The Combination of Molecular Hydrogen and Heme Oxygenase 1 Effectively Inhibits Neuropathy Caused by Paclitaxel in Mice.

Abstract

This study investigated the combined effects of hydrogen-rich water (HRW) and the heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) on paclitaxel (PTX)-induced peripheral neuropathy in male C57BL/6 mice. Low-dose co-administration produced faster and greater reductions in mechanical and thermal allodynia compared with either agent alone, and also suppressed anxiodepressive-like behaviors. In the amygdala and dorsal root ganglia, the combination attenuated NLRP3 inflammasome activation, 4-hydroxynonenal accumulation, and pro-inflammatory mediator mRNA levels. Concurrently, expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and glutamate-cysteine ligase modifier subunit was elevated, while BACH1 protein levels declined. These findings indicate a synergistic interaction between the HO-1 and H2 systems in modulating oxidative stress and inflammation associated with PTX-induced neuropathy.

Mechanism

Co-administration of HRW and CoPP activates the NRF2 antioxidant pathway, upregulating HO-1, SOD1, and glutathione-related enzymes while reducing BACH1 protein and suppressing NLRP3 inflammasome activation and 4-hydroxynonenal accumulation in dorsal root ganglia and amygdala.