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c60/DMSO solution Wistar Rat HD model reverses symptoms and prevents mito-dysfunction

c60 dmso huntingtons glutathione system 3-npa mnsod oxidative stress mitochondrial dysfunction nrf2 / are

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#1 ambivalent

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Posted 30 November 2022 - 05:18 PM


"C60 fullerene as a potent free radical scavenger and antioxidant could be a beneficial means for neurodegenerative disease prevention or cure."

 

https://www.ncbi.nlm...les/PMC8196695/

 

A small study over a short time frame, but quite remarkable. It pretty obviously needed a DMSO control group too. But some impressive homeostatic behaviour and may explain why c60oo effects wear off in time as it perhaps "corrects imbalances". Very little difference between controls and c60/DMSO groups though age of rats not indicated. 

 

A lot of concerns over DMSO and possible apoptopic effects are at least assauged here when in solution with C60. It would be nice to see some longer safety and even life-span studies.

 

"Our results indicated that C60 can prevent 3-NPA-induced mitochondrial dysfunction through the restoring of mitochondrial complexes’ enzyme activity, ROS scavenging, modulating of pro/antioxidant balance and GSH/GSSG ratio, as well as inhibition of mitochondria-dependent apoptosis through the limitation of p53 mitochondrial translocation and increase in Bcl-2 protein expression. C60 improved mitochondrial protection by strengthening the endogenous glutathione system via glutathione biosynthesis by up-regulating Nrf2 nuclear accumulation as well as GCLC and GSTP protein level."

 

 

"Our results revealed that C60 prevented mitochondrial oxidative stress and mitochondrial dysfunction induced by a high dose of 3-NPA administration in rats. Beneficial effects of C60 were achieved, at least in part, by the elimination of ROS overproduction with the consequent decrease in LPO intensity as well as by the reduction of impairment of respiratory chain enzymes, especially SDH. Moreover, C60 modulated the pro/antioxidant balance and GSH/GSSG ratio in mitochondria. In addition to its strong antioxidant properties, C60 application inhibited the mitochondria-dependent apoptosis through the termination of p53 accumulation in mitochondria and the rise of Bcl-2 protein expression. Based on our studies, it could be concluded that the above effects and the degree of their manifestation depended on tissue specificity and C60 treatment regime. In brain mitochondria, C60 applied in the pre-treatment mode caused a significant decrease in oxidative stress markers and strengthening of the antioxidant capacity in comparison to the post-treatment regimen. It is possible to conclude that C60 preventive application was more effective than C60 injection after the oxidative intervention. At the same time, in skeletal muscle mitochondria, the intensification in antioxidant capacity was registered for the post-treatment regimen of C60 administration."

 

 

"Similar changes in nuclear Nrf2 protein content and its targeted GSH-related enzymes permit us to suppose that under 3-NPA intoxication, along with other mechanisms, Nrf2/ARE-antioxidant pathway may be involved in the regulation of GSH homeostasis. Since exogenous injection of GSH is not effective, the modulation of glutathione biosynthesis by C60 could be an excellent therapeutic tool for the prevention or cure of neurodegenerative disorders caused by oxidative stress. However, further studies in relevant models would be necessary to provide new insights into the intrinsic molecular mechanisms of C60 protective effects."

 

"The present study demonstrated that C60 administration evoked further enhancement of nuclear Nrf2 protein in the brain and skeletal muscle of rats incurred by 3-NPA with an associated decrease in the cytosol fraction. The levels of protein expression of GSH-related enzymes correlated positively with Nrf2 nuclear protein level, supposing that the upregulation of GCLC and GSTP can depend on the Nrf2/ARE pathway. We have assumed that C60 influenced GSH recycle via the induction of γ-GCLC and GSTP protein expressions and this is necessary for the recovery of GSH system homeostasis.

Therefore, C60 treatment led to significantly increased levels/activities of MnSOD, GSH, and GST in the mitochondrial fraction. We supposed that the increased synthesis of GSH as well as MnSOD and GSH-related enzymes in the cytoplasm could simultaneously increase the level of these antioxidants in the mitochondrial compartment. Since mitochondria are crucial intracellular targets for oxidant cell damage [11], our findings are important for understanding the phenomena of C60 action leading to cyto- and mitoprotection against 3-NPA-induced oxidative stress in the brain and muscle cells.

 

DMSO c60 solution preparation:

 

"A stable colloid solution of fullerene C60 in dimethyl sulfide (DMSO) was prepared as previously described in Maznychenko et al. [62]. Briefly, DMSO (purity > 99.99%, Sigma-Aldrich, Germany) was added to the pure fullerene C60 powder (Sigma-Aldrich, Germany, purity > 99.99%) at a final concentration of 1 mg/mL. Further, the mixture was treated in an ultrasonic bath for approximately 35–45 min. The procedure was continued until a visible, brown-colored solution was obtained. In order to monitor the quality of the fullerene C60-DMSO solution, UV-vis spectrophotometry, followed by atomic force microscopy (AFM) was used. Registered absorbance spectra, as well as measured sizes of the dispersed fullerene C60 nanoparticles, were consistent with the previously reported data"

 

"The controls/vehicles were administrated i.p. with an equal volume of DMSO solution dissolved in distilled water once a day along the same period. Note that in all cases, the final DMSO concentration in the injected solutions was not more than 1%."

 

 

 

 


Edited by ambivalent, 30 November 2022 - 05:47 PM.

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Also tagged with one or more of these keywords: c60, dmso, huntingtons, glutathione system, 3-npa, mnsod, oxidative stress, mitochondrial dysfunction, nrf2 / are

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