physionic covers a ot (eg inflammation), and even michael gregor used to cover a lot of those (though some of the studies he cites may be sus - eg studies about blueberries attenuating the oxidative insults after high glycemic meals).
Um 8oxoG, cfDNA, methods of lipid peroxides, some iollo stuff, some proteomics of sleep deprivation stuff
i thought Nfl but it’s a months long readout so not as much
also IL6 maybe.
some people have basically no CRP so CRP is not the best measure
- Isoprostanes are themselves PUFA-indexed. F2-IsoPs from AA (n-6), F3-IsoPs from EPA (n-3), and — the one to flag for your whole thread — F4-neuroprostanes from DHA (C22:6 n-3). DHA is concentrated in neuronal membranes, so F4-NeuroPs are about as close to a brain-specific lipid-peroxidation readout as blood gives you. That’s a far better “did the flight oxidize my neural lipids” candidate than generic F2-IsoP. Their reactive cousins, isoketals/isolevuglandins (γ-ketoaldehydes), adduct proteins so fast they mostly exist as adducts.
- Hydroperoxides → hydroxy-acids: HpETEs→HETEs (from AA), HODEs (from linoleic acid, C18:2 n-6). HODEs are plausibly the most abundant oxidized-lipid species in human plasma, because LA is the most abundant PUFA — so they beat isoprostanes on sensitivity even if they lose on specificity.
- Reactive aldehydes / the ALE precursors: you’re reaching for 4-HNE I think (not 9-), the canonical n-6 product, plus its n-3 twin 4-HHE, plus MDA, acrolein, ONE. These are the electrophiles that Michael-add onto Cys/His/Lys and onto phosphatidylethanolamine → advanced lipoxidation end-products.
- Oxidized phospholipids (OxPLs; oxidized cardiolipin is mitochondria-specific) — which loops straight back to your earlier membrane-integrity point.
- The adductome: ALEs are the lipid parallel to AGEs (glycation), with carboxymethyl-lysine sitting at the overlap of both.
First, a framing correction that matters: these aren’t three flavors of the same thing. Acrolein and •OH are oxidative, but MGO is a category slip — it’s a dicarbonyl/glycative stressor, spun off mostly from triosephosphates during glycolysis (and secondarily lipid peroxidation), detoxed by the GSH-dependent glyoxalase system. So its footprint tracks glucose/fructose flux and GSH capacity, not ROS per se. The unifying trap across all three: every one of these markers is a ratio of production flux to detox capacity, which is where the interpretation lands you in trouble. (I’m assuming “HO” = hydroxyl radical; flag me if you meant heme oxygenase.)
MGO / MG (methylglyoxal). Three readout layers:
- Direct/flux: MGO itself (LC-MS/MS after o-phenylenediamine derivatization → 2-methylquinoxaline), plus the glyoxalase-flux markers — D-lactate as the detox end-product and S-D-lactoylglutathione as the intermediate; GLO1 activity/expression itself. Glo1 and Glo2 with reduced glutathione detoxify MGO to lactate.
- Adducts (the AGE footprint): MG-H1 is the one to measure — glycation directed to arginine guanidino groups forming mainly the hydroimidazolone MG-H1, quantified by stable-isotope-dilution tandem MS and by specific monoclonal antibodies, with free MG-H1 released by proteolysis for excretion (so urinary MG-H1 is a systemic readout). Then CEL (carboxyethyl-lysine) and MOLD from MGO; CML and GOLD from glyoxal; 3-deoxyglucosone gives 3DG-H, plus fluorescent argpyrimidine. I’m fairly confident MG-H1 is quantitatively dominant. One dataset had CML, CEL, and MG-H1 each significantly predicting fast progression of diabetic nephropathy, where HbA1c at the same timepoint did not — single dataset, don’t over-weight, but it’s the “adducts beat the glucose average” flavor you’d expect.
Acrolein. Maximally promiscuous source (lipid peroxidation + polyamine oxidation via SMOX/PAO + myeloperoxidase on threonine + environment: smoke, fried food, exhaust — that last bundle ties straight to your airport/travel thread). Readouts:
- Urine flux: 3-HPMA (3-hydroxypropylmercapturic acid), the GSH-mercapturate — the major urinary acrolein metabolite, LC-APCI-MS/MS with a ¹³C₃ internal standard, dropping ~78% after four weeks of smoking cessation, elimination t½ ~10 h.
- Protein adducts (plasma/tissue): PC-Acro — FDP-Lys (Nε-(3-formyl-3,4-dehydropiperidino)lysine) and MP-Lys (Nε-(3-methylpyridinium)lysine), increased in pathological lesions and plasma across diseases.
- DNA adducts: Acr-dG — α- and γ-hydroxy-1,N²-cyclic-propano-deoxyguanosine, in buccal cells; γ-OH is the predominant isomer in leukocyte DNA.
- The sharp trap (this is the good one): the mercapturate and the protein adduct can move in opposite directions. In stroke, plasma acrolein-protein adduct rose while urinary 3-HPMA fell — attributed to GSH depletion at the lesion, so less conjugate forms and unmetabolized acrolein hits proteins instead. So a low 3-HPMA can mean low exposure or exhausted GSH with high damage. You need adduct + mercapturate + the GSH pool read together, or you’ll invert the story.
Hydroxyl radical (•OH). The problem child: diffusion-limited-reactive with everything, effectively unmeasurable directly, so you only ever read stable footprints — and the popular one is the least clean.
- DNA: 8-oxo-dG is the workhorse but notoriously prone to spurious oxidation during DNA extraction, so absolute values are contested. 8-OHGuo is the RNA-oxidation analogue, urinary, and correlates with 8-OHdG, with less diurnal drift in non-smokers. The connoisseur’s pick is 8,5′-cyclopurine-2′-deoxynucleosides (cdA/cdG): they don’t suffer oxidative artifacts during work-up like 8-oxo-dG, and their glycosidic-bond resistance plus oxygen stability make them a robust biomarker of hydroxyl-radical DNA damage, and they’re NER-only repair (so they accumulate). Fairly confident these are the cleanest DNA readout.
- Protein: o-tyrosine as a stable marker of phenylalanine oxidation by hydroxyl radical, versus 3-nitrotyrosine as the reactive-nitrogen marker — para-Tyr being the enzymatic product, so ortho- and meta-tyrosine are the non-enzymatic •OH fingerprints; plus o,o′-dityrosine crosslinks. Protein carbonyls are the generic, non-specific catch-all.
- Lipid: •OH initiates the whole peroxidation cascade, so the isoprostanes/HODEs/aldehydes from before are partly •OH readouts one step downstream.
- Scavenger footprints (fairly sure, from training not the searches): allantoin — humans lack uricase, so allantoin is non-enzymatic urate oxidation, and the allantoin:urate ratio is a systemic oxidative-stress index; and the salicylate/aspirin trap → 2,3-DHBA, a fairly •OH-specific probe used in microdialysis.
If forced to rank •OH readouts by robustness (genuine uncertainty in the ordering, ~plausible): cyclopurines (•OH-obligate, artifact-free) > o-/m-tyrosine or salicylate-2,3-DHBA > allantoin:urate > 8-oxo-dG (most used, most artifact-prone). I wouldn’t die on the exact sequence.
One speculative tie-in to your flight thread I like: higher O₂ inhibits cyclopurine formation by reacting with the C5′ radical before cyclization — so hypoxia favors cyclopurines and tilts the •OH DNA-damage spectrum away from 8-oxo-dG. Under mild cabin hypoxia the signature could shift accordingly. I’m speculating on the flight application; the O₂-competition chemistry itself is solid.
Accessibility coda, since it’s the running wall: almost none of these are on iollo/theriome/Metabolon. An untargeted Metabolon-class run might catch MGO, D-lactate, some free AGEs, and the thiol redox couples; urinary 8-OHdG and 8-isoprostane have semi-consumer ELISAs (unreliable versus LC-MS/MS). MG-H1, CEL, 3-HPMA, FDP-Lys, cyclopurines, o-/m-tyrosine are all research-grade targeted MS. So the specific damage footprints you’re asking after are, with two shaky exceptions, not off-the-shelf — same gap as before: easy to perturb, hard to catch.