Vitamin e Methotrexate

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Introduction

● Antioxidant during fat oxidation protects


Vitamin E:
membranes from reactive oxygen species
Fat-soluble compound
(ROS)
found in cell
membranes ● Inhibit platelet aggregation (by affecting
enzymes & adhesion molecules)
● Preventive benefits: cardiovascular
disease, cancer, cataracts, Alzheimer's

8 Forms: ● Deficiencies are rare & symptoms include:


Alpha, Beta, Gamma, & ○ Muscle weakness
Delta tocopherols and ○ Coordination and walking difficulties
tocotrienols ○ Vision deterioration
Sources
Our body absorbs the alpha-tocopherol form of
Vitamin E from both food and supplements

● RDA: 4-15 mg/day (increases with age)


● Foods
○ Dark leafy greens (½ cup = 1-2 mg)
○ Vegetable Oils (1 Tbs = 1-6 mg)
○ Nuts (1 oz = 4-7 mg)
○ Seeds (1 oz = 7 mg)
● Supplements
○ Digestive problems
○ Cystic Fibrosis
Absorption
● Fat soluble vitamin → absorbed best with other lipids
● Vitamin E activates gene expression via PXR (Pregnane X Receptor)
and RXR (retinoid X receptor)
○ PXR is critical in xenobiotic metabolism
○ Regulate genes that aid in hepatic detoxification,
oxidation, and conjugation

Ingestion
VLDLs

Chylomicrons Fat storage in


Liver adipose tissue
Small Intestine
Respiratory System
● Works as an antioxidant in the lung
○ Protects against free radicals → lead to oxidative stress
● Correlation of Vitamin E and causes of childhood asthma
[Meta-Analysis (2000-2016)]
○ Conclusion: mom’s increased Vitamin E supplementation
decreased childhood asthmatic diseases
● Deficiency can cause reversible changes
○ Hyperoxia
○ Signs of apoptosis
○ Reduces lipid synthesis for alveolar cells
■ Reduces protection for liver cells
Immune System
● Vitamin E slows age-related decline
● Lymphocyte populations - proliferation
● Effects on Immune System:
○ Increased antibody response to vaccinations
○ Increase of plasma Vitamin E levels
○ Increase in DTH response (inflammatory response)
○ Reduced levels of plasma lipid radicals
○ Improves T-cell mediated functions
○ Increased Leukocyte phagocytic capacity
Excretory System
New findings show Vitamin E may help with urinary tract infections (UTI)

-Milder symptoms when paired with an antibiotic

Taking extra vitamin E may not have any advantage

Vitamin E is not eliminated by the urinary system


Reproductive System
Male Female
Protect sperm from ROS damage Vitamin E -> prostaglandins ->
prolactin -> physical and
Supplementation is effective in emotional symptoms of
reducing the number of sperm premenstrual syndrome (PMS)
affected by ROS and improving
motility Pregnancy
- Your body will demand
higher levels due to an
increase in blood volume
Nervous System
Oral supplement:
- α-Tocopherol
- 300mg/day
- Reaches the cerebrospinal fluid and brain
Function:
- Delays neurological disorders
- Antioxidant
● Protects against peroxidation of plasma membrane lipids
- Protects central nervous system: the cerebellum.
● Tocopherol + protein and albumin concentration increases in CSF
→ protects the brain
● Transportation linked with plasma proteins
- Prevent oxidative damage & motor coordination deficits & cell loss
Endocrine System
● Vitamin E can help in balancing hormones
○ Ease symptoms of menopause
○ Can help balance progesterone levels
■ Progesterone is suppressed by contraceptives
■ Plays an important role in the menstrual cycle and
maintaining the early stages of pregnancy
Methotrexate
➢ Antimetabolite (interfere
with DNA & RNA growth)
➢ Antineoplastic (used to
kill rapidly growing cells)

Rapidly dividing cells most


susceptible (immune cells,
hair matrix, fetal cells, GI
lining)
Methotrexate
Can be taken orally or by subcutaneous or intramuscular injection
(Always by prescription only)

Dosages vary depending on treatment & body size


● Oral: 5-50 mg (frequency also varies)
● Injection: 7.5-25 mg/week

Absorption is dose dependent (23%-95%)


● Oral bioavailability averages 60% at lower
dosage
● Injection is completely absorbed
Methotrexate Common side effects
● Suppressed immune
Hydrophilic system
● Temporary hair loss
Cannot be taken during conception, ● Loss of appetite
pregnancy, or breastfeeding ● Bloody urine, stool, vomit
Lots of potential drug interactions ● Mouth sores
(115+), but often prescribed multiple ● Stomach upset/ diarrhea
drugs ● Signs of anemia
● Joint pain
● Dark urine/ black stool
● Teratogenicity
● Potential infertility
Methotrexate & Cancer
● Commonly used for lung, head & neck, breast, blood, bone, lymph
node, and uterine cancers
● Blocks an enzyme needed for cell survival
● Dosage varies from 5-50 mg per day or per week, typically with rest
period
● Often just part of treatment plan
Methotrexate & Rheumatoid Arthritis
● One of the most effective and
common RA treatments
○ Reduces necessity of B-lymphocytes
corticosteroids Recognize antigens
● Unclear anti-rheumatic mechanism and produce
specialized
○ Inhibits granulocyte activity and
antibodies
depresses B-lymphocytes (Example: vaccines)
○ Reduces concentration of IgA
and IgM rheumatoid factors
Methotrexate & Psoriasis & Psoriatic Arthritis
● Immune system attacks healthy body tissues
○ Overproduction of skin cells
○ Inflammation
● Psoriasis
○ Suppresses inflammation & skin cell production
○ Systemic treatment for severe psoriasis
● Psoriatic Arthritis
○ Disease-modifying antirheumatic drug
○ Slow progression to preserve joints and tissues
Methotrexate & Crohn’s Disease
● Works as an immunosuppressant
○ Reduces and controls bowel inflammation
● Treatment for chronically active and remissive Crohn’s disease
○ Reduces need for prednisone (corticosteroid)
○ Can rapidly improve symptoms (~6 weeks)
● Minimum effective dose uncertain
○ Recommended 25 mg/week and 15 mg/week based on goal
○ Daily dose increases toxicity risk

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