Administration Of Alpha-lipoic Acid Research Articles

Effects of alpha-lipoic acid on spatial learning and memory, oxidative stress, and central cholinergic system in a rat model of vascular dementia

Brain oxidative stress due to chronic cerebral hypoperfusion was considered to be the major risk factor in the pathogenesis of vascular dementia. In this study, we investigated the protective efficacy of alpha-lipoic acid, an antioxidant, against vascular dementia in rats, as well as the potential mechanism. Bilateral common carotid arteries occlusion (BCCAO) induced severe cognitive deficits tested by Morris water maze (MWM), along with oxidative stress and disturbance of central cholinergic system. However, administration of alpha-lipoic acid (50mg/kg, i.p.) for 28 days significantly restored cognitive deficits induced by BCCAO. Biochemical determination revealed that alpha-lipoic acid markedly decreased the production of malondialdehyde (MDA) and the generation of reactive oxidative species (ROS), and increased the level of reduced glutathione (GSH) in the hippocampal tissue. Additionally, alpha-lipoic acid raised the level of acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreased the activity of acetycholinesterase (AChE) in the hippocampus. These results indicated that treatment with alpha-lipoic acid significantly improved behavioral alterations, protected against oxidative stress, and restored central cholinergic system in the rat model of vascular dementia induced by BCCAO.

The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity

Amikacin (AK) is an antibacterial drug, but it has remarkable nephrotoxic and ototoxic side effects due to increase in reactive oxygen radicals. This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on AK-induced nephrotoxicity. Three different groups of rats (n = 6) were administered saline (control), AK (1.2 g/kg, intraperitoneally), ALA (100 mg/kg, p.o.) and AK combination (ALA one day before the AK for five days). Renal function, oxidative stress markers and histological changes were evaluated at the end of the experiment. Malondialdehyde was increased as an indicator of free radical formation in AK-induced group and decreased with ALA treatment. While catalase activity was increased significantly, superoxide dismutase and glutathione peroxidase activities were not statistically significant increased with ALA treatment. The result showed that AK enhanced levels of urea, creatinine and blood urea nitrogen in serum significantly. Administration of ALA reduced these levels of biochemical markers. Histopathological observations were confirmed by biochemical findings. In conclusion, ALA is suggested to be a potential candidate to ameliorate AK-induced nephrotoxicity.

Effect of the Administration of Alpha-Lipoic Acid on Contrast Sensitivity in Patients with Type 1 and Type 2 Diabetes

The aim of this study was to estimate the effects of oral supplementation of alpha-lipoic acid (ALA) on contrast sensitivity (CS) in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The study included 12 patients with T1DM aged 43±12 years, 48 patients with T2DM aged 59±10 years, and 20 control subjects aged 33±8 years. Patients from each studied group, including the control group, were randomly assigned to receive 300 mg of ALA orally once daily for 3 months. CS was evaluated with the Functional Acuity Contrast Test (FACT, Stereo Optical). In the group of patients with T1DM receiving ALA for 3 months CS remained stable and improved in those with T2DM. Reduction of CS in both T1DM and T2DM patients without alpha-lipoic acid supplementation was observed. In the control group on alpha-lipoic acid supplementation, CS improvement was noticed at one spatial frequency. Changes in the CS were observed, despite stable visual acuity and eye fundus image in all studied subjects. Our study demonstrated that oral administration of alpha-lipoic acid had influence on CS in both T1DM and T2DM patients.

Investigation of the Effects of Alpha Lipoic Acid Application on Total Antioxidant and Oxidant Status, Paraoxonase, and Total Sialic Acid Levels in Laminectomized Rabbits

The objective of this study is to investigate the effect of intramuscular administration of alpha-lipoic acid (ALA) on total antioxidant (TAS), total oxidant (TOS), paraoxonase (PON) and total sialic acid (TSA) levels in laminectomized rabbits. In the study, twenty four white New Zeeland rabbits weighing 3-4 kg were used. The investigation was carried out with three experiment and one control group consisting of six animals of each. No intervention has been done to the control group. Animals in the Group I received 50 mg/kg/day IM ALA (Thioctacid 600 T, M, EDA, Hamburg) without undergoing laminectomy. Group II underwent laminectomy; Group III underwent laminectomy and treated with IM ALA. The experiment lasted 45 days and blood samples were taken on 0, 15th, 30th, and 45th days from the animals. TAS, TOS, PON and TSA levels were measured in the serum. We conclude that ALA treatment would be beneficial in laminectomized rabbits in order to suppress inflammatory process and to expedite recovery.

Alpha-lipoic acid inhibits peridural fibrosis following laminectomy through the inactivation of TGF-β1, PDGF, PAI-1 and IL-6 expressions.

The objective of this study was to investigate the antifibrotic effect of parenteral administration of alpha-lipoic acid (ALA), which has been reported to reduce fibrosis in the liver, oral mucosa, and peritoneum, in laminectomized rabbits as a potential candidate for the prevention of peridural fibrosis. Twelve adult New Zealand white male rabbits were divided into control (n=6) and ALA treatment groups (n=6). Laminectomy of the lumbar spine was performed in all animals, and ALA was administered intramuscularly in six rabbits composing the treatment group. Total RNA obtained from the paraffin-embedded tissues was analyzed for transforming growth factor-β1 (TGF-β1), plateletderived growth factor (PDGF), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). mRNA investigations showed that TGF-β1, PDGF, PAI-1 and IL-6 gene expressions, which constitute strong evidence for the development of fibrosis, were significantly lower in the treatment group compared with the results obtained from the control group. According to the histological peridural grading, the ALA-treated group showed significantly less peridural fibrosis than the control group. Intramuscular administration of ALA is a promising treatment for the prevention of peridural fibrosis in the postoperative period.

Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial

Chemotherapy-induced peripheral neuropathy is frequently a dose-limiting factor in cancer treatment and may cause pain and irreversible function loss in cancer survivors. We tested whether alpha-lipoic acid (ALA) could decrease the severity of peripheral neuropathy symptoms in patients undergoing platinum-based chemotherapy. Cancer patients 18 years or older were randomly selected to receive either 600 mg ALA or a placebo three times a day orally for 24 weeks while receiving chemotherapy regimens including cisplatin or oxaliplatin. Neuropathy was measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale and the NCI Common Toxicity Criteria for Adverse Events neurotoxicity grades. Results from timed functional tests and the Brief Pain Inventory (BPI) were secondary endpoints. Seventy of 243 (29 %) patients completed the study (24 weeks). Both the ALA and the placebo arms had a comparable drop-out rate. No statistically significant differences were found between the ALA and the placebo groups for FACT/GOG-Ntx scores, BPI scores, and patients' functional outcomes. This strategy of oral ALA administration was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. High attrition rates due to poor patient compliance and manner of dosage administration in this trial demonstrated a lack of feasibility for this intervention. Future studies to explore ALA as a neuroprotective agent should take heed of the barriers confronted in this study.

The effect of alpha-lipoic acid in ovariectomy and inflammation-mediated osteoporosis on the skeletal status of rat bone

Osteoporosis is a high mortality and morbidity ranged skeletal disease and results in high costs of medical care in the European Union. We evaluated the possible protective effect of alpha-lipoic acid (ALA) on rat bone metabolism in ovariectomy and inflammation-mediated osteoporosis models. Groups were designed as: (1) sham; (2) sham+inflammation; (3) ovariectomy (OVX); (4) ovariectomy+ALA—25mg/kg; (5) ovariectomy+ALA—50mg/kg; (6) ovariectomy+inflammation; (7) ovariectomy+inflammation+ALA—25mg/kg; and (8) ovariectomy+inflammation+ALA—50mg/kg groups. OVX groups were allowed to recover for two months. Then, inflammation was induced in inflammation groups by subcutaneous talc injection. ALA—25mg/kg and 50mg/kg were administered to drug groups chronically. The skeletal response was assessed by bone mineral density (BMD), osteopontin and osteocalcin measurements. Pro-inflammatory cytokine measurements (interleukin (IL)-1beta, interleukin-6, and tumor necrosis factor-alpha) were performed to observe inflammatory process. In OVX, INF and OVX+INF groups, BMD levels were lowest and osteocalcin, osteopontin, IL-1beta, IL-6, and TNF-alpha levels were highest when compared to sham group. ALA administration increased BMD levels and decreased osteocalcin, osteopontin, IL-1beta, IL-6, and TNF-alpha levels versus OVX and OVX+INF control groups. Both in senile and postmenopausal osteoporosis, the balance in coupling were destroyed on behalf of bone resorption. ALA had a protective effect on both senile and postmenopausal osteoporosis. The positive effect of this drug in these osteoporosis models might originate from its positive effects on bone turnover markers and cytokine levels. From this perspective, ALA may be a candidate for radical osteoporosis treatment both in senile and postmenopausal types clinically at the end of advanced studies.

The Anti-neoplastic Effects of Alpha-Lipoic Acid: Clinical Benefits in System Tumors besides Lung Carcinomas

I read with great interest the recent article by Kim et al. [1]. Interestingly, alpha-lipoic acid has recently been shown to exert anti-neoplastic effects in a number of systemic tumors other than lung carcinomas. For instance, alpha-lipoic acid exerts anti-neoplastic effects in colon carcinomas. DHL-HisZnNa is a newer alpha-lipoic acid derivative that has shown similar anti-neoplastic effects in colon cancer cell lines [2]. Levels of retinoblastoma protein are attenuated by DHL-HisZnNa while a simultaneous accentuation of p21 levels is seen. Similarly, anti-proliferative effects have been seen in hepatocellular carcinomas following the administration of alpha-lipoic acid in conjunction with caffeic acid and a new synthesized lipoyl-caffeic conjugate. This combination results in enhanced interleukin 10 levels and attenuated tumor necrosis factor-α levels. Similarly, alpha-lipoic acid derivatives such as CPI-613 demonstrate anti-neoplastic effects in pancreatic malignancies by disrupting the mitochondrial metabolism in tumor cells resulting in accentuated apoptosis in these cells. For instance, Schwartz et al. [3] have recently reported the case of an 80-year-old female with pancreatic adenocarcinoma and hepatic metastases who responded favorably to a treatment regimen in which the efficacy of gemcitabine was enhanced by using a combination of hydroxycitrate in conjunction with alpha-lipoic acid. Hydroxycitrate and alpha-lipoic acid combinations also exert anti-proliferative effects in mouse bladder carcinoma-2 cell line bladder transitional cell carcinoma lines, which is equivalent to the anti-neoplastic effects exerted by conventional chemotherapeutic agents such as 5-fluorouracil [4]. Similarly, alpha-lipoic acid exerts anti-proliferative effects in breast carcinomas. These anti-neoplastic effects are mediated by its attenuating effect on matrix metalloproteinase (MMP)-2 and MMP-9 levels. It not only down-regulates the expression of these molecules but also decreases their activity. In particular, it decreases cellular migration and cellular motility, resulting in decreased metastases. Besides this, it also alters the Bax/Bcl-2 ratio [5]. A simultaneous increase in p27 (kip1) expression is seen, resulting in accentuated apoptosis in breast malignancies. Alpha-lipoic acid also demonstrates benefits in the management of dermatological malignancies. It exerts these effects by inhibiting proliferation and by accentuating apoptosis in these tumors. It also enhances the apoptosis of cells with aberrant nuclei, thus further attenuating tumor growth in these malignancies. These effects have been seen particularly in B16-F10 melanoma cell lines [5]. The above examples clearly illustrate the anti-neoplastic effects of alpha-lipoic acid and the need for further studies to assess its potential efficacy in the management of other systemic tumors.

Ameliorative role of Alpha lipoic acid (ALA) in sodium arsenite (NaAsO2) induced neurotoxicity in developing rat cerebellum

The present study was designed to evaluate the effects of ALA on arsenic (As) induced alterations in developing rat cerebellum. Pregnant Wistar rats, obtained from Experimental Animal Facility (EAF) after ethical clearance from Institutional Ethical Committee of AIIMS were maintained on a 12 hr light‐dark cycle with ad libitum access to food and water. The day of birth of pups was designated as postnatal day (PND) 0. Mother reared pups were divided into control (normal and sham) and experimental groups receiving NaAsO2 alone or along with ALA from PND 1 to 21. Behavioral parameters (tail hung, negative geotaxis and water maze) were carried out on PND 21. Animals were sacrificed on PND 22 and the fresh cerebella were processed for estimation of antioxidant glutathione (GSH) and Lipid peroxidation product malondialdehyde (MDA) levels. Cerebella from perfusion fixed animals were processed for paraffin embedding and Cresyl Violet stained sections were observed for morphological features. Immunohistochemical expression of synaptophysin (Syp) and Myelin basic protein (MBP) was studied in cryocut sections. The observations of present study revealed alteration in cerebellar morphology and behavioral dysfunction in rat pups exposed to NaAsO2.Co‐administration of ALA resulted in partial reversal of As induced decline in the behavioral parameters, decreased GSH levels, elevated MDA levels, disruption of cerebellar cytoarchitecture and decrease in Syp and MBP expression suggesting thereby protective role of ALA in NaAsO2 induced neurotoxicity.DST INSPIRE Fellowship, Govt. of India (110053) to Parul Kaushal is acknowledged.

Does alpha-lipoic acid treatment play a role on oxidative stress and insulin resistance in overweight/obese patients?

With great interest, we read the recent manuscript by Yan et al. [1] regarding the beneficial effects of alpha-lipoic acid (ALA) treatment on oxidative stress and insulin resistance in overweight/obese patients. The authors have performed a double-blinded, randomized, cross-over trial to investigate whether oral ALA administration will lower the risk of cardiovascular disease by decreasing the level of oxidative stress markers including “oxidized LDL” and “8-Iso Prostaglandin F2 alpha” or improving insulin sensitivity analyzing HOMA-IR levels.

Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

BackgroundHyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats.MethodsAnimals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO) rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day) administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry.ResultsWestern blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK) signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA.ConclusionsALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

Alpha-lipoic acid pre- and post-treatments provide protection against in vitro ischemia-reperfusion injury in cerebral endothelial cells via Akt/mTOR signaling

Alpha-lipoic acid (ALA) is an endogenous short-chain fatty acid that has beneficial protective effects against various vascular diseases. In this study, we sought to determine whether ALA could induce pre- or post-treatment protective effects against simulated ischemia and reperfusion-induced cerebral endothelial cell (CEC) injury by activating the Akt/mTOR pathway. CECs are currently considered to be an important target for ischemia therapy. Mouse brain endothelial cells (bEnd.3) and primary cultures of CECs were subjected to 6h of oxygen glucose deprivation (OGD) followed by 4h of simulated reperfusion, either alone or together with ALA administration before (pre-treatment) or immediately after (post-treatment) OGD. We found that pre-treatment administration of ALA reduced the OGD and simulated reperfusion-induced lactate dehydrogenase (LDH) release in bEnd.3 cells in a dose-dependent manner and that 1mM ALA pre- and post-treatments provided protection in both bEnd.3 cells and primary cultures of CECs. However, rapamycin, an mTOR inhibitor, was able to thoroughly abolish the protective effects of ALA. Western blotting showed that the ALA pre- and post-treatments up-regulated the phosphorylation of Akt, mTOR, S6K and 4E-BP1 in both bEnd.3 cells and primary cultures. However, after pre-treatment with rapamycin, the level of Akt phosphorylation was decreased in primary cultures of CECs but could still be restored by ALA, whereas the levels of mTOR, S6K and 4E-BP1 phosphorylation were significantly decreased and could not be restored. These results suggest that ALA pre- and post-treatments provide protective effects against simulated ischemia and reperfusion-induced CEC injury by promoting the Akt/mTOR pathway and that mTOR is required for ALA protection.

Experimental Study of the Neuroprotective Properties of Alpha-Lipoic Acid and Superoxide Dismutase in Cerebral Ischemia in Rats

The aim of the present work was to study the neuroprotective roles of alpha-lipoic acid and superoxide dismutase in focal and total cerebral ischemia in rats. Experiments were performed on Wistar rats (n = 125): 1) to assess neuroprotective effects in conditions of permanent occlusion of the left middle cerebral and left common carotid arteries (n = 26); 2) to study the effects of these agents and their combination on survival in conditions of occlusion of both carotid arteries (n = 81). An infarct-limiting effect was seen in the group in which alpha-lipoic acid was given 30 min before ischemia (p = 0.00004). Administration of superoxide dismutase 30 min before ischemia or alpha-lipoic acid immediately before ischemia did not decrease the size of the necrotic area. Administration of alpha-lipoic acid or the combination of alphalipoic acid and superoxide dismutase led to an increase in the animals’ survival time (p = 0.003, p = 0.013), while use of superoxide dismutase alone produced no increase (p = 0.127). Alpha-lipoic acid induced a neuroprotective effect in focal and total cerebral ischemia. Superoxide dismutase did not have a protective effect in ischemia.

Changes in expression profiles of antioxidant enzymes in diabetic rat kidneys

In diabetes mellitus, increased formation of reactive oxygen species due to high level of glucose in both blood plasma and tissues creates oxidative stress and damages the tissues. Antioxidants together with the antioxidant enzymes are very important in order to protect the cells against oxidative damage. Differential expressions of both mRNA and proteins of major antioxidant enzymes in streptozotocin-induced diabetic rat kidneys were measured with the help of real-time polymerase chain reaction and western blot analysis, respectively. Furthermore, effects of two strong antioxidants α-lipoic acid, vitamin C and their combination on the regulation of both expressions and the activities of antioxidant enzymes were also studied. In diabetic rat kidney tissue, both catalase and glutathione peroxidase activities were reduced (although mRNA expression for both was greatly increased) when compared with controls. No significant change was observed in superoxide dismutase (SOD) activity. Alpha-lipoic acid increased catalase activity towards the control values. Combined administration of alpha-lipoic acid and vitamin C increased the activities of both catalase and SOD, demonstrating a posttranslational effect. Glutathione concentrations were decreased in diabetic kidney; alpha-lipoic acid treatment partially restored the glutathione levels. All data showed the importance of post-transcriptional and translational regulation of the antioxidant enzyme activities against oxidative stress that is associated with diabetes.

α-Lipoic Acid, Diabetic Neuropathy, and Nathan’s Prophecy

Both oral and intravenous administration of alpha-lipoic acid (ALA) has been investigated as add-on treatment for diabetic peripheral neuropathy. The recent Neurological Assessment of Thioctic Acid in Diabetic Neuropathy (NATHAN) 1 trial has shown that 4-year oral ALA administration is of some value in achieving a clinically meaningful improvement and a slight delay in the progression of neuropathic deficits among patients with mild/moderate diabetic peripheral neuropathy. Despite these promising results, important questions remain to be answered, mainly appropriate patient selection and optimal treatment duration. Moreover, a cost-benefit analysis would be useful.

Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study.

Despite well-controlled blood glucose levels, diabetic complications still inevitably take place via several mechanisms including excessive generation of free radicals in patients who suffer from diabetes mellitus (DM). A randomized double-blind placebo-controlled clinical trial to investigate the effectiveness of oral supplementation of DL-alpha-lipoic acid (ALA) on glycemic and oxidative status in DM patients was conducted. Thirty eight outpatients with type 2 DM were recruited and randomly assigned to either placebo or treatment in various doses of ALA (300, 600, 900, and 1200 mg/day) for 6 months. Following the treatment, all subjects were evaluated for glucose status and oxidative biomarkers. Results showed that fasting blood glucose, HbA1c trended to decrease in a dose-dependent manner. Increase of urinary PGF2α-Isoprostanes (F2α-IsoP) was noted in placebo but not ALA-treated groups, indicating possible suppressing action of ALA on lipid peroxidation in DM subjects. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) levels, however, were similar in both placebo and ALA groups as well as urinary microalbumin and serum creatinine. Safety evaluation was monitored and treatment was found to be well tolerated despite some minor side effects. Results from this study reflected the benefits of ALA in glucose status with slight efficiency on oxidative stress-related deterioration in DM patients.

Effects of α-Lipoic Acid Administration on Plasma Glucose Levels, Total Malondialdehyde Values and Withdrawal Signs in Rats Treated with Morphine or Morphine plus Naloxone

Morphine (CAS 57-27-2) administration or its removal induces alterations in glucose levels and oxidative status or behaviour signs, which may be hypothetically closely related; if this is correct, controlling glucose changes may lead to modifications in peroxide levels and in behaviour profile. It therefore seems important to find a drug able to control alterations of glucose metabolism, peroxide generation and behaviour symptoms in morphine or morphine withdrawal animals. This paper describes the effects of morphine or morphine plus naloxone (CAS 51481-60-8) on the plasma levels of glucose, malondialdehyde (MDA) (CAS 100683-54-3) and behavioural signs in rats treated or not with alpha-lipoic acid (CAS 1077-28-7), known to interfere with glucose and peroxide levels. The administration of morphine or its removal by naloxone alters plasma glucose levels, increases MDA values, and also affects signs such as pain threshold values, fecal excretion and jumping behaviour. The injection of alpha-lipoic acid decreases glycemia in rats treated with morphine or morphine plus naloxone. This result may be due to the capacity of alpha-lipoic acid to facilitate glucose transport and its utilization. The administration of a-lipoic acid to rats given morphine or morphine plus naloxone lowers total MDA levels because of its peroxide scavenging capacity. In animals injected with morphine plus naloxone, which show altered pain thresholds, high fecal excretion and jumping behaviour, treatment with alpha-lipoic acid increases latency times, decreases fecal excretion and reduces jumping. These effects can be attributed to the capacity of alpha-lipoic acid to interfere with mediators or peroxides involved in the modified behaviour. The glycemia levels, MDA values and behavioural signs seem to be interconnected in the reported experiments. The administration of alpha-lipoic acid is demonstrated to control the alterations in plasma glucose levels, peroxide values or behavioural profile in animals receiving morphine or morphine plus naloxone.

Plasma markers of oxidative stress, inflammation and endothelial cell injury in diabetic patients with overt nephropathy administered alpha-lipoic acid and angiotensin II receptor blocker

Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen species (ROS) and regenerates endogenous antioxidants. In the present study, plasma molecular markers of oxidative stress, inflammatory state, and endothelial cell injury was measured to investigate the effect of simultaneous blocking of both angiotensin (AT) II-and oxidative stress-mediated pathophysiologic pathways during the course of type II diabetic nephropathy in the clinical settings. Sixty-three diabetic subjects have carried out either of 12-month treatment course of AT-II receptor blocker (ARB) alone, ALA alone, or combination of both. Plasma malondialdehyde (MDA) level, a marker for oxidative stress, increased in ARB alone group whereas reduced to significantly lower level in ALA+ ARB combination group. Plasma hs-CRP level, an inflammatory marker, decreased significantly in ARB +ALA group. Plasma thrombomodulin (TM) level, a marker of endothelial cell injury, increased in both ARB and ALA group. Twenty-four hour urinary protein excretion, as a marker of renal injury, decreased in ARB and ARB+ALA group. Finally, renal function was reserved well in ARB+ALA group in compared to others. The combined administration of ALA and ARB additively attenuated or reduced plasma markers of oxidative stress, inflammation and endothelial cell injury for one year. It suggests that the benefits in attenuating atherogenic process and vascular injury retard the progression of renal dysfunction.

Choline supplementation reduces oxidative stress in mouse model of allergic airway disease

Asthma is a multi-factorial inflammatory disease associated with increased oxidative stress and altered antioxidant defences. We have evaluated the effect of choline on oxidative stress in a mouse model of airway disease. Balb/c mice were sensitised with 100 microg of ovalbumin on days 0 and 14, and challenged with aerosolized ovalbumin on days 25-27. Mice were administered 1 mg kg(-1) of choline via oral gavage or intranasal route on days 14-27. Mice were also administered 100 mg kg(-1) of alpha-lipoic acid as standard antioxidant. Total cell counts, eosinophils and eosinophil peroxidase (EPO) activity were determined in bronchoalveolar lavage (BAL) fluid. Reactive oxygen species (ROS), lipid peroxidation and isoprostanes levels were measured in BAL fluid. IL-13 and tumour necrosis factor-alpha (TNF-alpha) levels were also measured in BAL fluid and spleen cell culture supernatant. Nuclear factor kappaB (NFkappaB) p65 protein expression was measured after last ovalbumin challenge in nuclear and cytosolic extracts of lungs. Compared with ovalbumin-challenged mice, choline and alpha-lipoic acid treated mice had significantly reduced eosinophilic infiltration and EPO activity in BAL fluid. Choline and alpha-lipoic acid treatment reduced ROS production and isoprostanes level significantly in BAL fluid and thus suppressed oxidative stress. Choline and alpha-lipoic acid administration by either route decreased lipid peroxidation levels and down regulated NFkappaB activity. Further, choline and/or alpha-lipoic acid treatment suppressed TNF-alpha level significantly as compared with that of ovalbumin-challenged mice. Choline administration reduces oxidative stress possibly by modulating the redox status of the cell and inhibits inflammatory response in a mouse model.

MiRNAs expression profiles during ErbB2 driven mammary carcinogenesis

Osteoporosis is a high mortality and morbidity ranged skeletal disease and results in high costs of medical care in the European Union. We evaluated the possible protective effect of alpha-lipoic acid (ALA) on rat bone metabolism in ovariectomy and inflammation-mediated osteoporosis models. Groups were designed as: (1) sham; (2) sham+inflammation; (3) ovariectomy (OVX); (4) ovariectomy+ALA—25 mg/kg; (5) ovariectomy+ALA—50 mg/kg; (6) ovariectomy+inflammation; (7) ovariectomy+inflammation+ALA—25 mg/kg; and (8) ovariectomy+inflammation+ALA—50 mg/kg groups. OVX groups were allowed to recover for two months. Then, inflammation was induced in inflammation groups by subcutaneous talc injection. ALA—25 mg/kg and 50 mg/kg were administered to drug groups chronically. The skeletal response was assessed by bone mineral density (BMD), osteopontin and osteocalcin measurements. Pro-inflammatory cytokine measurements (interleukin (IL)-1beta, interleukin-6, and tumor necrosis factor-alpha) were performed to observe inflammatory process. In OVX, INF and OVX+INF groups, BMD levels were lowest and osteocalcin, osteopontin, IL-1beta, IL-6, and TNF-alpha levels were highest when compared to sham group. ALA administration increased BMD levels and decreased osteocalcin, osteopontin, IL-1beta, IL-6, and TNF-alpha levels versus OVX and OVX+INF control groups. Both in senile and postmenopausal osteoporosis, the balance in coupling were destroyed on behalf of bone resorption. ALA had a protective effect on both senile and postmenopausal osteoporosis. The positive effect of this drug in these osteoporosis models might originate from its positive effects on bone turnover markers and cytokine levels. From this perspective, ALA may be a candidate for radical osteoporosis treatment both in senile and postmenopausal types clinically at the end of advanced studies.