Traumatic brain injury (TBI) induces direct mechanical injury and secondary injury processes, among which ferroptosis, a regulated and iron-dependent form of cell death, has emerged as a key mechanism. Circadian clock disruption is also commonly described in TBI, especially mild TBI (mTBI) patients, and is reported to exacerbate pathological outcomes of TBI. However, the crosstalk between circadian clock dysfunction and ferroptosis in mTBI remains unclear. Using a mouse mTBI model, disrupted expression of core circadian clock regulators BMAL1, CLOCK, and PER2 was observed, accompanied by iron accumulation, blood-brain barrier (BBB) leakage, and neuronal damage. Ferroptosis inhibitors, melatonin (MLT) and liproxstatin-1 (Lip-1), alleviated mTBI-induced weight loss and neurological dysfunction. In contrast to MLT, Lip-1 failed to rescue body temperature rhythmicity, although both agents modulated circadian clock at the molecular level. Mechanistically, the Bmal1 downregulation sensitized HT-22 neurons to RSL3-induced ferroptosis in vitro by exacerbating oxidative stress and iron overload. Collectively, these findings demonstrated an asymmetric crosstalk, in which circadian clock disruption promotes ferroptosis, and inhibition of ferroptosis feeds back to modulate clock gene expression without restoring behavioral rhythms. This circadian–ferroptosis axis may represent a novel and promising target for therapeutic intervention in post-TBI neuroprotection.
Sorry, I should have pointed it out… it showed that Maypro Industries is a key distributor of micro melatonin… I’d contact them and ask if they know where you can buy it, or if they sell to individuals (I doubt it but if you don’t ask, you don’t get
Sodium sulfite (SS) is a common food additive that is widely absorbed and distributed throughout the body, but its excessive intake has been linked to adverse health effects. Here, we investigate the impact of chronic SS exposure on bone tissue and the underlying mechanisms. Using a mouse model, we demonstrate that prolonged SS exposure induces significant bone loss, which correlates with alterations in ferroptosis-related markers. In vitro, SS exposure activates ferroptosis, which is characterized by elevated reactive oxygen species levels and impaired osteogenic differentiation in MC3T3 cells. Notably, melatonin, a potent endogenous antioxidant, mitigates SS-induced oxidative stress, inhibits ferroptosis, restores osteoblast function, and alleviates bone loss in mice. These findings highlight ferroptosis as a critical contributor to SS-induced osteoporosis and identify melatonin as a promising therapeutic agent for its prevention and treatment.
O3: “what effect does sodium sulphite have on mitochondria”
Bottom line: sodium sulfite undermines mitochondrial energy production by blocking electron flow, collapsing the proton gradient, opening the permeability-transition pore and promoting ROS formation. Organisms cope by oxidising it to sulfate, but when that capacity is exceeded—or genetically absent—mitochondrial failure and cell death follow.
Hence the question arises “is it ferroptosis specifically or just protecting mitochondria more generally”.
I would guess the latter, but am too busy to look at the paper to see if I am right or not.
