Inhibition of Ferroptosis Alleviates Nanomaterial‐Induced Toxicity: A Meta‐Analysis of In Vitro and In Vivo Studies

Accumulating evidence supports ferroptosis as a key driver for nanomaterial (NM) exposure-induced toxicity. There is considerable interest in the therapeutic potential of ferroptosis inhibition for cells or animals exposed to NMs before clinical applications. This study aimed to synthesize data from published studies for achieving strong evidence about the effects of ferroptosis inhibitors. Fifty-three studies were included after searching PubMed, EMBASE and Cochrane Library databases up to October, 2025. The meta-analysis of in vitro studies (n = 51) showed treatment with ferroptosis inhibitors ferrostatin-1 (Fer-1; standardized mean difference [SMD] = 3.19; 95% confidence interval [CI] = 2.63-3.75) and deferoxamine (DFO; SMD = 3.40; 95% CI = 2.62-4.18) significantly improved the viability of cells exposed to NMs. The pooled results of in vivo studies (n = 8) demonstrated Fer-1 administration suppressed tissue cell death (SMD = -1.38; 95% CI = -2.39 to -0.37) and alleviated damages on the organ function [respiratory frequency (SMD = -1.33; 95% CI = -2.32 to -0.34); enhanced pause (SMD = -1.85; 95% CI = -2.95 to -0.75)] or the body weight (SMD = 1.28; 95% CI = 0.63-1.92) of animals exposed to NMs. The protective mechanisms of Fer-1 or DFO included iron removal (showing reduced iron levels and down-regulated TFRC), anti-oxidation (manifested as inhibited formation of L-ROS, MDA, restoration of GSH, up-regulation of GPX4, down-regulation of ACSL4 and COX2) or anti-inflammation (lowering IL-6, TNF-α and MCP-1). Accordingly, Fer-1 or DFO may be a potentially effective intervention for populations with NM exposure to prevent tissue damages.