Lipoic Acid Group Research Articles

Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats

Objective: To see the Effects of Alpha-Lipoic Acid (ALA) supplementation on slow skeletal muscle mass andcontractile functions in type 2 diabetic male Sprague Dawley rats.Study Design: Quasi-experimental study.Place and Duration of Study: The study was carried out at the Physiology Research Lab, Army MedicalCollege, Rawalpindi, Pakistan from June 2019 to April 2021 in collaboration with the National Institute of Health(NIH) Islamabad, Pakistan.Methods: Sixty adult SD rats were divided into three equal groups. Rats were fed on a standard diet as per NIHprotocols. After 2 weeks type 2 Diabetes mellitus (T2DM) was induced in groups 2 and 3 by injecting low dose35mg of streptozotocin (STZ) in the abdomen intraperitoneally. T2DM was successfully developed andconfirmed by measuring glucose levels through a glucometer. Group 3 was injected with Alpha Lipoic acid30mg/kg/day at the lower abdomen for the next two weeks. After 04 weeks, soleus muscles were dissected.The animal data acquisition unit (iWorx) was used for assessing the contractile functions of soleus.Results: Alpha Lipoic acid group showed improvement in muscle mass, muscle tension strength, and recoveryfrom fatigue after applying fatigue protocol as compared to group 2.Conclusion: Alpha Lipoic acid supplementation improves contractile force and delays fatigue in the soleusmuscles of diabetic rats. How to cite this: Khan BU, Yousef I, Arshad S, Ikram F, Ali A, Ullah I. Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats. Life and Science. 2024; 5(2): 216-221. doi: http://doi.org/10.37185/LnS.1.1.408

Effect of Alpha Lipoic Acid and Pyridine Group on Silicone Hydrogel Lens

Effect of Alpha Lipoic Acid and Pyridine Group on Silicone Hydrogel Lens

Effects of antioxidant alfa-lipolic acid on polyphenol oxidase activity of acitretin- methotrexate combination in rat spleen tissue

Objectives: Acitretin, a lipophilic weak acid, is a slightly water-soluble vitamin A analog. Methotrexate is a folic acid analogue and an antimetabolite used for the treatment of many diseases.. Alpha lipoic acid is a nutritional coenzyme with important physiological effects in protein, fat and carbohydrate metabolism. Polyphenol oxidase is an oxidoreductase containing copper in its active site and oxidizes phenolic compounds. The aim of this study is to determine the effect of Alpha lipoic acid on the polyphenol oxidase enzyme activity in the spleen tissue in removing the damage caused by the free radicals produced by Acitretin and Methotrexate at the cellular level. Materials and Methods: Study groups were formed as Control , Alpha lipoic acid , Acitretin+Methotrexate and Acitretin+Methotrexate+Alpha lipoic acid groups. Rats who were starved for 24 hours were injected at the every morning. Acitretin, Methotrexate and Alpha Lipoic Acid were dissolved in 0.9% NaCl and given to rats by intraperitoneal injection. Rats were sacrificed by cervical dislocation on the 7th day after injection. After perfusion of the heart, the spleen was removed. Extracted spleen tissue samples were used for polyphenol oxidase enzyme activity determination. Results: Results: Compared with groups Control; While 18% inhibition was observed in the Alpha lipoic acid group, 20% inhibition was observed in the Acitretin + Methotrexate group. When Alpha lipoic acid was added to the Acitretin + Methotrexate group, while 19% activation was observed according to Control, 1% activation was observed compared to the Acitretin+Methotrexate group. Although there were differences between the groups, these differences were not statistically significant. Conclusion: The inhibition of PPO enzyme activity by ALA can be explained by the fact that while ALA alone acts as a radical scavenger that can regenerate substances with antioxidant properties in the spleen tissue, when given in combination, it acts as an antioxidant that triggers PPO activity.

Protective Effects of Alpha Lipoic Acid Against Ionizing Radiation- Induced Hepatotoxicity in Rats.

Radiation is used to treat cancer but causes serious complications, such as liver toxicity. In this study, the protective effects of alpha lipoic acid against the unwanted effects of radiation used in many cancer treatments which can cause damage after treatment were investigated. The sample consisted of 32 Sprague-Dawley male rats randomized equally into 4 groups. The control group received no intervention. The alpha lipoic acid group was administered 50 mg/kg (dissolved in 0.9% NaCl) for 3 days. The ionizing radiation group was exposed to a total of 30 Gy radiation in 10 Gy fractions per day. The ionizing radiation+alpha lipoic acid group was administered 50 mg/kg alpha lipoic acid® prior to exposure to a total of 30 Gy radiation in 10 Gy fractions per day. Rats were sacrificed by cervical dislocation, and the liver was removed for histopathological studies and superoxide dismutase and malondialdehyde assays. Liver tissues were histopathologically assessed using hematoxylin-eosin staining after 4 weeks of the experiment. The ionizing radiation + alpha lipoic acid group had significantly less severe necrosis than the ionizing radiation group. Compared to the ionizing radiation group and the ionizing radiation + alpha lipoic acid group, superoxide dismutase enzyme activity was decreased with the addition of alpha lipoic acid. In addition, when the amount of malondialdehyde, which is a marker of oxidative stress, was examined, it was determined that the amount of malondialdehyde in the ionizing radiation + alpha lipoic acid group was lower than in the ionizing radiation Group. Alpha lipoic acid® mitigates radiotherapy-induced damage in liver tissue.

The comparison of alpha lipoic acid with methylprednisolone and sucralfate in subacute wound healing corrosive esophagus-induced rats: An experimental study.

This study aims to compare methylprednisolone frequently used in the therapeutic practices of corrosive esophagus burns, sucralfate, a protective material of mucosal surfaces, and alpha lipoic acid, the most potent antioxidant in a rat model. A total of 40 female Sprague-Dawley rats were used in this study. The rats were equally divided into control, alpha lipoic acid, methylprednisolone, and sucralfate groups (n=10). A corrosive esophagus burn was created by using 10% pH:12 sodium hydroxide. No treatment was applied to the control group, and each group was given their own treatment. The treatment was continued regularly until the eighth day, when they were sacrificed. The corrosive esophagus burn lines were removed and tissue sections were stained with hematoxylin and eosin. The difference in ulceration in the group treated with alpha lipoic acid was significant, compared to the other groups. The most excellent complete epithelialization and complete re-epithelialization were observed in the alpha lipoic acid group. The difference between the groups was significant, with complete re-epithelialization being the lowest in the control and methylprednisolone groups (42.9% and 12.5%, respectively) and the highest in the alpha lipoic acid group (77.8%). In terms of ulceration and re-epithelialization, comparable values were found in the alpha lipoic acid group. The main difference was that the inflammation levels in the sucralfate group were lower and more favorable than the other groups in this period. The glutathione level was significantly higher in the alpha lipoic acid group and decreased the tissue hydroxyproline level. Alpha lipoic acid reduces esophageal ulceration, severity and prevalence of inflammation, severity and prevalence of fibrosis, decreases tissue damage by increasing blood glutathione level, and also reduces stricture in corrosive esophagus burns in rats.

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).

Growth variables, feed efficacy, survival rate, and antioxidant capacity of European seabass (Dicentrarchus labrax L.) larvae treated with Coenzyme Q10 or lipoic acid

A 30-day feeding trial was performed to assess the potential of the dietary supplementation of Coenzyme Q10 (CoQ10) and lipoic acid on acclimatized European seabass larvae with a preliminary weight and length of 2.7 mg and 12.42 mm (25 dph = days post-hatching). Seven experimental groups were fed on the basal micro-diet (56 % crude protein and 13 % crude lipid) without any supplement in the control group or with the addition of CoQ10 at levels of 5, 10, and 15 mg/kg or α-lipoic acid at levels of 50, 100, and 150 mg/kg, respectively. Larvae fed on a diet enriched with CoQ10 at levels of 5 and 10 mg/kg showed the highest values for final weight, weight gain, specific growth rate (SGR), the protein efficiency ratio (PER), and the lowest value for feed conversion ratio (FCR) as well as no morphological or histological abnormalities. Also, the group fed a diet supplemented with CoQ10 at 5 mg/kg gave the highest values for final length and survival. The survival rate ranged from 54.59 % to 79.82 % and the lowest rate was in the group fed a diet enhanced with lipoic acid at 150 mg/kg. Meanwhile, the lowest records for final weight, weight gain, protein efficiency ratio, and the presence of morphological and histological abnormalities were in groups fed on the control diet and with high levels of lipoic acids (100 and 150 mg/kg). Moreover, all lipoic acid groups showed deleterious signs in the histological structure of the intestine and liver. However, significantly lower values of catalase (CAT) and glutathione peroxidase (GPx) were found in the fish group fed on the basal diet, while the peak values were in groups fed on diets fortified with CoQ10 at 5 and 10 mg/kg. In addition, larvae fed CoQ10 at levels of 5 or 10 mg/kg performed better in terms of CAT and GPx activities than that fed lipoic acid at levels of 100 or 150 mg/kg. Furthermore, the control group displayed lower levels of insulin-like growth factor 1 (IGF-1), CAT, and GPx -related gene expressions while considerable upregulations of IGF-1 and GPx were noted in larvae groups fed on diets improved with CoQ10 at levels of 5 or 10 mg/kg and lipoic acid at 50 mg/kg compared to the others. Also, upregulations in CAT were found with CoQ10 at levels of 5 or 10 mg/kg compared to their counterparts in the other groups. In conclusion, dietary CoQ10 at 5 or 10 mg/kg improves the performance and well-being of European seabass.

Potential effects of Alpha lipoic acid on behavioral alteration and glutamate accumulation during d-gal-induced brain aging in male rats

Background: Alpha lipoic acid has both hydrophilic and hydrophobic characteristics and is abundantly distributed in cellular membranes and the cytoplasm. It is among the top cell- protective antioxidants. Material and methods : The present work investigated the possible therapeutic effects of alpha lipoic acid in a male rat model of brain aging induced by D-galactose. Four equal-sized groups of 40 male rats were randomly assigned: G1, the control group, G2, and G3, which each received daily doses of 200 mg/kg of D-gal for 30 days. Alpha lipoic acid was given orally for 30 days to the G4 D-gal + alpha lipoic acid group at 200 mg/kg bw, IP. daily with 100 mg/kg. thirty days of IP. Glutamate is deposited in the brain, according to research on behavioral alterations and brain glutamate. Indicators of oxidative stress are increased Our Results show that whereas brain glutamate deposition declines in the D-gal model of aging, the Forced Swimming Test (FST) and Morris Water Maze Test considerably rise (MWM).

Lipoic acid inhibits nerve cell apoptosis in rats with Parkinson's disease via Erk signaling pathway

Purpose: To investigate the effect of lipoic acid on nerve cell apoptosis in rats with Parkinson's disease via the extracellular signal-regulated kinase (ERK) signaling pathway.Methods: A total of 36 rats were randomly divided into normal group (n = 12), Parkinson's disease model group (n = 12) and lipoic acid group (n = 12). The neuronal morphology was examined by means of Nissl staining, while cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.Results: The neurons were severely damaged in model group, while neuronal morphology and structure were ameliorated in lipoic acid group when compared with those in model group. The p-ERK was lowered significantly (p &lt; 0.05) in model group and lipoic acid group compared with that in normal group. Levels of mRNA, caspase-3 and Bax increased significantly, while Bcl-2 decreased in model group and lipoic acid group when compared with those in normal group (p &lt; 0.05). Lipoic acid treatment significantly reduced mRNA expression of caspase-3 and Bax, but increased Bcl-2 compared with model group. Furthermore, ELISA results indicate that model and lipoic acid groups exhibited raised caspase-3 and Bax but significantly reduced Bcl-2 levels, compared with normal group. The results also showed that the apoptosis was higher in the other two groups than in normal group; on the other hand, it was significantly lower in lipoic acid group than in model group (p &lt; 0.05).Conclusion: Lipoic acid inhibits nerve cell apoptosis in rats with Parkinson's disease by up-regulating ERK signaling pathway. Therefore, lipoic acid is a potential neuroprotective agent for the management of Parkinson’s disease.

Efficacy of Alpha Lipoic Acid Supplementation In Chemotherapy-Induced Peripheral Neuropathy

A B S T R A C TBackground. Chemotherapy-induced peripheral neuropathy is a side effect ofseveral chemotherapy drugs and a significant cause of chronic pain in cancerpatients, which affects patients' long-term quality of life. The neurotoxicchemotherapy agents most reported to cause neuropathic pains are platinum andtaxane. This study aimed to determine the efficacy of alpha-lipoic acidsupplementation in chemotherapy patients. Methods. This study used arandomized, double-blind clinical trial in the oncology haematology clinic in theDepartment of Internal Medicine at Mohammad Hoesin General Hospital Palembangfrom November 2018 to July 2019. Samples were taken from patients who met theinclusion criteria and signed informed consent forms to join the study. This studyused SPSS version 22.0 for Windows to analyze the data.Results. This researchstudied 30 subjects who were divided into alpha lipoic acid groups and placebogroups with 15 samples each. The alpha-lipoic acid group showed a significantdecline in the Toronto Clinical Scoring System (TCSS) after treatment (p = 0.000)compared to the placebo group (p = 0.164). Conclusions. Treatment with a 600 mgsingle dose each day of alpha-lipoic acid for 12 weeks effectively improved patientscondition significantly.

Partially saturated canthaxanthin alleviates aging-associated oxidative stress in D-galactose administered male wistar rats.

It has been earlier reported that partially saturated canthaxanthin (PSC) from Aspergillus carbonarius mutant is non-toxic, has anti-lipid peroxidation activity and can induce apoptosis in prostate cancer cell lines. In the present study, the antiaging effect of PSC was explored in D-galactose administered male wistar rats. 8-10 weeks old, male wistar rats were randomly divided into (i) Vehicle Control Group (VCG), (ii) Aged Control Group (ACG), (iii) Aged + α Lipoic Acid Group (ALG) and (iv) Aged + Partially saturated canthaxanthin Group (APG). Rats received D-galactose (300mg /kg bwt/day; i.p.) alone (ACG) or together with PSC (APG) (20mg/kg bwt/day; oral) and α Lipoic Acid (ALG) (80mg/kg bwt/day; oral) for 10 weeks. Rats in VCG were injected with the same volume of physiological saline (i.p.) and fed with olive oil (vehicle). In vitro protein oxidation and DNA oxidation inhibition, in vivo malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities were determined. In addition, brain neurotransmitters, dopamine and serotonin were estimated by NMR. PSC treatment showed inhibition against protein and DNA oxidation. PSC effectively improved D-galactose induced aging rats by inducing a protective effect through up-regulation of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and brain neurotransmitters and downregulated malondialdehyde (MDA) and monoamineoxidase (MAO) levels. Thus, PSC appears to be a functional compound having antioxidant and antiaging properties.

Lipoic Acid Decreases the Expression of Poly ADP-Ribose Polymerase and Inhibits Apoptosis in Diabetic Rats.

PurposeTo study the effects of lipoic acid on poly ADP-ribose polymerase (PARP) expression and apoptosis in diabetic rats.Materials and MethodsSprague–Dawley rats (n=30) with high-fat diet- and streptozotocin-induced diabetes were randomly divided into two groups: diabetic model (DM) group and lipoic acid (LA) treatment group; another 10 rats were selected as normal controls (NC). The serum levels of 8-hydroxy-2ʹ-deoxyguanosine, nitrotyrosine, and 8-isoprostane; sciatic nerve cell apoptosis index; and PARP expression were detected in the rats, and morphological changes in the sciatic nerve were recorded.ResultsThe blood glucose level in the DM and LA groups was significantly higher than that of the NC group (P<0.01). Compared to the NC group, the DM group showed demyelinating changes to sciatic nerve fibers. PARP expression; serum levels of 8-hydroxy-2-deoxyguanosine, nitrotyrosine, and 8-isoprostane; and the apoptosis index of sciatic nerve cells were significantly higher than those of the NC group (P<0. 01). Following LA treatment, the above indices showed significant improvement (P<0.01).ConclusionLipoic acid may improve the symptoms of diabetic neuropathy by reducing PARP activity and inhibiting apoptosis.

The Feasibility of Blood Pressure Control with Autonomic- Assisted Hypertension Therapy versus JNC 8 Therapy

Background: Over one billion people have Hypertension (HTN); mortality and morbidity are increasing. The Parasympathetic and Sympathetic (P&amp;S) nervous systems prominently affect the onset and progression of HTN, yet P&amp;S measures are not used to assist in management. Our objective was to determine the feasibility of HTN control using P&amp;S-guided to JNC 8 HTN therapy. Methods: 46 uncontrolled HTN patients were randomized prospectively to P&amp;S-assisted management, adjusting JNC 8 therapy using the ANX 3.0 Autonomic Monitor and adding (r) Alpha Lipoic Acid (Group 1) vs. JNC 8 (Group 2). Results: The two Groups were similar in: 1) age (mean 66 vs. 70 y/o for Groups 1 and 2, respectively; 2) initial resting home Blood Pressure (BP, Group 1 mean=162/90 mmHg vs. Group 2 mean=166/87 mmHg, 3) initial resting office BP Group 1 mean=151/75 mmHg vs. Group 2 mean=155/73 mmHg, and 4) ethnicity. Upon follow-up (mean=8.35 mo.): 1) mean resting home BPs were 145/77 mmHg (Group 1, 74% of patients at JNC 8 goal) vs. 155/83.5 mmHg (Group 2, 30.4% at JNC 8 goal), and 2) mean resting office BPs were 138/71 mmHg (Group 1) vs. 146/65 mmHg (Group 2). At the study’s conclusion, Group 1 Sympathetic tone was lower than that for Group 2 both at rest and upon standing, and Group 1 Parasympathetic tone was higher than that for Group 2 both at rest and upon standing. Conclusion: P&amp;S-assisted HTN therapy is feasible, resulting in improved BP control, through healthier P&amp;S tone on fewer prescription medications.

Effects of Alpha Lipoic Acid Supplementation on Serum Levels of Oxidative Stress, Inflammatory Markers and Clinical Prognosis among Acute Ischemic Stroke Patients: A Randomized, Double Blind, TNS Trial.

Purpose: Stroke is one of the most common conditions causing death. There have been few studies examining the effects of alpha lipoic acid (ALA) on stroke patients. In this regard, the present randomized controlled clinical trial was conducted to examine the effects of ALA supplementation on serum albumin, and inflammatory and oxidative stress markers in stroke patients. Methods: The present paralleled randomized controlled clinical trial involved 42 stroke patients who were over 40 years and under enteral feeding. The participants were randomly assigned into two groups and finally 40 patients completed the study. Patients in alpha lipoic acid group (n=19) took 1200 mg ALA supplement daily along with their meal, and participants in control group (n=21) underwent the routine hospital diet for 3 weeks. Fasting blood samples were obtained and albumin, oxidative stress, and inflammatory indices were assessed at baseline, as well as at the end of the trial. Results: After 3 weeks, treatment of patients with ALA led to a significant decrease in tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels (P=0.01) compared to baseline. But serum levels of albumin, total antioxidant capacity (TAC), malondialdehyde (MDA), highsensitivity C-reactive protein (hs-CRP), IL-6 and TNF-α did not change significantly vs. control group (P>0.05). Conclusion: ALA did not significantly change the serum levels of albumin and inflammatory as well as antioxidant capacity indices in stroke patients compared with the control group. More clinical trials with large sample sizes and long duration are needed to clarify the effects of ALA on these patients.

Dual-Receptor-Targeted (DRT) Radiation Nanomedicine Labeled with 177Lu Is More Potent for Killing Human Breast Cancer Cells That Coexpress HER2 and EGFR Than Single-Receptor-Targeted (SRT) Radiation Nanomedicines.

Resistance to HER2-targeted therapies in breast cancer (BC) is associated in some cases with an increased expression of epidermal growth factor receptors (EGFR). We describe a dual-receptor-targeted (DRT) radiation nanomedicine for local intratumoral (i.t.) treatment of BC composed of 15 nm sized gold nanoparticles (AuNPs) modified with trastuzumab (TmAb) to target HER2 and panitumumab (PmAb) to target EGFR. The AuNPs were modified with poly(ethylene glycol) (PEG3k) linked to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators to complex the β-particle emitter, 177Lu. Our aim was to compare the properties of these DRT-AuNP-177Lu with single-receptor-targeted (SRT)-TmAb-AuNP-177Lu or PmAb-AuNP-177Lu or nontargeted (NT)-AuNP-177Lu using human BC cells that expressed HER2, EGFR, or both receptors. To construct these radiation nanomedicines, PEG5K was linked to TmAb or PmAb, while PEG3k was linked to DOTA. These polymers were conjugated to AuNP via two Au-thiol bonds using a terminal lipoic acid (LA) group on the polymers. NT-AuNP-177Lu were constructed without modification with TmAb or PmAb. MDA-MB-231-H2N, MDA-MB-468, and BT-474 human BC cells were designated as HER2mod/EGFRmod, EGFRhigh/HER2neg, and HER2high/EGFRlow, respectively, based on the expression of these receptors. Specific binding to HER2 and/or EGFR was assessed by incubating BC cells with DRT-AuNP-177Lu or TmAb-AuNP-177Lu or PmAb-AuNP-177Lu, or NT-AuNP-177Lu in the absence or presence of an excess of TmAb or PmAb or both competitors. Binding and internalization of AuNP by BC cells were assessed by dark-field microscopy. Cell fractionation studies were conducted to quantify AuNP-177Lu bound and internalized. The cytotoxicity of DRT-AuNP-177Lu was determined in clonogenic survival (CS) assays after an exposure of 5 × 105 BC cells to 3 MBq (1.4 × 1012 AuNP) for 16 h and then seeding and culturing the cells for 7-15 days. CS was compared to exposure to TmAb-AuNP-177Lu and PmAb-AuNP-177Lu or NT-AuNP-177Lu. The absorbed doses to the nucleus in these CS assays were estimated. DRT-AuNP-177Lu were specifically bound by BC cells that expressed HER2 or EGFR or both receptors. In contrast, SRT-TmAb-AuNP-177Lu and PmAb-AuNP-177Lu were bound and internalized only by BC cells that expressed HER2 or EGFR, respectively. NT-AuNP-177Lu exhibited very low binding to BC cells. DRT-AuNP-177Lu and SRT-TmAb-AuNP-177Lu or PmAb-AuNP-177Lu were internalized by BC cells in accordance with the receptor expression. Importantly, DRT-AuNP-177Lu were more potent in vitro than PmAb-AuNP-177Lu for killing MDA-MB-231-H2N cells that coexpress HER2 and EGFR (CS = 18.8 ± 1.0 vs 51.5 ± 10.4%; P = 0.006). Furthermore, DRT-AuNP-177Lu were more potent for killing BT-474 cells with high HER2 but low EGFR expression than TmAb-AuNP-177Lu (CS = 8.9 ± 3.3 vs 20.7 ± 2.4%; P = 0.007) or PmAb-AuNP-177Lu (CS = 63.9 ± 1.7%; P < 0.0001). Even for MDA-MB-468 cells that overexpress EGFR but have negligible HER2, DRT-AuNP-177Lu were more potent for cell killing than PmAb-AuNP-177Lu (CS = 3.2 ± 3.0 vs 7.5 ± 1.8%; P = 0.001) or TmAb-AuNP-177Lu (63.2 ± 3.2%; P = 0.0002). All targeted forms of AuNP-177Lu were more cytotoxic to BC cells than those of NT-AuNP-177Lu. High absorbed doses (36-119 Gy) were deposited in the nucleus of BC cells by DRT-AuNP-177Lu. We conclude that a DRT radiation nanomedicine is more potent for killing BC cells that coexpress HER2 and EGFR than SRT radiation nanomedicines. These results are promising for further evaluation of these DRT-AuNP-177Lu in vivo for the local radiation treatment of human BC tumors that coexpress HER2 and EGFR in mice following i.t. injection, especially tumors that are resistant to HER2-targeted therapies.

The Feasibility of Blood Pressure Control with Autonomic-Assisted Hypertension Therapy Versus JNC 8 Therapy

Background: Over one billion people have Hypertension (HTN); mortality and morbidity are increasing. The Parasympathetic and Sympathetic (P&amp;S) nervous systems prominently affect the onset and progression of HTN, yet P&amp;S measures are not used to assist in management. Our objective was to determine the feasibility of HTN control using P&amp;S-guided to JNC 8 HTN therapy. Methods: 46 uncontrolled HTN patients were randomized prospectively to P&amp;S-assisted management, adjusting JNC 8 therapy using the ANX 3.0 Autonomic Monitor and adding (r) Alpha Lipoic Acid (Group 1) vs. JNC 8 (Group 2). Results: The two Groups were similar in: 1) age (mean 66 vs. 70 y/o for Groups 1 and 2, respectively; 2) initial resting home Blood Pressure (BP, Group 1 mean=162/90 mmHg vs. Group 2 mean=166/87 mmHg, 3) initial resting office BP Group 1 mean=151/75 mmHg vs. Group 2 mean=155/73 mmHg, and 4) ethnicity. Upon follow-up (mean=8.35 mo.): 1) mean resting home BPs were 145/77 mmHg (Group 1, 74% of patients at JNC 8 goal) vs. 155/83.5 mmHg (Group 2, 30.4% at JNC 8 goal), and 2) mean resting office BPs were 138/71 mmHg (Group 1) vs. 146/65 mmHg (Group 2). At the studys conclusion, Group 1 Sympathetic tone was lower than that for Group 2 both at rest and upon standing, and Group 1 Parasympathetic tone was higher than that for Group 2 both at rest and upon standing. Conclusion: P&amp;S-assisted HTN therapy is feasible, resulting in improved BP control, through healthier P&amp;S tone on fewer prescription medications.

The dual-function of lipoic acid groups as surface anchors and sulfhydryl reactive sites on polymer-stabilized QDs and Au nanocolloids.

Coating inorganic nanocrystals [e.g., quantum dots (QDs) and gold nanoparticles] with polymer ligands presenting multiple lipoic acid anchoring groups provides nanocolloids with remarkable long-term colloidal and photophysical stability. Here, we show that the natural swelling of macromolecules leaves a fraction of the lipoic acid groups in the surface coating free, which are targeted for activation and conjugation to target molecules, using the reliable sulfhydryl-to-maleimide reaction. This implies that simple and efficient functionalization of the nanocrystals can be achieved without introducing additional reactive groups in the coating. We apply a photomediated ligand exchange strategy to luminescent QDs and AuNPs and react the resulting nanocrystals with maleimide Cy3 dye. We then use optical absorption and resonance energy transfer measurements applied to QD-Cy3 and AuNP-Cy3 conjugates to extract estimates for the fraction of accessible lipoic acid groups per QD or AuNP. In addition, we demonstrate the potential utility of this approach by constructing a ratiometric pH sensor made of QD-SNARF conjugates. Our ligand design combined with the photoligation strategy yield colloidally stable dispersions of QDs and AuNPs that present accessible reactive thiols, without introducing new functionalities or requiring disulfide reducing reagents, making them useful for potential use in applications such as biological sensing and imaging.

Protective effect of alpha lipoic acid on diabetic nephropathy in rats

Objective: To evaluate the protective role of alpha lipoic acid in rats affected with experimentally-induced diabetes and secondarily complicated with nephropathy. Design: Randomized controlled study. Animals: Forty-eight Sprague Dawley rats. Procedures: Rats were allocated randomly into four groups (12 each); Control rats (Group 1); alpha lipoic acid (ALA) supplemented rats (Group 2); rats with induced diabetic nephropathy (Group 3), and rats with diabetic nephropathy and supplemented with alpha lipoic acid (Group 4). After one month of experimental induction, serum, plasma and renal tissue samples were harvested to determine glycemic status, renal damage markers, antioxidant status, oxidative and nitrosative stress markers, apoptotic marker and histopathology of kidney tissues. Results: In comparison with non-supplemented diabetic rats, alpha lipoic acid reduced renal malondialdehyde (5.74± 0.26 vs 11.3± 1.96 nmol/g. tissue) and renal nitric oxide (30.06± 2.07 vs 36.6± 1.07 nmol/g. tissue). ALA significantly improved the antioxidant enzyme activity (catalase and reduced glutathione), glycemic status, and decreased caspase 3 concentration (P<0.05). Conclusion and clinical relevance: Alpha lipoic acid may be an alternative intervention to alleviate nephropathy as a complication of diabetes. Further studies need to be done in naturally occurring cases.

Influence of Trolox and Alpha-Lipoic Acid on Post-Thawed Pırlak Ram Sperm Parameters, Oxidative Stress and DNA Damage in Non-Breeding Season

The present study was conducted to examine the protective roles of trolox and alpha-lipoic on post-thawed Pirlak ram sperm parameters, oxidative stress and DNA damage in non-breeding season. Semen samples from 5 healty Pırlak rams (2-3 years of age) were used in the study. Six ejaculates for each rams were collected and pooled. Ejaculates were split into three aliquots and diluted to a final concentration of 150x106 spermatozoa/ml with the base extender containing 1 mM alpha lipoic acid, 1 mM trolox and no additive (control) were cooled to 5 °C and equilibrated for 3 h then frozen in 0.25 ml French straws. Samples were thawed in 37 oC and evaluated in terms of spermatological parameters, DNA damage, oxidative stress. Sperm motility was increased, acrosome rate and DNA damage were decreased significantly (p<0.05) in ALA, head abnormal sperm rate and membrane integrity were increased, acrosome rate and DNA damege were decreased significantly (P < 0.05) in trolox when compared to the control group. Compared with the control group, reductions in spermatozoon MDA and GSH levels were statistically significant (P <0.05) in lipoic acid and trolox groups. Results of this study suggest that alpha-lipoic acid and trolox improve sperm parmeters, oxidative stress and DNA damage in non-breeding season.

Protective effect of alpha lipoic acid on diabetic nephropathy in rats

Objective: To evaluate the protective role of alpha lipoic acid in rats affected with experimentally-induced diabetes and secondarily complicated with nephropathy. Design: Randomized controlled study. Animals: Forty-eight Sprague Dawley rats. Procedures: Rats were allocated randomly into four groups (12 each); Control rats (Group 1); alpha lipoic acid (ALA) supplemented rats (Group 2); rats with induced diabetic nephropathy (Group 3), and rats with diabetic nephropathy and supplemented with alpha lipoic acid (Group 4). After one month of experimental induction, serum, plasma and renal tissue samples were harvested to determine glycemic status, renal damage markers, antioxidant status, oxidative and nitrosative stress markers, apoptotic marker and histopathology of kidney tissues. Results: In comparison with non-supplemented diabetic rats, alpha lipoic acid reduced renal malondialdehyde (5.74± 0.26 vs 11.3± 1.96 nmol/g. tissue) and renal nitric oxide (30.06± 2.07 vs 36.6± 1.07 nmol/g. tissue). ALA significantly improved the antioxidant enzyme activity (catalase and reduced glutathione), glycemic status, and decreased caspase 3 concentration (P&lt;0.05). Conclusion and clinical relevance: Alpha lipoic acid may be an alternative intervention to alleviate nephropathy as a complication of diabetes. Further studies need to be done in naturally occurring cases.