacts on rat liver and kidney damage induced by diabetes. Streptozotocin (STZ) (60 mg/kg/day) was given as a single dosage to cause type 1 diabetes. After then, diabetic rats received oral doses of D. viscosa for four weeks at 150 and 300 mg/kg/day. Blood, liver, and kidney tissues were collected at the end of the treatment and examined. Analysis was made of the serum lipid profile, liver, and kidney functions, as well as blood biochemistry. Moreover, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), prostaglandin E-2 (PGE-2), and nitric oxide (NO) were estimated in serum. In liver and kidney samples, thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH), as well as the pro-inflammatory cytokines and enzymatic activities of glutathione peroxidase (GPx), glutathione reeducates (GR), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were analyzed. Histological changes in liver and kidney cross-sections were also observed. Our findings demonstrated that D. viscosa dramatically decreased pro-inflammatory indicators in blood, kidney, and liver tissues as well as blood glucose, and restored insulin levels, and lipid profiles. Additionally, it significantly raises the antioxidant enzyme activity SOD, CAT, GPx, and GST, while significantly lowering TBARs levels. The above-mentioned biochemical changes that took place in tissues were further supported by histological alterations. These findings imply that D. viscosa protects against STZ-induced hyperglycemia, aberrant lipid synthesis, and oxidative stress and that these benefits may be mediated by interacting with various targets to increase the levels of antioxidant enzymes in the liver and kidneys. Its mode of action and safety for use as medicine against various metabolic problems caused by diabetes require more research.