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Effect of alpha lipoic acid in treatment of type 2 diabetes


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Objective: Antioxidant probably can prevent the progression and complications of Type 2 diabetes mellitus (T2DM). Due to effectiveness of alpha lipoic acid (ALA) as an antioxidant, this study was done in T2DM patients to evaluate the effect of ALA on their diabetic status, lipid profile, and oxidative stress (OS) status.Methods: A total of 35 patients with diabetes were selected randomly who were under insulin treatment mainly and grouped as Group “A.” Another age- and sex-matched healthy controls selected grouped as “B.” Both groups supplemented with ALA (300 mg/day) for 6 months continuously. All parameters were tested before and after the supplementation.Results: There was a significant decrease in fasting blood sugar from 161 to 122 mg/dl in Group “A” and from 98 to 90 mg/dl in Group “B.” Postprandial blood sugar (PPBS) and glycosylated hemoglobin (HbA1c) levels also significantly decreased from 211 to 158 mg/dl and 8.81% to 7.2%, respectively, in Group “A.” PPBS levels significantly decreased from 130 to 124 mg/dl in Group “B,” but HbA1c% decreased insignificantly from 5.26% to 5.24% in Group “B.” Lipid profile parameters decreased in both groups except triglyceride level, which show insignificant relation in Group “B.” OS marker malondialdehyde significantly decreased from 1.967 to 1.592 nm/ml in Group “A” and from 0.613 to 0.472 nm/ml in Group “B.” Plasma antioxidant glutathione shows a significant increase in both groups from 2.117 to 2.405 μmol/L in Group “A” and from 2.631 to 2.811 μmol/L in Group “B.” Plasma nitric oxide also shows significant increase in both groups from 1.712 to 1.990 μmol/L and from 2.139 to 2.318 μmol/L, respectively.Conclusion: Therefore, ALA is a potent antioxidant and can be used against oxidative injury associate with T2DM.
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Vol 10, Issue 8, 2017
Online - 2455-3891
Print - 0974-2441
1Department of Physiology, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, Odisha, India. 2Department of Anatomy, Institute
of Medical Sciences & SUM Hospital, Bhubaneswar, Odisha, India. Email:
Received: 03 April 2017, Revised and Accepted: 03 May 2017
Objective: Antioxidant probably can prevent the progression and complications of Type 2 diabetes mellitus (T2DM). Due to effectiveness of alpha
lipoic acid (ALA) as an antioxidant, this study was done in T2DM patients to evaluate the effect of ALA on their diabetic status, lipid profile, and
oxidative stress (OS) status.
Methods: A total of 35 patients with diabetes were selected randomly who were under insulin treatment mainly and grouped as Group “A.” Another
age- and sex-matched healthy controls selected grouped as “B.” Both groups supplemented with ALA (300 mg/day) for 6 months continuously. All
parameters were tested before and after the supplementation.
Results: There was a significant decrease in fasting blood sugar from 161 to 122 mg/dl in Group “A” and from 98 to 90 mg/dl in Group “B.” Postprandial
blood sugar (PPBS) and glycosylated hemoglobin (HbA1c) levels also significantly decreased from 211 to 158 mg/dl and 8.81% to 7.2%, respectively,
in Group “A.” PPBS levels significantly decreased from 130 to 124 mg/dl in Group “B,” but HbA1c% decreased insignificantly from 5.26% to 5.24%
in Group “B.” Lipid profile parameters decreased in both groups except triglyceride level, which show insignificant relation in Group “B.” OS marker
malondialdehyde significantly decreased from 1.967 to 1.592 nm/ml in Group “A” and from 0.613 to 0.472 nm/ml in Group “B.” Plasma antioxidant
glutathione shows a significant increase in both groups from 2.117 to 2.405 µmol/L in Group “A” and from 2.631 to 2.811 µmol/L in Group “B.” Plasma
nitric oxide also shows significant increase in both groups from 1.712 to 1.990 µmol/L and from 2.139 to 2.318 µmol/L, respectively.
Conclusion: Therefore, ALA is a potent antioxidant and can be used against oxidative injury associate with T2DM.
Keywords: Type 2 diabetes mellitus, Alpha lipoic acid, Oxidative stress markers.
As a chronic metabolic disorder, diabetes mellitus (DM) characterized
by hyperglycemia due to defect in secretion or action of insulin or
both, this causes imbalance in carbohydrate and fat metabolism [1].
DM is mainly categorized into Type 1 and Type 2. Type 1 DM (T1DM)
is primarily due to autoimmune pancreatic ß-cell destruction. Type 2
DM (T2DM) is the frequent form and is due to impaired insulin
secretion or insulin resistance [2]. According to the Diabetes Atlas
2011, the incidence of diabetes is increasing and expected to reach
from 366 million in 2011 to 552 million by 2030 [3]. Due to diversity
of manifestation of disease and its complications, it causes a great
human suffering physically, mentally, and even economically, even
with the enormous available facilities to control the disorder [4]. In
the disease progression, the prolonged exposure to hyperglycemia
causes many long-term microvascular or macrovascular complications
involving cardiovascular system, excretory system, nervous system
causes diabetic cardiomyopathy, diabetic retinopathy, and neuropathy,
which are prime cause of disability, morbidity, and premature death in
T2DM [5,6].
Oxidative stress (OS) results insulin resistance in T2DM [7].
Hence, number of studies done to know the effect of antioxidant
supplementation in T2DM treatment, where some found positive
result [8-10], while others found none [11]. Alpha lipoic acid (ALA) a
both fat and water soluble antioxidant may help in regenerating other
antioxidants and make them active again so often termed as “universal
antioxidant.” ALA might protect metabolic syndromes such as DM,
improving insulin sensitivity and preventing distal sensory-motor
diabetic neuropathy [12]. According to Blumenthal study, ALA in their
experimental study improved the glycemic condition by acting on the
liver [13].
However, there are some inconclusive evidences regarding its action in
defending the OS level, improving the conditions of insulin deficiency
and improvement of lipid profile level in T2DM patients. They are
mostly done on animals [14,15]. As the T2DM incidence is increasing
rapidly, the present study was undertaken to explore the effect of ALA
supplementation on glycemic indexes, lipid profiles, and OS markers in
T2DM patients.
This was a prospective study including patients who were attending
Endocrinology Department (both indoor and outdoor) and their
biomolecular investigations were carried in Physiology Department
and Biochemistry Department, IMS and SUM Hospital, Bhubaneswar.
The institutional ethical committee approval was obtained.
For this study, 35 patients suffering from T2DM were included in Group
A,” who were taking insulin as their main treatment. Moreover, 35
healthy participants were taken as controls, who were matched by age
and gender, grouped as Group “B.” The study protocol was explained to
the patients, and their written consent was obtained. All patients were
supplemented by ALA capsules (133 mg), 2 capsules/day for 6 months
• InclusioncriteriawerepatientswithT2DMwithfastingbloodsugar
(FBS) <250 mg/dl. Moreover, patients taking insulin as their main
• Exclusioncriteria:PatientswithT2DMwhoseFBS>250mg/dl;patients
withuncontrolledhypertension(blood pressure >140/90 mmHg
inspiteofantihypertensivedrugs); patients with complications
ofdiabetesincludingnephropathy, retinopathy,and neuropathy;
patients with any history of myocardial infarction or cardiac
interventionor clinically active cardiovasculardiseases;patients
Research Article
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Panda et al.
withknownrenalor hepatic diseases; and pregnant females,
unwillingness to participate, or mental incapacity to take the drugs
were excluded from the study.
A pro forma was designed to obtain basic demographic information
taking data of weight and height. Their body mass index (BMI) was
calculated using Quetelet’s index by formula weight/height2 and
expressed in kg/m2. Blood samples collected for estimation of FBS,
postprandial blood sugar (PPBS), glycosylated hemoglobin (HbA1c),
lipid profile, and OS markers. FBS and PPBS were estimated by
glucose oxidase method. HbA1c was calculated by cation exchange
high-performance liquid chromatography using D-10-Hemoglobin
Testing System (Bio-Rad). Lipid profiles were estimated using semi-
autoanalyzer, TRANSASIA, ERBA, and CHEM-5-PLUS. OS markers such
as malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO)
were measured using spectrophotometer.
Their baseline data and after 6 months supplementation data were
compared among both groups. Statistical analysis was performed using
Student’s paired t-test using SPSS software 20 version, and p<0.05 was
considered statistically significant.
As shown in Table 1, there is non-significant difference in age, weight,
and height of patients recruited in both groups, so they are matched
by all these factors. We recruited 17 females and 18 males in Group A
and 16 females and 19 males in Group B. Data are presented as mean ±
standard deviation from mean.
Table 2 shows sugar levels such as FBS, PPBS, and HbA1c values at
the initial stage of experiment. In the diabetic group, i.e., Group A has
significantly more levels in comparison to Group B, where normal
healthy controls were taken as control. As shown in Table 2, low-
density lipoprotein (LDL), very LDL (VLDL), triglyceride (TG), and
total cholesterol (TCh) levels were more and high-density lipoprotein
(HDL) is less in diabetic group, Group A than healthy group, Group B. OS
markers such as plasma GSH and NO levels are less and high MDA level
in Group A in comparison to Group B.
Effects of administration of ALA on different parameters are shown
in Table 3. It shows non-significant change of weight and BMI of both
groups due to ALA effect. Sugar levels such as FBS and PPBS show a
significant decrease after ALA supplement. HbA1c values show a
significant decrease in Group A but non-significant decrease in Group B
after ALA supplementation. Lipid profiles show a significant decrease
in both groups due to ALA. OS shows significant decrease as shown by
their markers in both groups due to ALA.
As shown in Table 1, all patients were matched by age and gender, also by
their height, weight, and BMI. The basal values of sugar levels show higher
values in Group A, who were diabetics. Due to worsening of hyperglycemia
condition overtime, progressive decrease in beta-cell function occurs [16].
This demands added medications such as insulin and other oral
hypoglycemic drugs to control this blood sugar level [17]. However, as
there is multifactorial pathogenesis to develop different complications in
T2DM, monotherapy appears insufficient to deal with T2DM [18,19].
ALA has antioxidant properties, can enhance glucose uptake in T2DM,
and also can prevent ß-cell destruction in T1DM [20-24]. Results from
this study indicate that oral ALA supplementation caused significant
reduction in plasma FBS and PPBS levels in both groups. HbA1c level was
significantly decreased in Group A, whereas a non-significant lowering
of HbA1c level was seen in Group B. These data are in agreement with
studies of Mazzone et al.,1984 [25];Packeret al.,2001[26]; Maritim
et al., 2003 [27]; and Kandeil et al., 2011 [28]. Glucose uptake is
increased due to ALA as it increases glucose transporter translocation
to cell membranes [29,30]. According to Sasvari and Nyakas, 2003 [31]
and Bitar et al., 2004 [32], ALA activates the pathway of insulin
signaling, causes phosphorylation of insulin receptors, and on myocytes
and adipocytes, it exerts insulin-like actions [28,33].
Lipid profile levels show increased LDL, VLDL, TGs, and TCh levels
in diabetic group, Group A in comparison to Group B. These results
supported by other studies such as Monnier et al.,1995 [34]; Abdel-
Azim et al., 2002 [35]; Mazzone et al.,1984[25]; Sheela and Augusti,
1992 [36]; and Sobenin et al., 1994 [37] studies. The abnormally
high concentration of serum lipid profiles in T2DM is mainly a result
of increased mobilization of free fatty acids from peripheral depots
as insulin inhibits hormone-sensitive lipase, while glucagon and
catecholamine enhance lipolysis [38,39].
Table 3 shows a significant lowering of LDL, VLDL, TG, and TCh levels
and significant increase in HDL, the good cholesterol level after ALA
treatment.ThesefindingsareinaccordancewithKocaket al.,2000[40];
Song et al.,2005[41];andLeeet al., 2005 [42]. Researchers reveal that
ALA activates catabolism of cholesterol into simpler components for
the eventual synthesis of steroid hormones [43].
As shown in Table 2, OS markers such as GSH and NO levels, which
combat the OS, are at lower level in Group A than Group B. Similarly,
MDA a product of lipid peroxidation is significantly more in Group A
than Group B. In patients with diabetes, there is increased production
of AGEs [28] and due to overgeneration of reactive oxygen species
(ROS), causing an imbalance and produces OS [44]. GSH is a tripeptide
present in all cells in micromolar concentrations has great antioxidative
property [45,46]. Low levels of GSH in T2DM patients in our study are in
accordance withfindings of other studies [47-51].
ß-oxidation of fatty acids initiated by increased activity of enzyme
fatty acyl coenzyme A oxidase due to hypoinsulinemia results
lipid peroxidation [52]. The products of lipid peroxidation such as
MDA are harmful to most of body cells and are associated different
disease conditions such as brain damage, micro- and macrovascular
complications [53].
ALA has amphiphilic nature and reduces ROS in cell membrane as
well as at their mitochondrial source level [53-56]. Inside cells and
tissues, ALA is reduced to dihydrolipoic acid that is even more potent
Table 1: Demographic data of both groups
Parameters Group A (n=35) Group B (n=35)
Age (years) 51.08±13.085 48.60±12.23
Weight (kg) 60.914±9.546 62.400±6.869
Height (cm) 158.685±6.430 159.514±6.045
BMI (kg/m²) 24.046±2.263 24.505±2.111
Table 2: Baseline sugar levels, lipid profile levels of both groups
Parameters Group A (n=35) Group B (n=35)
FBS (mg/dl) 161.31±15.94* 98.05±12.59*
PPBS (mg/dl) 211.37±22.30* 130.02±12.87*
HbA1c (%) 8.81±1.07* 5.26±0.42*
TCh (mg/dl) 223.34±25.77* 147.22±14.*83
TG (mg/dl) 175.57±29.83* 128.22±20.48*
HDL (mg/dl) 36.60±4.50* 39.34±3.21*
LDL (mg/dl) 161.85±19.60* 107.17±10.9*9
VLDL (mg/dl) 36.88±6.77* 28.80±4.22*
MDA (nm/ml) 1.967±0.581* 0.613±0.368*
GSH (µmol/L) 2.117±0.749* 2.631±0.495*
NO (µmol/L) 1.712±0.427* 2.139±0.536*
Asian J Pharm Clin Res, Vol 10, Issue 8, 2017, 204-207
Panda et al.
Our results show after ALA supplementation OS levels were reduced,
which support other studies [57-60].
Results obtained in our study indicate that the ALA can be used as an
antioxidant in T2DM treatment along with the antidiabetic therapy
to reduce different consequences as a result DM itself. ALA may be
used to manage OS and dyslipidemic conditions developed due to
hyperglycemic conditions in DM.
Dr. Pusparani Dash (Professor); and Dr Arati Mohanty (Professor)
from Department of Physiology; Dr. Sudhanshu S. Mishra (Professor
and HOD), Department of Pharmacology; IMS and SUM Hospital,
Bhubaneswar, for their kind support.
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Parameters Groups (n=35) Basal values Values after supplement
Weight (kg) Group A 60.914±9.546 61.085±9.262
Group B 62.400±6.869 62.428±6.431
BMI (kg/mt²) Group A 24.046±6.869 24.122±2.190
Group B 24.505±2.111 24.515±1.858
FBS (mg/dl) Group A 161.314±15.940* 122.428±16.705*
Group B 98.057±12.597* 90.657±10.389*
PPBS (mg/dl) Group A 211.371±22.305* 158.571±21.003*
Group B 130.028±12.871* 124.200±9.103*
HbA1c (%) Group A 8.817±1.073* 7.200±0.737*
Group B 5.262±0.422 5.242±0.398
LDL (mg/dl) Group A 152.685±25.986* 128.725±24.566*
Group B 82.240±14.506* 73.337±16.700*
HDL (mg/dl) Group A 36.600±4.506* 39.628±4.366*
Group B 39.342±3.217* 42.000±2.754*
VLDL (mg/dl) Group A 35.114±5.967* 32.617±5.577*
Group B 25.645±4.097 24.948±3.485
TG (mg/dl) Group A 175.571±29.836* 162.342±27.355*
Group B 128.228±20.488 124.742±17.426
TCh (mg/dl) Group A 223.342±25.772* 200.971±24.266*
Group B 147.228±14.830* 140.285±16.851*
MDA (nm/ml) Group A 1.967±0.581* 1.592±0.562*
Group B 0.613±0.368* 0.472±0.315*
GSH (µmol/L) Group A 2.117±0.749* 2.405±0.714*
Group B 2.631±0.495* 2.811±0.491*
NO (µmol/L) Group A 1.712±0.427* 1.990±0.426*
Group B 2.139±0.536* 2.318±0.522*
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... In different clinical trials, α-LA was used in 100-1,000 mg/day and these studies were placebo-controlled trials. The doses of 200-300 mg/day showed the best effects on diabetes compared to the placebo control by reducing blood glucose and insulin resistance (Ansar et al., 2011;Jacob, Streeper, et al., 1996;Panda, Panda, & Mishra, 2017;Udupa et al., 2013). According to different studies that were discussed above it seems that α-LA has a significant effect on the management of hyperglycemia. ...
... In various dyslipidemia animal models as lipid profile impairment, the α-LA treatment improved triglyceride levels (Jamor et al., 2018;Mythili et al., 2006;Panda et al., 2017;Pradhan et al., 2014), decreased LDL (Amom et al., 2008;Lukaszuk et al., 2009), increased HDL (Amudha et al., 2007;Carrier et al., 2014;Rideout et al., 2016;Thirunavukkarasu et al., 2004b;Uchendu et al., 2018), and reduced the total plasma cholesterol and free fatty acid (Jacob, Streeper, et al., 1996;E. Kim, Park, Choi, Kim, & Cho, 2008;Okanovic et al., 2015;Ozdogan et al., 2012). ...
Metabolic syndrome (MetS) is a multifactorial disease with medical conditions such as hypertension, diabetes, obesity, dyslipidemia, and insulin resistance. Alpha‐lipoic acid (α‐LA) possesses various pharmacological effects, including antidiabetic, antiobesity, hypotensive, and hypolipidemia actions. It exhibits reactive oxygen species scavenger properties against oxidation and age‐related inflammation and refines MetS components. Also, α‐LA activates the 5′ adenosine monophosphate‐activated protein kinase and inhibits the NFκb. It can decrease cholesterol biosynthesis, fatty acid β‐oxidation, and vascular stiffness. α‐LA decreases lipogenesis, cholesterol biosynthesis, low‐density lipoprotein and very low‐density lipoprotein levels, and atherosclerosis. Moreover, α‐LA increases insulin secretion, glucose transport, and insulin sensitivity. These changes occur via PI3K/Akt activation. On the other hand, α‐LA treats central obesity by increasing adiponectin levels and mitochondrial biogenesis and can reduce food intake mainly by SIRT1 stimulation. In this review, the most relevant articles have been discussed to determine the effects of α‐LA on different components of MetS with a special focus on different molecular mechanisms behind these effects. This review exhibits the potential properties of α‐LA in managing MetS; however, high‐quality studies are needed to confirm the clinical efficacy of α‐LA.
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Objective: To examine the dose-dependent influence of oral ALA supplementation on cardiometabolic risk factors in type 2 diabetes (T2D) patients. Design: We followed instructions outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations, Assessment, Development, and Evaluation Handbook to conduct our systematic review. The protocol of the study was registered in PROSPERO (CRD42021260587). Method: We searched PubMed, Scopus, and Web of Science to May 2021 for trials of oral ALA supplementation in adults with T2D. The primary outcomes were HbA1c, weight loss, and low-density lipoprotein cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride, C-reactive protein, and blood pressure. We conducted a random-effects dose-response meta-analysis to calculate the mean difference (MD) and 95%CI for each 500 mg/d oral ALA supplementation. Non-linear dose-response meta-analyses were also conducted. Results: We included 16 trials with 1035 patients. Each 500 mg/d increase in oral ALA supplementation significantly reduced HbA1c, body weight, CRP, FPG, and TG. Dose-response meta-analyses indicated a linear decrement in body weight at ALA supplementation of more than 600 mg/d (mean difference 600 mg/d: -0.30 kg, 95%CI: -0.04, -0.57). A relatively J-shaped effect was seen for HbA1c (mean difference: -0.32%, 95%CI: -0.45, -0.18). Levels of FPG and LDL decreased up to 600 mg/d ALA intake. The point estimates of the certainty of evidence were below minimal clinically important difference thresholds for all outcomes. Conclusion: Despite significant improvements, the effects of oral ALA supplementation on cardiometabolic risk factors in T2D patients were not clinically important.
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Meat and meat products have a high nutritional value. Besides major components, meat is rich in bioactive components, primarily taurine, l-carnitine, choline, alpha-lipoic acid, conjugated linoleic acid, glutathione, creatine, coenzyme Q10 and bioactive peptides. Many studies have reported their antioxidant and health-promoting properties connected with their lipid-lowering, antihypertensive, anti-inflammatory, immunomodulatory activity and protecting the organism against oxidative stress. The antioxidant activity of meat components results, among others, from the capability of scavenging reactive oxygen and nitrogen species, forming complexes with metal ions and protecting cells against damage. This review is focused to gather accurate information about meat components with antioxidant and biological activity.
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Objective: Two simple, accurate and reproducible spectrophotometric methods have been developed and validated for simultaneous estimation of metformin (MET) and pioglitazone (PIO) in bulk and tablet dosage forms. Methods: (1) Area under curve method (Area calculation): The proposed area under the curve method involves measurement of area at selected wavelength ranges. Two wavelength ranges were selected 228-238 nm and 265-275 nm for estimation of MET and PIO respectively. (2) Dual wavelength method: In the dual-wavelength method, two wavelengths were selected for each drug in a way so that the difference in absorbance is zero for another drug. PIO shows equal absorbance at 235 and 266 nm, where the difference in absorbance was measured for determination of MET. Similarly, the difference in absorbance at 216 and 241.5 nm was measured for determination of MET. Results: Linearity range for MET and PIO is 2-10 μg/ml and 10-50 μg/ml at respective selected wavelengths. Accuracy and precision studies were carried out, and results were satisfactory. The proposed methods have been validated as per ICH guidelines and successfully applied to the estimation of MET and PIO in their combined tablet dosage form. Conclusion: The developed methods are simple, precise, rugged and economical. The utility of the methods has been demonstrated by analysis of commercially available formulations.
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Solid lipid nanoparticles (SLNp) are a new class of alternative colloidal carriers developed at the beginning of the 1990s with the particle size ranging from 50 to 1000 nm. The SLNp consists of the drug molecule, surfactants, and solid lipid core suitable for incorporation of lipophilic, hydrophilic, and poorly water-soluble molecules. Diabetes mellitus (DM), is a prototype multifactorial complex diseases that regarded as one as one of the leading causes of morbidity and mortality in the world. DM caused by inadequate secretion of insulin or by the damaged cells of Islet of Langerhans of the pancreas. The present review provides information about the suitable choice of lipid, amount of surfactants was used for SLNp preparation, characterization, and various route of administration to increase the relative oral bioavailability in diabetic animals. Moreover, limitations associated with nanocarrier system for insulin delivery have also been discussed. Solid lipid Nanoparticulate system might be efficiently overcome peripheral hyper insulinemia, lipo-hyper-atrophy and improves the life quality of diabetic patients in the near future.
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Diabetes mellitus is a chronic metabolic disorder in the endocrine system and characterized by a varied and complex pathophysiology. World-wide there is a dramatic increase in the number of patients for type 2 diabetes, and hence it is becoming a serious threat to the health of mankind. Commercially a large number of drugs belonging to different classes such as biguanides, sulfonylureas, meglitinides and thiazolidinediones are available to control and treat the type 2 diabetic patients. However, none of these drugs are known to completely cure the diabetic phenotype. On the other hand, a long term usage of these drugs exhibits several side effects and complications to different organs of the body which ultimately lead to cardiovascular problems, liver disease, kidney disease and weight gain too. Like many other drugs, these anti-diabetic drugs are also known to interfere and interact with other non anti-diabetic drugs, if the patient is taking them for a long time. To combat the side effects of these drugs, complementary treatments may be found as a preventive measure and more promising in the management of disease phenotypes in these patients. As per reports available from a large number of studies, these complementary therapies may include physical exercise, dietary supplements and Nutraceuticals. © 2015, International Journal of Pharmacy and Pharmaceutical Science. All rights reserved.
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To evaluate the protective effects of α-lipoic acid on the kidneys of Goto-Kakisaki (GK) diabetic rats, ten GK diabetic rats were randomly divided into a diabetic control group and a lipoic acid-treated diabetic group with α-lipoic acid 35 mg·Kg-1 intraperitoneal injections. Four healthy Wistar rats served as normal controls. Malonaldehyde (MDA), ascorbic acid (vitamin C), vitamin E, glutathione (GSH) and superoxide dismutase (SOD) levels in renal homogenate, and urine protein excretion were measured. The expression of mRNA for NF-κB, NADPH oxidase subunits p22phox and p47phox in renal tissue was examined by realtime PCR. Pathological changes in renal tissue were evaluated by light and electron microscopy. There were significant increases in urine protein excretion, MDA levels and the expression of mRNA of NF-κB, p22phox and p47phox, and significant decreases in GSH, SOD, vitamin C and vitamin E levels in the diabetic control group compared with the normal control group. Pathological changes of renal tissue were more progressive in the diabetic control group than in the normal control group. All the parameters above were improved in the α-lipoic acid-treated diabetic group. Oxidative stress is increased in the kidney of type 2 diabetic GK rats. It is associated with the progression of diabetic nephropathy. α-lipoic acid can protect renal function in diabetic rats via its antioxidant activity.
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Purpose: The combined hyperglycemia lowering and antioxidant actions of α-lipoic acid (LA) contribute to its usefulness in preventing renal injury and other diabetic complications. The precise mechanisms by which LA alters diabetic oxidative renal injury are not known. We hypothesized that LA through its hypoglycemic effect lowers O-GlcNAcylation which influences the expression and activities of antioxidant enzymes which assume important roles in preventing diabetes-induced oxidative renal injury. Methods: An experimental model of diabetes was induced in rats by the administration of 40 mg/kg streptozotocin (STZ) intraperitoneally (i.p.) for five consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. Results: An improved glycemic status of LA-treated diabetic rats was accompanied by a significant suppression of oxidative stress and a reduction of oxidative damage of lipids, proteins and DNA. LA treatment normalized CuZn-superoxide dismutase (SOD) and catalase activities in renal tissue of diabetic rats. These changes were allied with upregulated gene expression and lower levels of O-GlcNA glycosylation. The accompanying increase in MnSOD activity was only linked with upregulated gene expression. The observed antioxidant enzyme gene regulation was accompanied by nuclear translocation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), enhanced expression of heat shock proteins (HSPs) and by reduction in O-GlcNAcylation of HSP90, HSP70, and extracellular regulated kinase and p38. Conclusion: α-Lipoic acid administration activates a coordinated cytoprotective response against diabetes-induced oxidative injury in kidney tissue through an O-GlcNAc-dependent mechanism.
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The stability and capacity of antioxidant status during chronic diabetes seriously influence the outcome of the long-term complications caused by oxidative stress. In the present study we investigated the effects of chronic streptozotocin-induced diabetes on the parameters of antioxidant status: activity of scavenging enzymes, gluthation-related and total antioxidant capacity, and degree of lipid peroxidation. Changes in the activities of superoxide-dismutase (SOD), glutathione peroxidase (GSH-Px), gluthatione reductase (GSH-R), and catalase, and in the content of reduced gluthation (GSH), and oxidised gluthatione (GSSG), and in the ratio of GSH/GSSG in blood samples were determined by means of biochemical methods. The degree of lipid peroxidation was measured via thiobarbituric acid assay (TBARS). Hyperglycaemia, ketosis and the accumulation of glycated proteins were estimated by measuring blood glucose, 3-OH-butirate, fructosamine and haemoglobin A 1C . In the course of chronic insulin-dependent diabetes, i.e. at 2 and 7 days, 10 weeks, and 6 and 8.5 months after streptozotocin injection, hyperglycaemia slightly while ketosis markedly attenuated. Lipid peroxidation was also attenuated. SOD activity decrease in the acute phase only. The activity of GSH-Px increased in the early phase while that of GSH-R mostly decreased in the chronic phase. GSH and GSSG concentrations moved into opposite direction in a time dependent manner. In conclusion, in chronic diabetes an attenuation of severity of diabetes was present throughout the post-injection period, which was well reflected in the improved antioxidant status and capacity.
Diabetic Nephropathy (DN) is the foremost reason of End Stage Renal Disease (ESRD) and a major cause of premature deaths amongst people with diabetes. It is one of the most common complications of diabetes mellitus (DM) and has majorly influenced patients’ morbidity and mortality. About 50% of patients suffering from DM for more than 20 years develop this complication. The present review focuses on the global scenario of diabetic nephropathy and different molecular mechanisms involved in its pathogenesis i. e. increased formation of advanced glycation end products (AGEs), enhanced glucose flux into polyol and hexosamine pathways, activation of protein kinase C (PKC) and other proinflammatory transcription factors. This review also highlights the precautionary measures to be taken by people with diabetes along with the therapeutic interventions involving angiotensin converting enzyme (ACE) inhibitors, renin inhibitors, angiotensin receptor antagonists, aldosterone antagonists, protein kinase C inhibitors, mechanistic target of rapamycin (m-TOR) inhibitors, agents inhibiting plasminogen activator inhibitor-1 (PAI-1), advanced glycation end products inhibitors, anti-inflammatory agents and antioxidant agents. © 2014, International Journal of Pharmacy and Pharmaceutical Sciences. All rights reserved.
The study was designed to find out the correlation between lipid peroxidation, lipoprotein levels to severity and complication of diabetes mellitus. Degree of lipid peroxidation was measured in terms of malondialdehyde (MDA) along with lipid profile and blood glucose in diabetes mellitus. It is categorised into insulin dependent diabetes mellitus (IDDM), non insulin dependent diabetes mellitus (NIDDM) and diabetes mellitus(DM) with complication. Total 112 known diabetic patients and 52 non-diabetic controls were studied. These patients were grouped as per the concentration of fasting blood glucose level i.e. controlled, poorly controlled, and uncontrolled group. There are significant increase in the lipid peroxide (MDA) and lipid profile except HDL cholesterol which is decreased, has been found in all groups as compared to controls In NIDDM group lipid peroxidation was markedly increased than IDDM group and it was higher in DM with complications. Other finding observed was that the level of lipid peroxide increased as per the increase in concentration of blood glucose. The increase lipid peroxidation in the hyperglycemic condition may be explained, as the superoxide dismutase enzyme which is antioxidant becomes inactive due the formation of superoxide radical within the cell. Maximum lipid peroxidation leads to the damage of the tissue and organs which results into complication in diabetic patients. High levels of total cholesterol appear due to increased cholesterol synthesis. The triglyceride levels changes according to the glycemic, control. The increase may be due to overproduction of VLDL-TG. It is concluded that good metabolic control of hyperglycemia will prevent in alteration in peroxidation and the lipid metabolism, which may help in good prognosis and preventing manifestation of vascular and secondary complication in diabetes mellitus.