Nežádoucí účinky a možná toxicita
Oxidative stress
- Laktoperoxidázový systém does not attack DNA and is not mutagenic
- Under certain conditions may contribute to oxidative stress
- May contribute to the initiation of breast cancer
- Ability to oxidize estrogenic hormones
- Producing free radical intermediates [6]
Breast cancer
- Oxidation of estradiol by lactoperoxidase
- Possible source of oxidative stress in breast cancer
- Ability of lactoperoxidase to propagate a chain reaction leading to
- Oxygen consumption
- Intracellular hydrogen peroxide accumulation
- Could explain the hydroxyl radical-induced DNA base lesions in female breast cancer tissue
- May be involved in breast carcinogenesis
- Ability to interact with estrogenic hormones
- Oxidise them through two one-electron reaction steps
- Reacts with the phenolic A-ring of estrogens
- Produce reactive free radicals
- May activate carcinogenic aromatic and heterocyclic amines
- Increase binding levels of activated products to DNA
- Suggests a potential role of lactoperoxidase-catalyzed activation of carcinogens in breast cancer [6]
Hydrogen peroxide (H2O2)
- From NAD(P)H oxidases (NOX) and dual oxidases (DUOX)
- Form HOSCN and hypohalous acids (HOX)
- That include hypochlorous acid (HOCl)
- Hypobromous acid (HOBr)
- hypothiocyanous acid (HOSCN)
- HOX readily reacts with amino groups to form haloamines (RNHX)
- Readily oxidizes cellular macromolecules
- Leading to toxicity
- SCN can
- Directly scavenge HOX
- Repair RNHX
- generate HOSCN
- Still has host defense properties
- Is better tolerated by host tissue than HOX [8]
HOSCN reacts selectively with sulfhydryl groups
- Resulting in the oxidation of proteins and thiol-based antioxidants [8]
Podobně jako rtuť ??
- Reaction of these sulfhydryl groups with HOSCN produces sulfenyl thiocyanates (RS-SCN) [8]
- May form
- Disulfides (RSSR)
- Sulfenic acids (RSOH)
- can then be repaired through enzymatic mechanisms [8]
HOSCN deplete antioxidants
- Such as glutathione (GSH) from cells
- Export from the cytosol
- protein conjugation of glutathione (PSSG)
- Rather than irreversible oxidation
HOSCN may also react with nucleophilic selenols
- Such as selenocysteine [8]
Selen soutěží o reakce s proteiny s rtutí... používá se ke snížení toxicity rtuti. Tedy asi není překvapení, že pokud něco reaguje podobně jako rtuť s SH- zbytky proteinů a snižuje hladinu glutathionu podobně jako rtuť, že se to nějak dotkne i selenfilních molekul
- Some capacity of HOSCN to react with nitrogen atoms resulting in
- Thiocyanatimines
- Thiocyanatosulfonamides
- Formation of thiocyanogen (SCN2)
- From the condensation of HOSCN by SCN
- May be rapid hydrolysis of SCN2 in physiologic matrices
- SCN-catalyzed decomposition of HOSCN
- Consistent with the formation of SCN2 [8]
Mikrobiální rezistence k HOSCN
- Kmeny streptokoků - Str. salivarius
- NADH-hypothiocyanite oxidoreductase that reduces OSCN- back to SCN
