In Growing older, researchers have printed negative results on the long-term use of methylene blue and mitoquinone (MitoQ), two popular antioxidants, to sustain bone health in mice.
Oxidative stress and bone well being
Earlier work has discovered that oxidative stress, which is often related to age-related illness and harm, is said to bone illnesses. Substantial quantities of labor have been carried out on this connection [1], and antioxidants have been discovered to maintain operate in bone cells derived from rats [2]. A human examine had discovered an inverse correlation between antioxidant consumption and osteoporosis [3].
Due to this fact, these researchers selected two well-known antioxidants for a long-term mouse examine. The primary, methylene blue, has been within the clinic for over 100 years. This molecule readily enters cells and mitochondria, the place it has been found to react to daylight [4]. A number of experiments have discovered that it has constructive results towards age-related circumstances. For instance, one experiment discovered that it lengthens the common lifespan of feminine mice in a genetically heterogenous inhabitants [5], and one other discovered that it stops osteoarthritis from progressing in rats [6].
Whereas MitoQ, a generally taken complement, has not been discovered to increase lifespan in heterogenous mice [5], earlier work has discovered that it helps bone well being in a mouse mannequin of diabetes and in mice given a weight loss plan excessive in fats [7]. One other examine discovered it to be efficient towards superior glycation end-products (AGEs) [8] and in a mouse mannequin of bone loss attributable to tooth decay [9].
Mobile results, however not in residing animals
This examine started with administering methylene blue and MitoQ to mesenchymal stem cells (MSCs) and osteoblasts, that are accountable for developing bone. Whereas these compounds have been discovered to have mitochondrial results in these cells, there was no change in complete mobile respiration. These compounds additionally discouraged stem cells from differentiating into osteoclasts, that are accountable for eradicating bone.
The researchers administered methylene blue to feminine Black 6 mice for six or 12 months, analyzing them at 18, 24, and 30 months of age. Sadly, there have been no variations between the handled mice and the management group. The identical quantity of osteoporosis, age-related bone loss, had occurred in all of those mice relative to a different inhabitants of 5-month-old feminine mice. It was additionally discovered to haven’t any impact on the age-related lack of muscle energy often known as sarcopenia; the mice turned progressively weaker with age no matter whether or not or not they’d taken methylene blue.
The researchers then partnered with the well-known Interventions Testing Program to find out if both methylene blue or MitoQ has results on the bones of genetically heterogenous mice, administering 28 elements per million of methylene blue from 7 to 22 months or 100 elements per million of MitoQ for 4 to 22 months. Regardless of this long-term therapy, the outcomes have been totally damaging: no results on bone morphology have been present in both male or feminine mice.
Antioxidants have been well-documented as having a number of well being advantages, and it was cheap to consider that they could have had some profit on this case. Nonetheless, this examine serves as proof that they aren’t a panacea and that, in response to the researchers, “focusing on entire physique redox stability by way of systemic software of MB or MitoQ is probably not an efficient option to forestall age-related bone loss.” They as an alternative counsel that train and associated interventions could also be higher methods to handle this probably debilitating situation.
Literature
[1] Marcucci, G., Domazetovic, V., Nediani, C., Ruzzolini, J., Favre, C., & Brandi, M. L. (2023). Oxidative stress and pure antioxidants in osteoporosis: Novel preventive and therapeutic approaches. Antioxidants, 12(2), 373.
[2] Ueno, T., Yamada, M., Igarashi, Y., & Ogawa, T. (2011). N‐acetyl cysteine protects osteoblastic operate from oxidative stress. Journal of Biomedical Supplies Analysis Half A, 99(4), 523-531.
[3] Sendur, O. F., Turan, Y., Tastaban, E., & Serter, M. (2009). Antioxidant standing in sufferers with osteoporosis: a managed examine. Joint bone backbone, 76(5), 514-518.
[4] Klosowski, E. M., de Souza, B. T. L., Mito, M. S., Constantin, R. P., Mantovanelli, G. C., Mewes, J. M., … & Constantin, R. P. (2020). The photodynamic and direct actions of methylene blue on mitochondrial vitality metabolism: A stability of the helpful and dangerous results of this photosensitizer. Free Radical Biology and Drugs, 153, 34-53.
[5] Harrison, D. E., Robust, R., Allison, D. B., Ames, B. N., Astle, C. M., Atamna, H., … & Miller, R. A. (2014). Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid lengthen mouse lifespan preferentially in males. Growing older cell, 13(2), 273-282.
[6] Li, J. W., Wang, R. L., Xu, J., Solar, Ok. Y., Jiang, H. M., Solar, Z. Y., … & Shi, D. Q. (2022). Methylene blue prevents osteoarthritis development and relieves ache in rats by way of upregulation of Nrf2/PRDX1. Acta Pharmacologica Sinica, 43(2), 417-428.
[7] Li, J., He, W., Liao, B., & Yang, J. (2015). FFA-ROS-P53-mediated mitochondrial apoptosis contributes to discount of osteoblastogenesis and bone mass in sort 2 diabetes mellitus. Scientific reviews, 5(1), 12724.
[8] Mao, Y. X., Cai, W. J., Solar, X. Y., Dai, P. P., Li, X. M., Wang, Q., … & Huang, S. B. (2018). RAGE-dependent mitochondria pathway: a novel goal of silibinin towards apoptosis of osteoblastic cells induced by superior glycation finish merchandise. Cell loss of life & illness, 9(6), 674.
[9] Li, X., Zhao, Y., Peng, H., Gu, D., Liu, C., Ren, S., & Miao, L. (2022). Strong intervention for oxidative stress-induced damage in periodontitis by way of controllably launched nanoparticles that regulate the ROS-PINK1-Parkin pathway. Frontiers in Bioengineering and Biotechnology, 10, 1081977.
