Abstract
Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.
Highlights
Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation
Thirty-eight compounds were detected in the relative quantification of sulfurcontaining compounds using sensitive liquid chromatography coupled to tandem mass spectrometry (LC–MS/ MS), of which half were significantly different between GC and mice under microgravity in space (MG mice), and between GC and A1G mice (Fig. 1a)
Spaceflight decreased S-adenosylmethionine, cystathionine, cysteine, hypotaurine, cysteine sulfonic acid, taurine, GSH, glutathione persulfide (GS-SH), ergothioneine, hercynine, histidine, serine, N-acetylserine, homoserine, and thiamine, whereas some sulfur compounds were decreased only in microgravity in space (MG) mice compared to GC or A1G mice
Summary
Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. This method has been used to detect and compare approximately 61 chemical compounds related to sulfur metabolism in h umans[21,22]
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