In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 9 ( 2023-9-12), p. e0291462-
Abstract:
Both quercetin and leucine have been shown to exert moderately beneficial effects in preventing muscle atrophy induced by cancers or chemotherapy. However, the combined effects of quercetin and leucine, as well as the possible underlying mechanisms against cisplatin (CDDP)-induced muscle atrophy and cancer-related fatigue (CRF) remain unclear. To investigate the issues, male BALB/c mice were randomly assigned to the following groups for 9 weeks: Control, CDDP (3 mg/kg/week), CDDP+Q (quercetin 200 mg/kg/day administrated by gavage), CDDP+LL (a diet containing 0.8% leucine), CDDP+Q+LL, CDDP+HL (a diet containing 1.6% leucine), and CDDP+Q+HL. The results showed that quercetin in combination with LL or HL synergistically or additively attenuated CDDP-induced decreases in maximum grip strength, fat and muscle mass, muscle fiber size and MyHC level in muscle tissues. However, the combined effects on locomotor activity were less than additive. The combined treatments decreased the activation of the Akt/FoxO1/atrogin-1/MuRF1 signaling pathway (associated with muscle protein degradation), increased the activation of the mTOR and E2F-1 signaling pathways (associated with muscle protein synthesis and cell cycle/growth, respectively). The combined effects on signaling molecules present in muscle tissues were only additive or less. In addition, only Q+HL significantly increased glycogen levels compared to the CDDP group, while the combined treatments considerably decreased CDDP-induced proinflammatory cytokine and MCP-1 levels in the triceps muscle. Using tumor-bearing mice, we demonstrated that the combined treatments did not decrease the anticancer effect of CDDP. In conclusion, this study suggests that the combination of quercetin and leucine enhanced the suppressed effects on CDDP-induced muscle weakness and CRF through downregulating muscle atrophy and upregulating the glycogen level in muscle tissues without compromising the anticancer effect of CDDP. Multiple mechanisms, including regulation of several signaling pathways and decrease in proinflammatory mediator levels in muscles may contributed to the enhanced protective effect of the combined treatments on muscle atrophy.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0291462
DOI:
10.1371/journal.pone.0291462.g001
DOI:
10.1371/journal.pone.0291462.g002
DOI:
10.1371/journal.pone.0291462.g003
DOI:
10.1371/journal.pone.0291462.g004
DOI:
10.1371/journal.pone.0291462.g005
DOI:
10.1371/journal.pone.0291462.g006
DOI:
10.1371/journal.pone.0291462.g007
DOI:
10.1371/journal.pone.0291462.g008
DOI:
10.1371/journal.pone.0291462.g009
DOI:
10.1371/journal.pone.0291462.t001
DOI:
10.1371/journal.pone.0291462.s001
DOI:
10.1371/journal.pone.0291462.s002
DOI:
10.1371/journal.pone.0291462.s003
DOI:
10.1371/journal.pone.0291462.s004
DOI:
10.1371/journal.pone.0291462.s005
DOI:
10.1371/journal.pone.0291462.s006
DOI:
10.1371/journal.pone.0291462.s007
DOI:
10.1371/journal.pone.0291462.s008
DOI:
10.1371/journal.pone.0291462.s009
DOI:
10.1371/journal.pone.0291462.s010
DOI:
10.1371/journal.pone.0291462.r001
DOI:
10.1371/journal.pone.0291462.r002
DOI:
10.1371/journal.pone.0291462.r003
DOI:
10.1371/journal.pone.0291462.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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