N-Acetylcysteine Partially Rescues Heat-Stressed Skeletal Muscle Cells: A Secondary Analysis of Public Data

Résumé

Abstract Objective N-acetylcysteine (NAC) is a clinically available antioxidant with potential applications in trauma-induced hypermetabolic states, including burn injury and crush syndrome. However, its effects on heat-stressed skeletal muscle cells remain incompletely characterized. This study conducted a secondary analysis of a publicly available dataset to quantify NAC’s protective effects against heat-stress-induced cellular damage. Methods We re-analyzed a publicly available dataset (Lu J, 2024, Mendeley Data, doi:10.17632/wffrtcgbnx.1) containing 21 observations across three conditions: Control (n=3), Heat Stress only (HS, n=3), and HS with NAC at five doses (0.5-8.0 mM, n=3 per dose). The primary outcome was the protective ratio [(HS+NAC - HS) / (Control - HS)], where 1.0 indicates complete protection. Statistical analyses included one-way ANOVA, post-hoc t-tests with Bonferroni correction, Cohen’s d effect sizes, and bootstrap confidence intervals. Results Heat stress significantly reduced cell viability by 56.3% (Control: 100.0 ± 12.2 vs HS: 43.7 ± 5.1; t(4)=7.37, p=0.002, Cohen’s d=6.02). NAC demonstrated a biphasic dose-response with maximal protection at 2.0 mM (66.7 ± 14.4), yielding a protective ratio of 0.409 (95% CI: 0.146-0.675), representing 40.9% protection against heat stress damage. The comparison between HS and HS+NAC (2.0 mM) showed a large effect size (Cohen’s d = 2.12) but did not reach statistical significance (p = 0.060) due to the small sample size. One-way ANOVA confirmed overall group differences (F(2,18)=32.39, p<0.001, η 2 =0.783). Conclusions NAC provides partial protection against heat stress-induced skeletal muscle cell damage at 2.0 mM, with a large effect size suggesting clinical relevance despite limited statistical power. These preliminary findings support further investigation of NAC as an adjunct therapy in trauma-induced hypermetabolic states. All analysis code is provided for reproducibility.

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