Administration Of Lipoic Acid Research Articles

Effect of Modified Diets Pancreatic Oxidative Markers in Streptozotocin-Induced Diabetic Wistar rats Following the Administration of Alpha Lipoic Acid

Despite the availability of various anti-diabetic drugs, diabetes mellitus (DM) remains one of the world’s most prevalent chronic diseases leading to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. This study aimed to investigate the ameliorative effect of modified diets on pancreatic oxidative markers in streptozotocin-induced diabetic Wistar rats following the administration of Alpha lipoic acid, using standard appropriate techniques. Result established that High protein diet (HPD), and with combined administration with alpha lipoic acid in this research resulted in an increased pancreatic superoxide dismutase (SOD) and catalase (CAT) and glutathione (GSH) levels respectively while decreasing pancreatic malondialdehyde (MDA) levels, hence is affirmed as a beneficial strategy in the management of oxidative stress in diabetes. The present study concludes that high protein diets alone and in combination with ALA decreases pancreatic oxidative stress damage caused by streptozotocin toxicity, hence, has the potential to manage diabetes by reducing Reactice oxygen species (ROS) mediated oxidative stress.

Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients

Objective To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. Methods This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. Results ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. Conclusion ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Lipoic acid inhibits cognitive impairment induced by multiple cell phones in young male rats: role of Sirt1 and Atg7 pathway

The utilization of digital technology has grown rapidly in the past three decades. With this rapid increase, cell phones emit electromagnetic radiation; that is why electromagnetic field (EMF) has become a substantial new pollution source in modern civilization, mainly having adverse effects on the brain. While such a topic attracted many researchers’ scopes, there are still minimal discoveries made regarding chronic exposure to EMF. The extensive use of cell phones may affect children's cognition even indirectly if parents and guardians used their phones repeatedly near them. This study aims to investigate possible lipoic acid (LA) effects on cognitive functions and hippocampal structure in young male rats exposed to electromagnetic fields (EMF) emitted from multiple cell phones. Forty young male Wistar rats were randomly allocated into three groups: control, multiple cell phones-exposed and lipoic acid-treated rats. By the end of the experimental period, the Morris water maze was used as a cognitive test. The rats were sacrificed for the collection of serum and hippocampal tissue. These serum samples were then utilized for assessment of Liver function tests. The level ofglutamate, acetylcholine (Ach) and malondialdehyde (MDA) was estimated, in addition to evaluating the expression of autophagy-related protein-7 (Atg7) and Sirt1 genes. The left hippocampal specimens were used for histopathological studies. Results showed that multiple cell phone-exposed rats exhibited shorter latency time to reach the platform by the fifth day of training; additionally, there was a reduction in consolidation of spatial long-term memory. Correspondingly, there was an elevation of hippocampal Ach, glutamate, and MDA levels; accompanied by up-regulation of hippocampal Sirt1 and Atg7 gene expression. Compared to the EMF-exposed group, LA administration improved both learning and memory, this was proved by the significant decline in hippocampal MDA and Ach levels, the higher hippocampal glutamate, the downregulated hippocampal Sirt1 gene expression and the upregulated Atg7 gene expression. In conclusion, EMF exposure could enhance learning ability; however, it interfered with long-term memory consolidation shown by higher hippocampal Ach levels. Lipoic acid treatment improved both learning and memory by enhancing autophagy and hippocampal glutamate level and by the reduced Ach levels and Sirt1 gene expression.

The combined effects of lipoic acid and sodium acetate on metabolism, redox balance, and utilization of yolk reserves of Artemia sp. nauplii

Lipoic acid (LA) has been an antioxidant with proven benefits in different species of productive interest. However, there is evidence of the effect of LA as a growth repressor and, consequently, of zootechnical performance. This study evaluated the effect of the co-administration of LA and short-chain fatty acid, sodium acetate (SA), as an additional source of energy on the utilization of yolk nutrients in Artemia sp. nauplii. A factorial experiment was designed with four levels of LA (0.0, 0.05, 0.5, and 5.0 μM) and four levels of SA (0.0, 2.0, 4.0, and 8.0 mM). Over 24 h, with sampling every 6 h, the total ammoniacal nitrogen (TAN) concentration in water, the concentration of protein, triglycerides, glucose, and the antioxidant capacity (ACAP) was evaluated in the artemia. The electron transporter system (ETS) activity and production of reactive oxygen species (ROS) in vivo were also recorded. Both LA and SA decreased TAN production. At 18 h, LA caused significant decreases in glucose content at the concentrations of 0.5 and 5.0 μM. On the other hand, SA preserved protein values in a dose-dependent manner at 12 h. Regarding ACAP, the LA showed ambivalent effects on this parameter, promoting a higher ACAP at 6 h; however, it promoted a more pro-oxidant state in the metanauplii at 24 h. While the ETS activity increased at 6 h, as an effect of the SA and LA administered separately, the co-administration of LA and SA revealed a possible antagonism that caused a decrease in the ETS activity by the action of LA. As for ROS, a decrease in production rates was found with the administration of LA, which was more noticeable at LA concentrations within the 0 and 2 mM levels of SA from 18 h onwards. Finally, the final energy content showed a scenario of the preservation of the energy reserves of artemia nauplii with the addition of SA. As expected, the LA negatively affected the energy content of the animals; however, the treatment with the highest energy content was the one that received 0.05 μM LA and 8.0 mM SA, suggesting the possibility of using these compounds together in order to compensate the side-effects of LA.

Does Oxidative Stress Along with Dysbiosis Participate in the Pathogenesis of Asthma in the Obese?

The most important environmental factor that can play a key role in the development of asthma in the obese is overproduction of reactive oxygen species (ROS). The aim of the study was to examine changes in the concentration of oxidative stress parameters in the lungs, bronchoalveolar lavage (BAL) fluid and blood of mice in models of asthma or/and obesity caused by high-fat diet (HFD). The concentrations of 4-HNE and isoprostanes in the lungs of the animals were measured. BAL fluid levels of hydrogen peroxide were marked. Additionally, thiobarbituric acid reactive substances (TBARS) and ferric reducing ability of plasma (FRAP) were used as biomarkers of oxidative stress in the blood. Administration of lipoic acid (LA), a probiotic with standard-fat diet (SFD, 10% fat) and low-fat diet (LFD, 5% fat) significantly decreased the concentration of 4-HNE as compared to the OVA (ovalbumin) + HFD group (p < 0.05). Treatment with low-fat diet or LFD in combination with apocynin insignificantly decreased H2O2 values as compared to the OVA + HFD group. Supplementation of probiotic with SFD and LFD significantly decreased the concentration of TBARS as compared to the OVA + SFD and saline + HDF groups (p < 0.05). Significantly lower concentrations of TBARS were also observed in the LA plus LFD group (p < 0.05) as compared to the OVA + HFD group. Low-fat diet with probiotic significantly increased the concentration of FRAP as compared to the obese mice (p = 0.017). Treatment with LFD in combination with LA significantly increased FRAP values as compared to the obese and obese asthmatic mice (p < 0.001).

Patient-derived Enterococcus faecium with inflammatory genotypes promote colitis.

Dysbiosis of gut microbiota promotes colitis in ulcerative colitis (UC). Enterococcus faecium is an important constituent of dysbiotic microbiota. However, the mechanisms underlying E. faecium-induced colitis remain unclear. Overall, 23 E. faecium strains isolated from human feces and 3 commercial strains were inoculated into Il10-/- mice. Mouse colons were histologically evaluated and analyzed using real-time PCR analysis of cytokines. Genes in 26 E. faecium strains were identified by whole-genome shotgun sequencing of genomic DNA. The production of reactive oxygen species (ROS) from each strain was measured. An antioxidant, lipoic acid, was orally administered to the colitis mouse model. Inoculation of E. faecium derived from patients with UC resulted in colitis in Il10-/- mice. The genotypes of 26 strains were characterized by identifying 1893 known genes; clustering all the strains based on the genotypes showed two major groups-inflammatory and probiotic clusters. Additionally, linear discriminant analysis clarified that lipoic acid metabolism was a significantly abundant pathway in the probiotic cluster compared to the inflammatory cluster. Further, the production of ROS was greater in inflammatory than in probiotic strains. Administration of lipoic acid in E. faecium-inoculated mice ameliorated colitis. Enterococcus faecium strains in the inflammatory cluster promoted colitis with higher production of ROS than the strains in the probiotic cluster.

Familial diabetes predisposes PCOS patients to insulin resistance (IR), reproductive impairment and hepatic dysfunction: effects of d-chiro inositol (DCI) and alpha lipoic acid (ALA) administration on hepatic insulin extraction (HIE) index

Objective PCOS is a syndrome is characterized by 2 out of 3 of the criteria established during the Rotterdam Consensus Conference. Recently the issue of insulin resistance (IR) has caught attention. Subjects A group of overweight/obese PCOS patients (n = 30) have been evaluated before and after 3 months of daily integrative administration of d-chiro inositol (DCI) (500 mg) and alpha lipoic acid (ALA) (300 mg). Methods Hormonal and metabolic profiles, oral glucose tolerance test (OGTT) for glucose, insulin and C-peptide response were performed in baseline conditions and after DCI plus ALA treatment. Hepatic Insulin Extraction (HIE) index was computed along the OGTT to evaluate the liver ability in degrading insulin. Results The treatment decreased LH, Androstenedione (A), insulin plasma levels, BMI, HOMA index, AST and ALT. Considering patients for the presence (n = 17) or absence of familial diabetes (n = 13), the greatest improvements occurred in the former patients. Insulin response to OGTT was greatly reduced after the treatment interval in PCOS with familial diabetes. HIE computation disclosed that in presence of familial diabetes liver degradation of insulin is reduced thus leaving a higher amount of circulating insulin. DCI plus ALA administration decreased AST and ALT and restored hepatic insulin clearance since HIE profile was improved. Conclusion Our study demonstrates that in overweight/obese PCOS the predisposition to familial diabetes triggers IR not only through the endogenous impaired DCI and ALA synthesis but also through a reduced hepatic clearance of insulin. DCI plus ALA administration positively improved hormonal, metabolic profiles as well as liver function.

Physiological strength of lipoic acid in copper intoxication

IntroductionThe average concentration of copper in the air, e.g. in the USA it ranges from 5–20 ng/m3, in soil from 5–70 mg/kg, and the intake of copper from food is 1.0–1.3 mg/days for adults (0.014–0.019 mg/kg/day) (Barceloux, 1999). The effect of lipoic acid is reflected in the intensification of ATP synthesis, participates in the assimilation of lactic acid, activates the enzyme cycle of tricarboxylic acid, stimulates the growth of lactic acid bacteria by replacing acetate (acetate transfer factor), stimulates CoA synthesis (fatty acid utilization), prevents liver damage by various toxins, normalizes aldolase and transferase levels.ObjectivesThe aim of this study is to show the useful role of a supplement, lipoic acid, as an antioxidant in the prevention of oxidative stress.MethodsAll procedures were performed after anesthesia of albino rats with ketal in accordance with the principles of sacrifice in laboratories. After medial laparotomy albino rates Wistar soy, a 10% homogenate of brain tissue was made in an appropriate medium and an analysis of acid and alkaline DNase activity was performed (Kocić i sar., 2004).ResultsDNases are thought to be the main executors of apoptosis, responsible for internucleosomal DNA fragmentation, which is the breakdown of chromosomal DNA into oligonucleosome-sized fragments. Administration of lipoic acid has been shown to protect against oxidative stress caused by copper.ConclusionsBased on the results of this research, it can be concluded that lipoic acid is a powerful and powerful antioxidant.DisclosureNo significant relationships.

Role of lipoic acid in multiple sclerosis.

Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with multiple sclerosis (MS). This systematic review aimed to provide a comprehensive overview of both in vitro and in vivo studies describing the pharmacokinetics, efficacy, safety, and mechanism of LA in MS‐related experiments and clinical trials. A total of 516 records were identified by searching five databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane Library. Overall, we included 20 studies reporting LA effects in cell and mouse models of MS and 12 studies reporting LA effects in patients with MS. Briefly, cell experiments revealed that LA protected neurons by inhibiting the expression of inflammatory mediators and activities of immune cells. Experimental autoimmune encephalomyelitis mouse experiments demonstrated that LA consistently reduced the number of infiltrating immune cells in the central nervous system and decreased the clinical disability scores. Patients with MS showed relatively stable Expanded Disability Status Scale scores and better walking performance with few adverse events after the oral administration of LA. Notably, heterogeneity of this evidence existed among modeling methods, LA usage, MS stage, and trial duration. In conclusion, this review provides evidence for the anti‐inflammatory and antioxidative effects of LA in both in vitro and in vivo experiments; therefore, patients with MS may benefit from LA administration. Whether LA can be a routine supplementary therapy warrants further study.

Lipoic acid (LA) dose-dependently protects bone losses in the mandible of rats during the development of osteopenia by inhibiting oxidative stress and promoting bone formation

Our study was carried out to evaluate the effect of lipoic acid (LA) on the densitometric properties, structure and mechanical strength of the mandible of Wistar rats with developing osteopenia. The study used 42 sham-operated (SHO) and ovariectomized (OVX) rats. The OVX rats were randomly divided (n = 6) onto two controls treated subcutaneously with physiological saline (OVX-PhS) and 17β-estradiol (OVX-E2), respectively, and onto four experimental OVX groups that received LA in the doses of 12.5, 25, 50 and 100 mg/kg/day for 28 days. The results demonstrated that the lack of estrogen brought about osteopenic bone changes, especially in the trabecular compartment. In addition, while the usage of LA in the doses of 12.5 and 25 LA had no effect in OVX rats, the dose of 100 effectively inhibited osteopenic changes of the mandible. This dose maintained structural, densitometric and mechanical parameters at levels like that in the SHO and OVX-E2 groups by inhibiting the destructive influence of oxidative stress. Dose 50, however, was revealed to be the most effective. It not only inhibited atrophic changes and the influence of oxidative stress, but also stimulated the formation of mandibular bone tissue. Our results suggest that the administration of LA is effective in preventing atrophic changes in the mandibular bone tissue in conditions of ovarian hormone deficiency and suggest its potential in the therapy of osteoporosis.

Effects of lipoic acid supplementation on age- and iron-induced memory impairment, mitochondrial DNA damage and antioxidant responses.

To investigate the effects of lipoic acid (LA) supplementation during adulthood combined with supplementation later in life or LA administration only at old age on age-induced cognitive dysfunction, mitochondrial DNA deletions, caspase 3 and antioxidant response enzymes expression in iron-treated rats. Male rats were submitted to iron treatment (30mg/kgbody wt of Carbonyl iron) from 12 to 14th post-natal days. Iron-treated rats received LA supplementation (50mg/kg, daily) in adulthood and old age or at old age only for 21days. Memory, mitochondrial DNA (mtDNA) complex I deletions, caspase 3 mRNA expression and antioxidant response enzymes mRNA expression were analyzed in the hippocampus. LA administration in adulthood combined with treatment later in life was able to reverse age-induced effects on object recognition and inhibitory avoidance memory, as well as on mtDNA deletions, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, and antioxidant enzymes disruption induced by iron in aged rats. LA treatment only at old age reversed iron-induced effects to a lesser extent when compared to the combined treatment. The present findings support the view that LA supplementation may be considered as an adjuvant against mitochondrial damage and cognitive decline related to aging and neurodegenerative disorders.

Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase activity? A contribution to the ongoing discussion.

The aim of the study presented here was an attempt to answer the question posed in the title: Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase (ALDH) activity? Here, we investigated the effect of administration (separately or jointly) of lipoic acid (LA), nitroglycerin (GTN), and disulfiram (DSF; an irreversible in vivo inhibitor of all ALDH isozymes (including ALDH2)), on the development of tolerance to GTN. We also assessed the total activity of ALDH in the rat liver homogenates. Our data revealed that not only DSF and GTN inhibited the total ALDH activity in the rat liver, but LA also proved to be an inhibitor of this enzyme. At the same time, the obtained results demonstrated that the GTN tolerance did not develop in GTN, DSF and LA jointly treated rats, but did develop in GTN and DSF jointly treated rats. This means that the ability of LA to prevent GTN tolerance is not associated with the total ALDH activity in the rat liver. In this context, the fact that animals jointly receiving GTN and DSF developed tolerance to GTN, and in animals that in addition to GTN and DSF also received LA such tolerance did not develop, is - in our opinion - a sufficient premise to conclude that the nitrate tolerance certainly is not caused by a decrease in the activity of any of the ALDH isoenzymes present in the rat liver, including ALDH2. However, many questions still await an answer, including the basic one: What is the mechanism of tolerance to nitroglycerin?

Can Lipoic Acid Attenuate Cardiovascular Disturbances Induced by Ethanol and Disulfiram Administration Separately or Jointly in Rats?

The exogenous lipoic acid (LA) is successfully used as a drug in the treatment of many diseases. It is assumed that after administration, LA is transported to the intracellular compartments and reduced to dihydrolipoic acid (DHLA) which is catalyzed by NAD(P)H-dependent enzymes. The purpose of this study was to investigate whether LA can attenuate cardiovascular disturbances induced by ethanol (EtOH) and disulfiram (DSF) administration separately or jointly in rats. For this purpose, we measured systolic and diastolic blood pressure, recorded electrocardiogram (ECG), and estimated mortality of rats. We also studied the activity of aldehyde dehydrogenase (ALDH) in the rat liver. It was shown for the first time that LA partially attenuated the cardiac arrhythmia (extrasystoles and atrioventricular blocks) induced by EtOH and reduced the EtOH-induced mortality of animals, which suggests that LA may have a potential for use in cardiac disturbance in conditions of acute EtOH intoxication. The administration of EtOH, LA, and DSF separately or jointly affected the ALDH activity in the rat liver since a significant decrease in the activity of the enzyme was observed in all treatment groups. The results indicating that LA is an inhibitor of ALDH activity are very surprising.

Histological Comparative Study between the Possible Effect of Stem Cells and α- Lipoic Acid on Rat Testes Treated by Cyclophosphamide

Background and Objectives: Testicular dysfunction is the most common side effect of chemotherapeutics as cyclophosphamide (CP). Stem cells (SCs) transplantation has become a new therapeutic strategy in the treatment of male infertility. Lipoic acid (LA) is one of the effective antioxidants. This work aimed to evaluate the histological changes induced by CP on the rat testes and the possible ameliorating role of SCs and LA.Methods and Results: 37 male albino rats were divided into: group A (Control), group B (experimental) that received intra peritoneal (IP) injection of 15 ml/kg CP for 6 wks. Then, they were subdivided into 5 subgroups: B1 (model) continued receiving CP for 11 wks, B2 (SCs) injected IP with single dose of SCs (1x106 per animal), B3 (LA) injected IP with both CP and LA (10 mg ⁄ kg ⁄ every other day) for 11 wks, B4 (SCs + LA) treated with both SCs and LA and B5 (recovery) left without any treatment for 11 wks. Histological, immunohistochemical and morphometric studies were performed. B1 and B5, revealed the toxic effect of CP; such as atrophy, degeneration, incomplete spermatogenic series in most seminiferous tubules. Spermatogenic and Leydig cells showed negative immunoreaction with BCl2. These changes were ameliorated in B2, B3andB4.These ameliorations were better in B4 than in B2andB3.Conclusions: CP can induce testicular lesions in rats. Withdrawal of CP does not ameliorate these effects. The concomitant administration of SCs and LA with CP improved these lesions. Meanwhile combined treatment with SCs + LA resulted in better improvement more than using each one of them singly.

The influence of apocynin, lipoic acid and probiotics on antioxidant enzyme levels in the pulmonary tissues of obese asthmatic mice

Bronchial asthma and obesity are common health problems. Obesity is already responsible for 300,000 deaths per year. AimsThe aim of the present study was to assess whether apocynin, alpha lipoic acid and probiotic administration in combination with low-fat diet supplementation influences the levels of antioxidant enzymes in the pulmonary tissues of obese asthmatic mice. Main methodsThe study was performed on male C57/BL6 mice divided into 10 groups: (I) control; (II) asthma; (III) obesity; (IV) asthma + obesity; (V) asthma + obesity + apocynin p.o. 15 mg/kg/day for 12 weeks; (VI) asthma + obesity + low-fat diet for 12 weeks; (VII) asthma + obesity + low-fat diet for 12 weeks with apocynin p.o. 15 mg/kg/day; (VIII) asthma + obesity + low-fat diet with probiotics for 12 weeks; (IX) asthma + obesity + low-fat diet for 12 weeks with lipoic acid p.o. 100 mg/kg/day for 12 weeks; (X) asthma + obesity + standard diet with probiotics for 12 weeks. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity were examined. The administration of apocynin alone and apocynin in combination with a low-fat diet resulted in a significant increase in SOD values (respectively p < 0.001; p = 0.010). Application of probiotics resulted in a decrease in CAT activity (p = 0.037) and an increase in GPx activity (p < 0.001) compared to obese asthmatic mice. The administration of lipoic acid resulted in an increase in GR activity (p = 0.024 vs. control). Key findingsSupplementation containing apocynin, lipoic acid and probiotics has a positive influence on the antioxidant capacity of the pulmonary tissues of obese asthmatic mice. SignificanceThese results may contribute to the development of new therapeutic approaches.

Role of alpha lipoic acid on cyclophosphamide induced cardiotoxicity in adult male albino rat: histological study

Background: Cyclophosphamide is a chemotherapeutic agent used for treatment of leukemia, lymphoma and myeloma. Several studies reported wide range of cyclophosphamide induced cardiotoxicity in cancerous patients. Alpha lipoic acid is a natural antioxidant used widely for prevention and treatment of different conditions. Aim of the work: This work was conducted to study the role of alpha lipoic acid in cyclophosphamide induced cardiotoxicity basing on histological and ultrastructural studies. Material and Methods: Forty-four adult male Albino rats were divided into four groups: group I (control), group II (alpha lipoic acid -treated) in a dose (25 mg/kg body weight/day) given orally, group III (cyclophosphamide -treated) in a dose (200 mg/kg body weight) single dose injected intraperitoneally and group IV (alpha lipoic acid plus cyclophosphamid-treated). The experiment was conducted for ten days. Cardiac muscle specimens were subjected to light, electron microscopic and immunohistochemical study. Results: Microscopic examination of cardiac muscle of cyclophosphamide treated group (III) showed focal disruption and vacuolation of cardiac muscle fibers with mononuclear infiltration between cardiac muscle fibers. Ultrastructurally, destruction of myofibrils, swollen, irregular arranged mitochondria and dilated SER were noted. Some nuclei showed chromatolysis and others were heterochromatic with irregular nuclear membrane. These results were confirmed by significant decrease in Bcl2. The intercellular spaces were wide contained dilated congested blood vessels and collagen. Alpha lipoic acid administration improved cardiac muscle architecture but still not attained the complete normal morphology Conclusion: Supplementation of alpha lipoic acid in concomitant with cyclophosphamide (CYP) can ameliorate the CYP induced cardiac injury.

MITOCHONDRIAL DISEASES (Posters): P.183MELAS and reversible cerebral vasoconstriction

A 22-year-old woman was admitted due to fever and severe headache for 10 days and altered mental status and generalized tonic-clonic seizures for 8 days. She had a short stature and hairy body surface, and her mother passed away about ten years ago due to ``encephalitis''. Laboratory data showed elevated lactate in both peripheral blood and CSF. Brain MRI using diffusion weighted imaging revealed hyperintense lesions located in the whole right temporal and occipital lobes and pulvinar of thalamus. MR angiography revealed segmental stenoses at the right P1 and M2-3 junction. Muscle biopsy showed typical RRF and SSV. A genetic study revealed a mitochondrial DNA A3243G point mutation. The patient's clinical symptoms and MRI/MR angiography (MRA) findings improved after the administration of L-arginine, L-carnitine, lipoic acid, vitamin B and dexamethasone. Therefore we speculate the possible pathophysiology just like RCVS (reversible cerebaral vasoconstriction syndrome) involving in the stroke-like episodes of MELAS.

Activity of serum paraoxonase 1, lipid profile and atherogenic indexes in diabetic induced rats treated with alpha lipoic acid

Background: Paraoxonase 1 (PON1) is an enzyme attached to high density lipoprotein (HDL-C) which has antioxidant and anti-atherogenic activities. Objectives: In this study, we investigated the effects of alpha lipoic acid on PON1 activity, lipid profile and atherogenic index as well as correlation between PON1 activities and HDL-C in diabetic rats. Materials and Methods: Thirty adult male rats were distributed in three experimental groups in this study. Control (group I), diabetic (group II) and diabetic animals treated with alpha lipoic acid (group III) group. Diabetes mellitus was induced in rats in groups II and III by a single dose of alloxan monohydrate (100 mg/kg; subcutaneous) and then treatment was performed with administration of alpha lipoic acid (100 mg/kg intraperitoneally) in group III for 6 weeks. Blood samples were collected from animals to measure the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C), HDL-C, PON1 activity and correlation the between HDL-C and atherogenic index by PON1. Results: Statistical analysis showed that alpha lipoic acid significantly (P<0.05) inhibited the increase of TG, TC, LDL-C, VLDL, atherogenic index, atherogenic coefficient (AC), and cardiac risk ratio (CRR) when compared to diabetic rats in group II. HDL-C level was increased by alpha lipoic acid. The activity of PON1 was significantly (P<0.05) decreased in diabetic rats and treatment with alpha lipoic acid increased the PON1 activity. Moreover, the activity of PON1 correlated positively with HDL-C and negatively with AC, CRP 1 and CRP2. Conclusions: This study demonstrated that the administration of alpha lipoic acid can improve PON1 activity, lipid metabolism, atherogenic index and is able to reduce the risk of coronary artery diseases and atherosclerosis in diabetic rats.

Lipoic Acid and Progesterone Alone or in Combination Ameliorate Retinal Degeneration in an Experimental Model of Hereditary Retinal Degeneration.

Retinitis pigmentosa (RP) is a group of inherited retinopathies characterized by photoreceptors death. Our group has shown the positive progesterone (P4) actions on cell death progression in an experimental model of RP. In an effort to enhance the beneficial effects of P4, the aim of this study was to combine P4 treatment with an antioxidant [lipoic acid (LA)] in the rd1 mice. rd1 and control mice were treated with 100 mg/kg body weight of P4, LA, or a combination of both on postnatal day 7 (PN7), 9, and 11, and were sacrificed at PN11. The administration of LA and/or P4 diminishes cell death in rd1 retinas. The effect obtained after the combined administration of LA and P4 is higher than the one obtained with LA or P4 alone. The three treatments decreased GFAP staining, however, in the far peripheral retina, and the two treatments that offered better results were LA and LA plus P4. LA or LA plus P4 increased retinal glutathione (GSH) concentration in the rd1 mice. Although LA and P4 are able to protect photoreceptors from death in rd1 mice retinas, a better effectiveness is achieved when administering LA and P4 at the same time.

The Correlation between Administration of Alpha Lipoic Acid and Malondialdehyde Level on Traumatic Brain Injury Model Rat’s Brain

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive brain trauma that cancontinues to be dementia, alzheimer and parkinsonism. Traumatic brain injury increased free radicals in brain thatcaused oxidative stress and induced lipid peroxidation, neuron damage and producing MDA. The purpose is todetermine the correlation between administration of ALA and MDA level in rat’s brain model of traumatic braininjury and its effective dose. Rats are randomLy divided into 7 groups. Normal group without treatment, K(-) wasgiven NaCl 0,9% 1,5 mL, K(+) was given citicoline 6,75 mg, K1 was given ALA 1,0125 mg, K2 was given ALA 2,025mg, K3 was given ALA 4,05 mg, K4 was given ALA 8,1 mg and received 30 days traumatic brain injury treatment bydropped 245 g load on the rat’s head at 35 cm height. MDA level in brain were measured on the 31th day withMDA-TBA method by spectrofotometer. The averages of MDA levels were N 1,64 μg/mL; K(+) 2,09 μg/mL; K(-) 4,87μg/mL; K1 2,73 μg/mL; K2 2,68 μg/mL; K3 2,20 μg/mL and K4 2,02 μg/mL. Pearson’s analysis shows strong andsignificant negative correlation (r= -0,790) between administration of ALA and MDA level in rat’s brain model oftraumatic brain injury (p&lt;0,05). The effective dose of ALA is 8,625 mg/150gBW.Keywords : Alpha lipoic acid, MDA, traumatic brain injury, CTE