Methylene blue (MB), an alternative electron carrier, rescues hepatocytes from EFV/INH-induced lethal injury

[Candeias]

Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes


"If the mechanisms of EFV/INH-induced hepatocyte demise indeed involved a joint inhibitory effect on complexes I and II, then circumvention of this proximal ETC block with an alternative electron carrier that feeds electrons into the ETC at a more distal site should protect against cell injury. One of these alternative electron carriers is methylene blue (MB), a redox-active agent that has been shown to directly accept electrons from NADH and reduce cytochrome c without the involvement of ubiquinone. We found that, in the presence of mitochondria and EFV (30 μM), MB greatly enhanced the consumption of NADH in a concentration-dependent manner, even exceeding the rate caused by normal complex I activity by several-fold. This confirms the ability of MB to oxidize NADH even under conditions of chemical inhibition of complex I. Next, we investigated whether MB was able to protect cultured hepatocytes against cell injury induced by exposure to combined INH (1000 μM)/EFV (30 μM). We found that MB (>30 μM) protected against the opening of the mPT pore and the subsequent hepatocellular necrosis, as demonstrated by the retention of calcein in the mitochondrial matrix in the presence of otherwise cytotoxic concentrations of EFV/INH . Furthermore, MB was able to almost completely prevent LDH release and loss of intracellular ATP. Control experiments confirmed that MB did not interfere with the LDH assay itself (data not shown). Taken together, these data strongly suggest that the toxicity caused by EFV/INH co-exposure is the consequence of a severe inhibition of ETC function, resulting in peroxynitrite stress, and that this impaired pathway can be bypassed by MB, resulting in full protection against cell injury."



The dose is apparently high, so there are no worries in a few tens of milligrams of MB, but I notice a difference in my behavior/attitude (serotogenic) when supplementing at "higher" doses ~>50 mg.

 

[L_C]

I found MB quite an interesting substance. I feel like it helps greatly with estrogen symptoms in the second half of my cycle and pairs greatly with progesterone.

 

[Valor]

I found MB quite an interesting substance. I feel like it helps greatly with estrogen symptoms in the second half of my cycle and pairs greatly with progesterone.

I had no idea it worked well for that... thank you I will look into it.

 

[Candeias]

Targeting mitochondria with methylene blue protects mice against acetaminophen-induced liver injury

"Based on these findings, we hypothesized that methylene blue (MB), a mitochondria-permeant redox-active compound that can act as an alternative electron carrier, protects against APAP-induced hepatocyte injury. We found that MB (<3 µM) readily accepted electrons from NAPQI-altered, succinate-energized complex II and transferred them to cytochrome c, restoring ATP biosynthesis rates. In cultured mouse hepatocytes, MB prevented the mitochondrial permeability transition and loss of intracellular ATP without interfering with APAP bioactivation.
(...)
Conclusion: MB can effectively protect mice against APAP-induced liver injury by bypassing the NAPQI-altered mitochondrial complex II, thus alleviating the cellular energy crisis. Because MB is a clinically used drug, its potential application after APAP overdose in patients should be further explored."

 

[Donna57]

I was put in touch with a lab in Germany IGL that did a blood serum test for the Mitochondria and found that my SOD1 enzyme is blocked (attached) I'm not sure how to understand this but thought maybe sharing on this site of knowledgeable and intelligent individuals someone will lead me down a path to explore. I started drinking MB Low dose to help with the electron transfer.

I'm now wondering if my higher than average blood sugar levels are due to not processing glucose properly. Im 5"5 125lbs my daily food take is 2 meals I have always internement fasted as a lifestyle and exercise so there was no apparent reason for the recent high blood sugar ( last 6 months)

 

[youngsinatra]

Have you measured your serum copper/ceruloplasmin?

 

[Donna57]

@youngsinatra My copper levels are fine based on my metabolic panel in October. Are you thinking my body is not processing copper? My labs attached. I appreciate your time, knowledge and feedback.