Formation Of Lipid Peroxidation Products Research Articles

Tannic Acid Mitigates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Inflammation, Oxidative Stress, Apoptosis, and Glutamate Toxicity in Rats.

Parkinson's disease (PD), a movement disorder, is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain. The etiopathogenesis of PD involves increased oxidative stress, augmented inflammation, impaired autophagy, accumulation of α-synuclein, and α-Glutamate neurotoxicity. The treatment of PD is limited and there is a lack of agents to prevent the disease/delay its progression and inhibit the onset of pathogenic events. Many agents of natural and synthetic origin have been investigated employing experimental models of PD, mimicking human PD. In the present study, we assessed the effect of tannic acid (TA) in a rodent model of PD induced by rotenone (ROT), a pesticide and an environmental toxin of natural origin reported to cause PD in agricultural workers and farmers. Rotenone (2.5 mg/kg/day, i.p.) was administered for 28 days, and TA (50 mg/kg, orally) was administered 30 min before ROT injections. The study results showed an increase in oxidative stress, as evidenced by the depletion of endogenous antioxidants and enhanced formation of lipid peroxidation products, along with the onset of inflammation following a rise in inflammatory mediators and proinflammatory cytokines. ROT injections have also augmented apoptosis, impaired autophagy, promoted synaptic loss, and perturbed α-Glutamate hyperpolarization in rats. ROT injections also induced the loss of dopaminergic neurons subsequent to the activation of microglia and astrocytes. However, TA treatment was observed to reduce lipid peroxidation, prevent loss of endogenous antioxidants, and inhibit the release and synthesis of proinflammatory cytokines, in addition to the favorable modulation of apoptosis and autophagic pathways. Treatment with TA also attenuated the activation of microglia and astrocytes along with preservation of dopaminergic neurons following reduced loss of dopaminergic neurodegeneration and inhibition of synaptic loss and α-Glutamate cytotoxicity. The effects of TA in ROT-induced PD were attributed to the antioxidant, anti-inflammatory, antiapoptotic, and neurogenesis properties. Based on the present study findings, it can be concluded that TA may be a promising novel therapeutic candidate for pharmaceutical as well as nutraceutical development owing to its neuroprotective properties in PD. Further regulatory toxicology and translational studies are suggested for future clinical usage in PD.

Cigarette smoking and the oxidative stress induced biochemical changes

An investigation was carried out to assess the health status of cigarette smokers, oxidative stress induced changes and prevalence of smoking among smokers of different age groups in Thiruvananthapuram city, situated in the southern part of Kerala, India. The 52 male volunteers, aged between 20 and 70 years who are residents in Ulloor ward of Thiruvananthapuram Corporation in Kerala state were selected for the study. Among these 52 subjects, 36 were current smokers and 16 were non-smokers. The body weight, height and duplicate blood pressure measurements at rest were taken. Fasting blood samples were collected to determine the changes in serum biochemical parameters like total cholesterol, malondialdehyde, sodium, potassium and selected heavy metals in smokers and non-smokers. Analysis of the results show that among the total participants, 69 % were smokers and of these smokers, 41.7 % were in the age group 36- 50 years. The body weight of the smokers was found to be less than that of the nonsmokers in the same age group. The BMI of 72.2% smokers were found to be less than that of the non-smokers. 77.8 % of the smokers in the study population were hypertensive and the blood pressure increases with age. Serum total cholesterol levels in smokers were found to be higher than that of non-smokers and this excess cholesterol may get deposited in the blood vessels and causes atherosclerosis. The smokers with BMI less than 25 recorded highest cholesterol levels. Serum sodium and potassium levels in smokers were higher than that of non-smokers. The increase in serum sodium content in smokers was highly significant compared to non-smokers. Concentrations of serum malondialdehyde, the lipid peroxidation product and the heavy metals like Cu and Cd were also found to be significantly high in smokers. The studyproves that smoking enhances free radical production which results in the formation of lipid peroxidation products and degradation of macromolecules, which may lead to cell damage or death. Results of this study also indicate that there is a positive correlation between mean cadmium content and blood pressure of smokers.

Improving Grapevine Heat Stress Resilience with Marine Plant Growth-Promoting Rhizobacteria Consortia.

Amid climate change, heatwave events are expected to increase in frequency and severity. As a result, yield losses in viticulture due to heatwave stress have increased over the years. As one of the most important crops in the world, an eco-friendly stress mitigation strategy is greatly needed. The present work aims to evaluate the physiological fitness improvement by two marine plant growth-promoting rhizobacteria consortia in Vitis vinifera cv. Antão Vaz under heatwave conditions. To assess the potential biophysical and biochemical thermal stress feedback amelioration, photochemical traits, pigment and fatty acid profiles, and osmotic and oxidative stress biomarkers were analysed. Bioaugmented grapevines exposed to heatwave stress presented a significantly enhanced photoprotection capability and higher thermo-stability, exhibiting a significantly lower dissipation energy flux than the non-inoculated plants. Additionally, one of the rhizobacterial consortia tested improved light-harvesting capabilities by increasing reaction centre availability and preserving photosynthetic efficiency. Rhizobacteria inoculation expressed an osmoprotectant promotion, revealed by the lower osmolyte concentration while maintaining leaf turgidity. Improved antioxidant mechanisms and membrane stability resulted in lowered lipid peroxidation product formation when compared to non-inoculated plants. Although the consortia were found to differ significantly in their effectiveness, these findings demonstrate that bioaugmentation induced significant heatwave stress tolerance and mitigation. This study revealed the promising usage of marine PGPR consortia to promote plant fitness and minimize heatwave impacts in grapevines.

Deuterated polyunsaturated fatty acids provided protection against oxidative stress in ocular fibroblasts derived from glaucoma patients

Glaucoma is a complex neurodegenerative disease of the optic nerve that leads to irreversible sight loss. Lowering intraocular pressure (IOP) medically or surgically represents the mainstay of treatment but despite adequate treatment optic nerve function can continue to deteriorate leading to blindness. There is significant clinical and experimental evidence that oxidative stress is involved in the pathogenesis of glaucoma. Decreasing the formation of lipid peroxidation products or scavenging them chemically could be beneficial in limiting the deleterious effects of oxidative stress in glaucoma. A solution to control the susceptibility of PUFAs to noxious lipid peroxidation reactions is by regioselective deuteration. Deuterium incorporated into PUFAs at bis-allylic positions (D-PUFAs) inhibits the rate-limiting step of lipid peroxidation. In this study, we have shown that Tenon’s ocular fibroblasts from glaucoma patients have significantly increased basal oxidative stress compared to non-glaucomatous control patients. Furthermore, we have shown that deuterated polyunsaturated fatty acids (D-PUFAs) provide an enhanced rescue of menadione induced lipid peroxidation in both non-glaucomatous and glaucomatous Tenon’s ocular fibroblasts using malondialdehyde (MDA) levels as a marker. Our study suggests that D-PUFAs may provide a potentially safe and effective method to reduce cytotoxic oxidative stress in glaucoma.

Biochemical profile of the body of chickens of different directions of productivity

Scientific and practical interest is the study of indicators of metabolic processes in various genotypes birds, which is important in the clinical and physiological assessment of the birds health. Blood from cockerels of the egg direction of productivity (Russian White breed, n=19), meat and egg direction of productivity (crossbreeds of the Russian White and Cornish breeds, n=12) and broilers (Cross Ross-308, n=9) was studied at the age of 63 days. Blood bio-chemical parameters and antioxidant protection indicators were determined, correlation coef-ficients between the studied parameters were calculated. The main differences between the groups were noted in the parameters of carbohydrate-water-lipid and mineral metabolism. The maximum value of glucose concentration (15.55 mM/l, with a difference between groups pЈ0.001) was observed in the body of the meat and egg chickens, the minimum (11.95 mM/l with a difference with the group of meat and egg chickens рЈ0.001) - in broilers. In broilers blood the maximum concentration of triglycerides (0.89 mM/l) and the minimum concentration of cholesterol (2.88 mM/l) were registered in comparison with analogues with a significant dif-ference (pЈ0.01 and pЈ0.001), which indicates more intensive processes of lipid metabolism in the body associated with the formation and deposition of fat., The antioxidant protection indi-cators in broilers were less pronounced, which is manifested in the highest level of formation of lipid peroxidation products in the blood in the form of TBA-AP (4.27 mM/l at a difference of pЈ0.001 with other groups), a decrease in the concentration of ceruloplasmin (37.78 mg/l with a difference pЈ0.05 with other groups). The conducted correlation analysis made it possible to establish various and unequal trends in the relationship between biochemical parameters and AOP indicators in various directions of productivity birds. The maximum number of detected correlations (weak and moderate) was observed in the blood of egg hens. In the blood of broil-ers, a smaller number of correlations of high and very high degree was revealed. Differences in the flow of metabolic processes in the body should be taken into account when assessing the physiological and biochemical status of the organism of birds of different directions of produc-tivity. The results obtained will serve to accumulate a database of biochemical parameters of poultry blood and develop reference intervals for healthy birds of various genotypes.

Oxidative stress in the skin: Impact and related protection.

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Formation of Lipid and Protein Oxidation Products during In Vitro Gastrointestinal Digestion of Dry-Cured Loins with Different Contents of Nitrate/Nitrite Added.

The effect of nitrate/nitrite (0, 37.5, 75, and 150 mg/kg) in the dry-cured loin formulation on the formation of lipid and protein oxidation products during in vitro digestion was evaluated. Dry-cured loins formulated with nitrate/nitrite resulted in significantly less lipid and protein oxidation than uncured loins before and after simulated digestion. Compared to loins added with 0 mg/kg nitrate/nitrite, dry-cured loins with 37.5, 75, and 150 mg/kg contained a significantly lower content of conjugated dienes, malondialdehyde, carbonyls, and non-heme iron, and higher amounts of nitrosylmioglobin and thiols. During in vitro digestion, the content of conjugated dienes, malondialdehyde, and carbonyls increased, while thiol content decreased, indicating the development of lipid and protein oxidative processes. At the end of the intestinal phase, the 75 mg/kg digests had a significantly higher content of conjugated dienes, while no differences were found among the other digests. During the in vitro intestinal phase (180 and 240 min), nitrate/nitrite curing resulted in significantly lower malondialdehyde concentrations in the 37.5, 75, and 150 mg/kg loin digests than in the uncured loin digests. No significant differences were observed at the end of the intestinal digestion phase between the cured loin digests. Digests of dried loins without nitrate/nitrite addition showed higher carbonyl contents than the nitrate/nitrite cured counterparts. The loss of thiols was significantly higher in loin digests without added nitrate/nitrite than in loin digests with different amounts of curing salts. The addition of 37.5 mg/kg nitrate/nitrite in the cured loin formulation prevents the formation of lipid peroxidation products and carbonyls from protein oxidation and thiol loss during digestion

Study of the antioxidant status in patients with secondary lymphedema of the lower extremities under conservative treatment

Aim. To assess the antioxidant status in patients with secondary lymphedema of the lower extremities who undergo different types of conservative treatment.
 Methods. The study included 90 patients with secondary lymphedema of the lower extremities and 30 healthy volunteers. Group 1 participants (n=30) received compression therapy and Vitamin E at a dose of 400 IU/day, group 2 participants (n=30) compression therapy and a micronized purified flavonoid fraction 1000 mg/day, group 3 (n=30) compression therapy alone. Group 4 (n=30) comprised healthy volunteers. The level of malondialdehyde, the activity of superoxide dismutase, glutathione peroxidase, catalase, and the level of non-protein thiols (SH-groups) were determined at inclusion in the study and then after 1 and 3 months.
 Results. In patients with secondary lymphedema, the initial level of glutathione peroxidase was higher by 768.22%, catalase by 420.5%, malondialdehyde by 60%, and the level of SH-groups was lower by 65,71% compared with the group of volunteers. In the first group, there was a significant decrease of 36.1% in the level of superoxide dismutase and a significant increase of 89.9% in the level of glutathione peroxidase at the end of therapy when compared with the level after 1 month. In the second group, catalase level significantly increased by 33.3%, superoxide dismutase by 17.6%, and glutathione peroxidase by 61.3% compared to baseline values. The biochemical indicators of the endothelium significantly increased when using a combination of micronized purified flavonoid fraction and elastic compression in comparison with elastic compression alone and a combination with Vitamin E. In the third group, there were no significant differences in the levels of biochemical indicators of endothelial function.
 Conclusion. Increased formation of lipid peroxidation products along with a decrease in the activity of antioxidant systems was revealed in patients with lower extremity secondary lymphedema compared with healthy volunteers; the most effective therapy aimed at correcting endothelial cell dysfunction is the use of micronized purified flavonoid fraction and elastic compression.

Antioxidant protection in patients with pulmonary tuberculosis

The literature review summarizes the data on the classification and characteristics of the antioxidant defense system. This model combines a number of different substances. Each of the components of the antioxidant system acts in close connection with its other structural elements, harmoniously complements, and in many cases – enhances the action of each other. The functional basis of the system of antioxidant protection is formed by the glutathione system, the constituent elements of which are actually glutathione and enzymes that catalyze the reactions of its reverse transformation (oxidation ↔ reduction). Most researchers conventionally divide the system of antioxidant protection into enzymatic and non-enzymatic. The enzyme links of the antioxidant defense system include: catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione transferase and other enzymes. The non-enzymatic system includes fat-soluble vitamins A, E and K, water-soluble vitamins C and PP, biogenic amines, glutathione, carotenoids, ubiquinone, sterols. Both enzymatic and non-enzymatic antioxidant defense systems are present in the bloodstream. The activity of the enzymatic antioxidant system is very well regulated and depends on age, physiological condition, hormone dynamics, intensity of antioxidant enzyme synthesis, pH, presence of coenzymes, inhibitors, activators and other factors. The non-enzymatic part of the antioxidant system does not require as many regulators as the chemical itself - the antioxidant - reacts chemically with the radical. Only the reaction rate can change. The lungs are directly exposed to oxygen and oxidants of polluted air, they are most sensitive to oxidative damage, so they have an increased possibility of free radical reactions. Protection against the damaging effects of reactive oxygen species and free radicals is provided by anti-radical protective systems, especially the glutathione system and its enzymes. Numerous papers have obtained clinical and experimental data on the important role of free radical oxidation of lipids (FROL) and antioxidant systems (AOS) protection in the development of many diseases, including pulmonary tuberculosis (TB). The review presents modern views on the state of the system of lipid peroxidation (LPO) and antioxidant protection in TB. The main topic of the review is information on the generation of free radical compounds by different populations of leukocytes with further enhancement of LPO and secondary deepening of functional disorders. The article substantiates the feasibility of identifying LPO products as non-specific markers of aseptic inflammation in TB and the need to develop new generations of antioxidants. One of the universal mechanisms of damage to cell membranes is LPO, the excessive activation of which is normally prevented by factors of the antioxidant defense system. Membrane-bound enzymes involved in the formation of LPO products include lipoxy and cyclooxygenases. Lipoperoxidation processes change the structure and phospholipid composition of cell membranes, which negatively affects the cellular immune response due to damage to the mechanisms of information transfer from extracellular regulators to intracellular effector systems.

The effect of bendamine on the intensity of lipid peroxidation and the activity of the antioxidant defense system of blood in rats in experimental doxorubicin-induced cardiomyopathy

Experimental studies obtained in recent years indicate the urgency of developing drugs of complex action to prevent the development of cardiovascular disease in dogs. This requires a much deeper study of the pathogenesis of heart failure, including cardiomyopathy. The aim of the study was the effect of bendamine on the intensity of lipid peroxidation and the activity of the antioxidant defense system of blood in rats in experimental doxorubicin-induced cardiomyopathy. To reproduce heart failure in rats, an experimental model was used by intraperitoneal administration of doxorubicin at a dose of 2.5 mg/kg 3 times a week for two weeks. The study was performed on white sexually mature young male Wistar rats weighing 180–200 g, which were kept on the standard diet of the institute vivarium of the State Research Control Institute of Veterinary Drugs and Feed Additives. For the study, three groups of rats of 6 animals in each were formed: control group – intact animals; experimental group R1, in which animals were simulated doxorubicin-induced cardiomyopathy by intraperitoneal administration of doxorubicin; experimental group R2, in which animals after injection of doxorubicin, intragastrically administered the drug “Bendamine” at a dose of 20 mg/kg. According to studies, doxorubicin intoxication in rats enhances LPO processes, as indicated by an increased content of lipid hydroperoxides by 47.4 %, diene conjugates – by 21.4 % and TBA-active products – by 24.9 % for animals of the control group. Doxorubicin cardiomyopathy in rats has a decrease in the activity of antioxidant enzymes in the blood of animals. In particular, the activity of catalase decreases by 36.9 % (P ≤ 0.001), and the activity of SOD – by 20.3 % (P ≤ 0.001). In the study of the activity of the glutathione link of the antioxidant defense system, similar changes were found as in the study of the activity of catalase and SOD. The use of the drug “Bendamine” in the rats of the experimental group helped to inhibit the excessive formation of lipid peroxidation products and increase the activity of both enzymatic and non-enzymatic parts of the antioxidant system.

Products of Lipid Peroxidation as a Factor in the Toxic Effect of Silver Nanoparticles.

In our previous study we have shown that nanoparticles have different effects depending on the energy metabolism of the cell, which is an important factor in the context of oncology and diabetes. Here we assess the influence of AgNPs on cellular lipid components in varying glucose concentrations. To assess the effect of silver nanoparticles on cell lipids, we measured cell viability, the fluidity of the cell membranes, the content of amino groups in proteins, the level of lipid peroxidation products, the concentration of 4-hydroxynonenal (4-HNE), and the concentration of lipid peroxides. The obtained results show differences in the formation of lipid peroxidation products in cells exposed to oxidative stress induced by nanoparticles. In addition, we have shown that the metabolic state of the cell is a factor significantly affecting this process.

Exposure of Human Gastric Cells to Oxidized Lipids Stimulates Pathways of Amino Acid Biosynthesis on a Genomic and Metabolomic Level.

The Western diet is characterized by a high consumption of heat-treated fats and oils. During deep-frying processes, vegetable oils are subjected to high temperatures which result in the formation of lipid peroxidation products. Dietary intake of oxidized vegetable oils has been associated with various biological effects, whereas knowledge about the effects of structurally-characterized lipid peroxidation products and their possible absorption into the body is scarce. This study investigates the impact of linoleic acid, one of the most abundant polyunsaturated fatty acids in vegetable oils, and its primary and secondary peroxidation products, 13-HpODE and hexanal, on genomic and metabolomic pathways in human gastric cells (HGT-1) in culture. The genomic and metabolomic approach was preceded by an up-to-six-hour exposure study applying 100 µM of each test compound to the apical compartment in order to quantitate the compounds’ recovery at the basolateral side. Exposure of HGT-1 cells to either 100 µM linoleic acid or 100 µM 13-HpODE resulted in the formation of approximately 1 µM of the corresponding hydroxy fatty acid, 13-HODE, in the basolateral compartment, whereas a mean concentration of 0.20 ± 0.13 µM hexanal was quantitated after an equivalent application of 100 µM hexanal. An integrated genomic and metabolomic pathway analysis revealed an impact of the linoleic acid peroxidation products, 13-HpODE and hexanal, primarily on pathways related to amino acid biosynthesis (p < 0.05), indicating that peroxidation of linoleic acid plays an important role in the regulation of intracellular amino acid biosynthesis.

Cytotoxic Effect of Propolis Nanoparticles on Ehrlich Ascites Carcinoma Bearing Mice

Background and objective Previous studies have demonstrated the anti-cancer effects of propolis. However, its use is limited because of its poor bioavailability. In the present study, the major objective was to improve propolis bioavailability using a nanosuspension formulation. The cytotoxic effect of propolis nanosuspension (PRO-NS) on the Ehrlich ascites carcinoma (EAC) in female Swiss albino mice was investigated in comparison to the free propolis. Materials and methods A propolis-loaded nanosuspension was formulated by applying solvent-antisolvent nano-precipitation technique. The prepared PRO-NS was characterized for average particle size, polydispersity index (PDI) and zeta potential. Also, the morphology of the nanosuspension particles was investigated using scanning electron microscopy (SEM). Moreover, PRO-NS cytotoxicity was tested using EAC bearing mice. The anticancer activity of Pro-NS was assessed by studying tumor volume, life span, viable and non-viable cell count, antioxidant, biochemical estimations and proliferation of EAC cells. Results The results revealed that propolis nanoparticles were relatively spherical in shape with rough surface. The tumor bearing mice treated with PRO-NS showed increased life span and inhibited tumor growth and the proliferation of EAC cells in comparison to the free propolis (p < 0.01). Moreover, Pro-NS ameliorated the increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, IgM and the level of creatinine and urea after implantation of EAC cells. In addition, PRO-NS improved the SOD activity and glutathione content of liver and EAC cells. Furthermore, PRO-NS inhibited the formation of lipid peroxidation products (MDA) and total IgG in EAC tumor bearing mice. Conclusions Our results indicate that PRO-NS has a strong inhibitory activity against growth of tumors in comparison to free propolis. The anti-tumor mechanism may be mediated by preventing oxidative damage, immune-stimulation and induction of apoptosis.

COMPARATIVE STUDY OF BUTANOLIC AND ETHANOLIC EXTRACTS OF TRIBULUS TERRESTRIS FRUITS IN 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-INDUCED HEPATOTOXICITY IN RATS

Objective: To compare hepatoprotective activity of ethanol and butanol fraction of Tribulus terrestris fruits against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hepatic damage in albino rats.Methods: The degree of liver protection was assessed in terms of biochemical parameters, liver marker enzymes, and lipid peroxidation (LPO) in drug-treated and TCDD-intoxicated rats.Results: The results revealed that the elevated serum marker enzymes and biochemical parameters in TCDD-treated rats were significantly reduced toward normal levels in saponin rich fraction of T. terrestris drug-treated animals when comparable to ethanolic extract of T. terrestris drug-treated group. The plant extracts have got a notable inhibitory activity on the formation of LPO products in the basal as well as in the presence of inducers.Conclusion: The plant extracts hindered oxidative damage that occurred to the hepatocytes during TCDD toxicity may be responsible for the hepatoprotective activity in the present study.

Alteration of paraoxonase, arylesterase and lactonase activities in people around fluoride endemic area of Tamil Nadu, India

BackgroundToxicity due to excess fluoride concentration in drinking water is of great concern in people who rely only on the ground water as their water source in many region of the world. MethodsWe collected samples and examined the toxicity of fluoride in a population residing at Salem, Dharmapuri and Krishnagiri districts of Tamil Nadu, India and measured HDL bound enzyme (PON1), erythrocyte membrane bound enzymes (acetylcholinesterase, AChE) and adenosine 5′ triphosphatase (ATPases), plasma enzyme (butyrylcholinesterase, BChE) and rate limiting enzyme in heme biosynthesis (delta aminolevulinic acid dehydratase, δ-ALAD) activities. ResultsIn fluorosis patients, formation of lipid peroxidation product was more in erythrocytes than in plasma. The observation further revealed that there was 50% reduction in the activity of HDL bound anti atherogenic enzyme-paraoxonase (PON1). The activities of membrane bound and signaling enzymes (acetylcholinesterase - AChE and adenosine 5′ triphosphatase - ATPase) of erythrocyte were also diminished. These results suggested that there was defectiveness in the signaling and energy metabolism in fluorosis patients. Altered isoenzyme pattern of lactate dehydrogenase (LDH) in fluorosis samples was observed. Furthermore, the result suggested that both the heart (LDH 1) and liver (LDH 5) were most affected by fluoride toxicity. The study also provided reference values for tests which are used to predict the severity of fluoride toxicity. ConclusionThe toxic effect of fluoride was due to the collective effects on vital protective system rather than single factor.

Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in A/J Min/+ mice.

The International Agency for Research on Cancer has classified red meat as “probably carcinogenic to humans” (Group 2A). In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight) and 60% powder diet) on Apc-driven intestinal carcinogenesis, from week 3–13 of age. Muscle food diets did not differentially affect carcinogenesis in the colon (flat ACF and tumors). In the small intestine, salmon intake resulted in a lower tumor size and load than did meat from terrestrial animals (beef, pork or chicken), while no differences were observed between the effects of white meat (chicken) and red meat (pork and beef). Additional results indicated that intestinal carcinogenesis was not related to dietary n-6 polyunsaturated fatty acids, intestinal formation of lipid peroxidation products (thiobarbituric acid reactive substances, TBARS), or cytotoxic effects of fecal water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to be relatively low in this study. The greatest tumor load was induced by the reference diet RM1, underlining the importance of the basic diets in experimental CRC. The present study in A/J Min/+ mice does not support the hypothesis of a role of red meat in intestinal carcinogenesis.

Biochemical and haematological changes in peripheral blood of rats exposed to chlorpyrifos: protective effect of vitamins A and E combination

Chlorpyrifos is a highly toxic organophosphate compound. It is still among the most widely used insecticide, and the main mechanism of its toxicity is associated with inhibition of cholinesterases. A long with the anticholinesterase action, CPF may affect other biochemical mechanisms, particularly through disrupting pro- and antioxidant balance and inducing free-radical oxidative stress. We studied the action of A and E vitamins on the basic haematological and biochemical parameters of rat peripheral blood after 12 hours of a single chlorpyrifos intoxication. Exposure to 70 mg/kg chlorpyrifos caused a decrease in the total number of red blood cells (RBCs), platelets, and total haemoglobin content. We also observed a decrease in the acid haemolysis resistance of RBCs in peripheral blood of CPF-poisoned rats. Combined exposure to chlorpyrifos and vitamins A and E caused changes in haemolysis resistance of RBCs, approaching the control values. In addition, it was found that chlorpyrifos intoxication disrupt prooxidant-antioxidant balance as evidenced by the increase of lipid peroxidation products: lipid hydroperoxides and thiobarbituric acid reactive substances. However, administration of vitamins A and E during intoxication provided levelling effect on the formation of lipid peroxidation products. CPF intoxication caused an increase of the catalase activity, while superoxide dismutase, glutathione peroxidase and glutathione reductase activities and the content of reduced glutathione decreased. It was revealed that combination of vitamins A and E cause corrective effect at the platelets quantity, and lipid hydroperoxides thiobarbituric acid reactive substances amount of rat peripheral blood.

Ocimum gratissimum is effective in prevention against liver fibrosis in vivo and in vitro.

Ocimum gratissimum is a traditional herb commonly found in tropical regions, which prevents free radical damage and protects the liver from oxidative stress. In this study, we tested in vivo and in vitro the effectiveness of O. gratissimum extracts (OGEs) in anti-hepatic fibrosis in rats. Male Wistar rats were administered with carbon tetrachloride (CCl4) by intraperitoneal injection and varying amounts of oral injection of OGE doses (0-40 mg/kg body weight) for 8 weeks. Our experiments showed that OGE significantly reduced liver damage, including steatosis and fibrosis, in a dose-dependent manner, as well as significantly decreased the elevation in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the formation of lipid peroxidative products during CCl4 treatment. Moreover, OGE-inhibited CCl4-induced liver collagen accumulation and promoted the expression of catalase, an anti-oxidative enzyme. The inhibition of fibrosis factors α-SMA expression was also observed. In primary cultures, OGE significantly inhibited the serum-induced activation of hepatic stellate cells (HSCs), and the expression of α-SMA and collagen α (I). These data suggest that O. gratissimum possesses anti-hepatic fibrosis properties via its anti-oxidative components.

Photohemolysis Sensitized by the Furocoumarin Derivative Alloimperatorin and its Hydroperoxide Photooxidation Product

The dark and photosensitized effects of alloimperatorin methyl ether 1 (hereafter simply alloimperatorin) and its photooxygenation product alloimperatorin hydroperoxide 2 were investigated on human erythrocytes. The results reveal that the furocoumarin 1 photosensitizes efficiently the hemolysis of erythrocytes. The rate of photohemolysis increases on raising the temperature of the postirradiated incubation from 4°C to 37°C. Thermal activation of the photohemolysis and inhibition by 2,6-di-tert-butyl-p-cresol (BHT) suggest that the furocoumarin 1 photosensitizes lipid peroxidation, increasing permeability in the erythrocyte membrane. The hydroperoxide 2 induces dark and photosensitized hemolysis more efficiently than the furocoumarin 1. The rate of hemolysis induced by 2 increases with the incubation temperature and decreases in the presence of tert-butanol and BHT. The hydroperoxide 2 photosensitizes the formation of lipid peroxidation products as shown by the reaction with thiobarbituric acid. This process is diminished by BHT. Our data imply that the photohemolysis sensitized by the furocoumarin 1 is caused by the in situ-formed photooxygenation product 2. Such hydroperoxides are potent hemolytic agents in the dark and especially on photosensitization.

The link between intraneuronal N-truncated amyloid-β peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism

BackgroundAutism is a neurodevelopmental disorder of unknown etiopathogenesis associated with structural and functional abnormalities of neurons and increased formation of reactive oxygen species. Our previous study revealed enhanced accumulation of amino-terminally truncated amyloid-β (Aβ) in brain neurons and glia in children and adults with autism. Verification of the hypothesis that intraneuronal Aβ may cause oxidative stress was the aim of this study.ResultsThe relationships between neuronal Aβ and oxidative stress markers—4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)—were examined in the frontal cortex from individuals aged 7–32 years with idiopathic autism or with chromosome 15q11.2-q13 duplications (dup(15)) with autism, and age-matched controls. Quantification of confocal microscopy images revealed significantly higher levels of neuronal N-truncated Aβ and HNE and MDA in idiopathic autism and dup(15)/autism than in controls. Lipid peroxidation products were detected in all mitochondria and lipofuscin deposits, in numerous autophagic vacuoles and lysosomes, and in less than 5% of synapses. Neuronal Aβ was co-localized with HNE and MDA, and increased Aβ levels correlated with higher levels of HNE and MDA.ConclusionsThe results suggest a self-enhancing pathological process in autism that is initiated by intraneuronal deposition of N-truncated Aβ in childhood. The cascade of events includes altered APP metabolism and abnormal intracellular accumulation of N-terminally truncated Aβ which is a source of reactive oxygen species, which in turn increase the formation of lipid peroxidation products. The latter enhance Aβ deposition and sustain the cascade of changes contributing to metabolic and functional impairments of neurons in autism of an unknown etiology and caused by chromosome 15q11.2-q13 duplication.