antioxidants

1. Dr. Nishtha Jain
Senior Resident
Department of Neurology
GMC, Kota.

2.  All aerobic organisms are susceptible to oxidative
distress as semireduced oxygen species are produced by
mitochondria during respiration.
 The exact amount of ROS produced is 2% of the total
oxygen consumed during respiration.

3.  Free radical or oxidative injury may be a fundamental
mechanism underlying a number of human neurologic
diseases.
 Antioxidants are endogenous or exogenous compounds
that either reduce the formation of free radicals or react
with and neutralize them, thus potentially protecting the
cell from oxidative injury.

8. Neurological conditions
 Alzheimer Disease
 Parkinsons Disease
 Huntingtons Disease
 Freidrich Ataxia
 Mitochondrial Diseases
 Stroke
 Trauma

9. Vitamin E
 Vitamin E is regarded as the prototypic antioxidant
vitamin.
 the one most extensively studied in neurology,
particularly in the area of chronic neurodegenerative
disease.

13. Treatment with vitamin E at 2000 IU/d had no
effect in delaying need for levodopa therapy in
patients who were followed up over a mean
period of 14 months.

16. CLINICAL TRIALS WITH TIRILAZAD
 Tirilazad mesylate, a 21-aminosteroid that inhibits lipid
peroxidation, has been studied in 4 acute neurologic
disorders, with mixed results.

21. Ebselen
 Seleno-organic compound.
 Act through glutathione peroxidase like reaction.
 Shown efficacy in stroke.

24. Co-enzyme Q10
 small lipophilic molecule present within the inner
mitochondrial membrane in association with the ETC
complexes, which transfer electrons between complexes
I and II to complex III resulting in the ultimate production
of ATP.
 Because of its ability at undergoing redox reactions,
coenzyme Q10 acts as a potent antioxidant preventing
oxidation of proteins, lipids, lipoproteins & DNA.

25.  also contributes in preventing the opening of the
mitochondrial membrane transition pore which permits
passage of enzymes and other molecules which can
contribute to the depolarization of the mitochondrial
membrane potential, apoptotic events and DNA
fragmentation.
 also have anti-inflammatory and anti-atherosclerotic
properties.

27.  In the cells pre-treated with CoQ10 prior to H2O2
treatment, mitochondrial ROS generation was
significantly lower in comparison to mitochondria isolated
from cells that had not been pre-treated.
 Further, it was observed that the mitochondrial
membrane potential was maintained in the presence of
CoQ10.

31.  Idebenone, a benzoquinone derivative, is structurally
related to coenzyme Q, an intermediate in the oxidative
phosphorylation pathway.
 Idebenone inhibits lipid peroxidation through free radical
scavenger activity and appears to act as an antioxidant.

32.  It protects against glutamate-induced neurotoxicity and -
amyloid-induced cytotoxicity in hippocampal cell
culture,and it increases levels of nerve growth factor in
brain.
 Second, idebenone also modifies neurotransmitter
function, increasing serotonin and norepinephrine
turnover in neuronal cell cultures.
 Finally, it improves learning and memory in a variety of
models including brain ischemia and basal forebrain
lesion.

40. ALS
 One of the proposed mechanisms of neuronal death in
ALS is free radical accumulation resulting from oxidative
stress.
 This increase might result from altered mitochondrial
energy metabolism related to age, environmental factors
leading to increased free radical production, or glutamate
mediated excitotoxicity.

41. Commonly considered antioxidant medications in ALS
include:
 Vitamin C (ascorbic acid)
 Vitamin E (a-tocopherol)
 L-deprenyl (selegiline)
 N-acetylcysteine
 Dehydroepiandrosterone
 Combination antioxidant therapy

42. Mitochondrial diseases

46. Name of
compound
Trade name Cost
Idebenone norwayz 138
Cocktail Regimes 240-360
Vitamin E Evion 20
Melatonin Meloset 30
L-carnitine carnisure 180

47. Conclusion
 No definite evidence.
 Limited knowledge regarding dosing schedules.
 Cocktail regimes not cost effective.

48. Thank you

49. Referrences
 Antioxidant Therapy in Neurologic Disease.Norman
Delanty et al. Arch Neurol. 2000;57:1265-1270.
 Antioxidants in Huntington's disease.A Johri et al.
Biochimica et Biophysica Acta. 1822 (2012) 664–674.
 Oxidative Stress and the Use of Antioxidants in Stroke .
R Shirley et al. Antioxidants 2014, 3.
 A Modern Approach to the Treatment of Mitochondrial
Disease. Parikh S et al. Current Treatment Options in
Neurology 2009, 11:414–430.
 Coenzyme Q10 and Neurological Diseases.
Michelangelo M et al. Pharmaceuticals 2009, 2.