condition found tbRes List
ALA, Alpha-Lipoic-Acid: Click to Expand ⟱
Features: antioxidant, energy production in cell mitochondria
Alpha-Lipoic-Acid: also known as lipoic acid or thioctic acid (reduced form is dihydrolipoic acid).
"Universal antioxidant" because it is both water- and fat-soluble and can neutralize free radicals.
-Treatment sometimes as ALA/N (alpha-lipoic acid/low-dose naltresone)
-Also done in IV
-Decreases ROS production, but also has pro-oxidant role.
Normal adult can take 300 milligrams twice a day with food, but they should always take a B-complex vitamin with it. Because B complex vitamins, especially thiamine, and biotin, and riboflavin, are depleted during this metabolic process.
α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
-It seems a paradox that LA functions as both antioxidant and prooxidant. LA functions the pro-oxidant only in special cancer cells, such as A549 and PC9 cells which should show high-level NRF2 expression and high glycolytic level. Through inhibiting PDK1 to further prohibit NRF2; LA functions as anticancer prooxidant.

α-lipoic acid possesses excellent silver chelating properties.

- ALA acts as pro-Oxidant only in cancer cells:#278 - Pro-Oxidant Dose margin >100uM:#304

- Bioavailability: 80-90%, but conversion to EPA/DHA is 5-10% (and takes longer time).
- AI (Adequate Intake): 1.1-1.6g/day.
- human studies have shown that ALA levels decline significantly with age
- 1g of ALA might achieve 500uM in the blood.
- ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
- Pilot studies or observational interventions have used flaxseed supplementation (rich in ALA) in doses providing roughly 3–4 g of ALA daily.
- Flaxseed oil is even more concentrated in ALA – typical 50–60% ALA by weight.
- single walnut may contain 300mg of ALA
- chia oil contains 55-65% ALA.
- α-LA can also be obtained from the diet through the consumption of dark green leafy vegetables and meats
- ALA is more stable in chia seeds, (2grams of ALA per tablespoon)
- ALA degrades when exposed to heat, light, and air. (prone to oxidation)

-Note half-life 1-2 hrs.
BioAv 30-40% from walnuts, 60-80% from supplements. Co-ingestion with fat improves absorption. Both fat and water soluble
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- small indication of inhibiting Cancer Stem Cells : CSC↓, CD24↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


RenoP, K,Renoprotection: Click to Expand ⟱
Source:
Type:
Protects kidneys
-Same as nephroprotective
Opposite is : Nephrotoxicity is toxicity in the kidneys
Scientific Papers found: Click to Expand⟱
3541- ALA,    Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology
- Review, Var, NA
*antiOx↑, α-LA has been widely used as an antioxidant compound in many multivitamin formulations, food supplements, anti-aging formulas, and even in human and pet food recipes
*IronCh↑, potential role in the chelation of metals and in restoring normal levels of intracellular glutathione (GSH) after depletion caused by toxicants,
*GSH↑,
*BBB?, ALA, which can pass through the blood-brain barrier (BBB
Apoptosis↑, increased level of apoptosis, mitochondrial membrane depolarization, ROS production, lipid peroxidation, poly-(ADP)-ribose polymerase 1 (PARP1), caspase 3 and 9 expression levels in simultaneous ALA (0.05 mM) and cisplatin(0.025 mM)-treated MCF7
MMP↓,
ROS↑,
lipid-P↑,
PARP1↑,
Casp3↑,
Casp9↑,
*NRF2↑, ALA's ability to activate Nfr2 in GSH production
*GSH↑,
*ROS↓, administration of ALA has been shown to reduce oxidative stress
RenoP↑, ALA also reduced lipid peroxidation in the kidneys caused by the anticancer drug cisplatin,
ChemoSen↑, ALA enhances the functions of various anticancer drugs such as 5-fluorouracil in CRC [146] and cisplatin in MCF-7 cells
*BG↓, ALA was shown to lower the blood glucose levels in patients with type 2 diabetes

3456- ALA,    Renal-Protective Roles of Lipoic Acid in Kidney Disease
- Review, NA, NA
*RenoP↑, We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled
*ROS↓, ALA’s renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death.
*antiOx↑,
*Inflam↓,
*Sepsis↓, figure 1
*IronCh↑, ALA can also chelate metals such as zinc, iron, and copper and regenerate endogenous antioxidants—such as glutathione—and exogenous vitamin antioxidants—such as vitamins C and E—with minimal side effects
*BUN↓, ALA can decrease acute kidney injury by lowering serum blood urea nitrogen, creatinine levels, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), thereby decreasing endothelin-1 vasoconstriction, neutrophil dif
*creat↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*MDA↓, pretreatment with ALA decreased MDA content and ameliorated renal oxidative stress
*NRF2↑, activate the Nrf2 signaling pathway, leading to upregulation of the second-phase cytoprotective proteins such as heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1)
*HO-1↑,
*NQO1↑,
*chemoP↑, ALA has also been shown to lower plasma creatinine levels and urine output, increase creatinine clearance and urine osmolality, and normalize sodium excretion in cisplatin kidney injury
*eff↑, ALA can also minimize renal toxicity induced by gold nanoparticles, which are often used as drug carriers
*NF-kB↓, Enhancing autophagy, inhibiting NF-KB, attenuating mitochondrial oxidative stress


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
Apoptosis↑,1,   Casp3↑,1,   Casp9↑,1,   ChemoSen↑,1,   lipid-P↑,1,   MMP↓,1,   PARP1↑,1,   RenoP↑,1,   ROS↑,1,  
Total Targets: 9

Results for Effect on Normal Cells:
antiOx↑,2,   BBB?,1,   BG↓,1,   BUN↓,1,   chemoP↑,1,   creat↓,1,   eff↑,1,   GSH↑,2,   HO-1↑,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   IronCh↑,2,   MDA↓,1,   NF-kB↓,1,   NQO1↑,1,   NRF2↑,2,   RenoP↑,1,   ROS↓,2,   Sepsis↓,1,   TNF-α↓,1,  
Total Targets: 21

Scientific Paper Hit Count for: RenoP, K,Renoprotection
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:29  Target#:1175  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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