Polyethylene Microplastics and Cardiometabolic Mitochondrial-Redox Dysfunction in Preclinical Rodent Models: A Systematic Review and Meta-Analysis of Bioenergetic and Oxidative Stress Outcomes Across Target Organs.

Polyethylene microplastics (PE-MPs), the most globally abundant plastic polymer, accumulate in rodent tissues following experimental exposure and have been implicated in multi-organ biochemical disruption. Whether mitochondrial bioenergetic failure and redox collapse represent a convergent, organ-transcendent mechanism of PE-MP toxicity has not been quantitatively established. We conducted a PRISMA 2020-guided systematic review and random-effects meta-analysis, searching four electronic databases for controlled rodent studies reporting oxidative phosphorylation enzyme activities and redox markers following PE-MP exposure. Risk of bias was evaluated with SYRCLE, and evidence certainty was graded using a preclinical adaptation of GRADE. Thirteen studies (160 experimental arms, seven organ systems) met inclusion criteria; four studies across five organs supplied quantitative TCA cycle and electron transport chain data for the primary analysis, while the remaining nine contributed redox biomarker data. PE-MPs produced large, significant suppression of all four TCA cycle enzymes (CS: g = -2.69 to -3.82; p ≤ 0.009) and electron transport chain Complexes I, III, and IV (g = -3.08 to -3.70; p < 0.0001); Complex II showed non-significant, organ-specific adaptive upregulation. Pro-oxidant markers MDA and NO rose significantly, with NO showing near-perfect cross-organ homogeneity (I2 = 4.5%). Antioxidants GSH, SOD, and CAT were markedly depleted (g = -2.48, -2.93, -3.86; p < 0.0001). After mandatory GRADE/OHAT downgrades for unclear allocation concealment and single-group data dominance, certainty was Low for ten outcomes and Very Low for six. PE-MPs elicits the potency of being a mitochondrial toxicant via coherent tripartite axis throttling of TCA cycle, electron-leak amplification of the electron transport chain, and peroxynitrite-driven antioxidant exhaustion converging across renal, cardiac, pulmonary, neural, and gonadal tissues, with cardiac and cardiopulmonary mitochondrial injury emerging as a particularly consequential. These findings establish the mitochondrial-redox axis as a defining biochemical fingerprint of PE-MP multi-organ toxicity and provide mechanistic grounding for microplastic-associated cardiovascular risk.