Cellular Stress Markers Identify Multi-Organ Dysfunction Syndrome in Case-Control Study

Patients diagnosed with multiple organ dysfunction syndrome demonstrated marked increases in intracellular reactive oxygen species, altered mitochondrial membrane potential fluorescence, and loss of plasma membrane integrity compared to healthy individuals, according to a case-control study published in Molecular Biology Reports. The investigation enrolled 50 patients presenting with multiple organ dysfunction syndrome alongside 50 healthy controls to examine cellular indicators of damage. Across the cohort, researchers observed distinct cellular disturbances in the patient group, providing quantitative evidence of cellular dysfunction across multiple physiological and organ systems.

Within the study framework, multiple organ dysfunction syndrome is defined by a disruption of cellular redox homeostasis, mitochondrial dysfunction, and impairment of the plasma membrane. While these pathological disturbances are recognized characteristics of the syndrome, the authors noted that they have not been fully characterized in a quantitative manner at the individual patient level. To address this gap, the investigators applied flow cytometry techniques to quantitatively measure intracellular reactive oxygen species, mitochondrial membrane potential, and propidium iodide-positive cells in blood samples collected from the participating subjects.

Standard clinical biochemistry testing confirmed severe physiological derangement among the patients with multiple organ dysfunction syndrome relative to the control group. Blood urea concentrations in the patient cohort reached an average of 105.75 ± 48.52 milligrams per deciliter, compared to 22.57 ± 5.70 milligrams per deciliter among healthy controls. In parallel, serum creatinine levels were substantially elevated in patients with the syndrome, averaging 3.01 ± 2.75 milligrams per deciliter versus 0.75 ± 0.26 milligrams per deciliter in the control subjects. These differences in biochemical parameters were statistically significant, with p-values falling below 0.001 for all comparisons.

Flow cytometric analysis of intracellular reactive oxygen species revealed substantial oxidative stress within the patient group. Intracellular reactive oxygen species levels reached 251.66 ± 94.86 mean fluorescence intensity in patients with multiple organ dysfunction syndrome, compared to 99.40 ± 14.32 mean fluorescence intensity in healthy controls, reflecting an approximate 2.53-fold elevation with statistical significance (p < 0.001). Similarly, mitochondrial membrane potential-associated fluorescence measured 29.19 ± 6.88 mean fluorescence intensity in the patient group compared to 8.71 ± 1.77 mean fluorescence intensity in controls, representing an approximate 3.35-fold increase that also reached statistical significance (p < 0.001).

Assessment of plasma membrane integrity through propidium iodide staining showed severe cellular membrane breakdown in the patient group. The proportion of propidium iodide-positive cells reached 75.73 ± 8.84 percent in patients with multiple organ dysfunction syndrome, whereas healthy control subjects exhibited only 5.55 ± 1.89 percent positivity. This difference corresponded to an approximate 13.6-fold increase in membrane permeability among patients, with statistical significance confirmed at p < 0.001. The substantial increase in propidium iodide uptake reflected widespread loss of plasma membrane integrity among circulating cells in the syndrome cohort.

Receiver operating characteristic curve analysis demonstrated exceptional discriminative ability for all three evaluated cellular markers when distinguishing patients with multiple organ dysfunction syndrome from healthy controls. Each of the three parameters—intracellular reactive oxygen species, mitochondrial membrane potential fluorescence, and propidium iodide positivity—yielded an area under the curve of 1.00. Within this study cohort, the optimal diagnostic cut-off points identified were 129.0 for reactive oxygen species, 15.45 for mitochondrial membrane potential fluorescence, and 33.63 for propidium iodide positivity. At these established thresholds, each biomarker demonstrated 100 percent sensitivity and 100 percent specificity.

The data revealed a clear association between multiple organ dysfunction syndrome and increased oxidative stress, elevated mitochondrial dysfunction-associated fluorescence, and loss of plasma membrane integrity. In addition, statistical testing revealed a strong correlation between intracellular reactive oxygen species and mitochondrial membrane potential measurements. The investigators highlighted that this strong correlation points to a well-integrated pathway linking oxidative stress directly to mitochondrial dysfunction during the progression of cellular injury.

Based on these observations, the authors concluded that intracellular reactive oxygen species, mitochondrial membrane potential-associated fluorescence, and propidium iodide-positive cells serve as complementary markers of cellular injury in patients with multiple organ dysfunction syndrome. The researchers emphasized that these parameters could be utilized as descriptive observation markers of cellular dysfunction and injury severity. The investigators maintained that these findings reflect specific cellular alterations documented within this case-control cohort of 50 patients and 50 healthy controls.

Subject of Research: Cellular biomarkers of injury in multiple organ dysfunction syndrome

Article Title: Study of intracellular reactive oxygen species, mitochondrial membrane potential, and cell membrane integrity in patients with multi-organ dysfunction syndrome

Article References: Ahmad, S., Kumar, R., Malik, M., & Khan, A. (2026). Study of intracellular reactive oxygen species, mitochondrial membrane potential, and cell membrane integrity in patients with multi-organ dysfunction syndrome. Molecular Biology Reports, 53(1), Article 1976. https://doi.org/10.1007/s11033-026-13159-x

Image Credits: AI Generated

DOI: 10.1007/s11033-026-13159-x

Keywords: multiple organ dysfunction syndrome, reactive oxygen species, mitochondrial membrane potential, cell membrane integrity, propidium iodide, flow cytometry, oxidative stress, blood urea, serum creatinine, redox homeostasis, mitochondrial dysfunction, receiver operating characteristic, cellular injury, case-control study, plasma membrane permeability, biomarker sensitivity, biomarker specificity