Experimental Models of Ischaemia-Reperfusion Injury: Animal Species, Organ-Specific Approaches, Molecular Biomarkers and Therapeutic Targets

Journal of Laboratory Animal Science and Practices, cilt.6, sa.2, ss.193-205, 2026 (Hakemli Dergi)

Ischaemia and reperfusion (I/R) injury results from the combined effects of restricted tissue

perfusion and potentially damaging consequences of blood flow restoration. Experimental

animal models are essential for investigating the cellular and molecular events underlying

I/R injury; however, their outcomes are strongly influenced by the species, target organ,

method and duration of vascular occlusion/ligation/clamping, reperfusion interval,

anaesthetic protocol, sampling time, and analytical approach. This narrative review

examines commonly used cardiac, cerebral, hepatic, renal, intestinal, pulmonary, spinal

cord, and skeletal-muscle I/R models, with emphasis on their methodological characteristics

and translational limitations. It also critically evaluates biomarkers and mechanistic

endpoints associated with oxidative and nitrosative stress, inflammation, mitochondrial

dysfunction, ionic dysregulation, autophagy, apoptosis, necroptosis, pyroptosis, and

ferroptosis. Conventional measures—including malondialdehyde, antioxidant-enzyme

activities, cytokines, caspases, and histopathological scores—remain widely used but often

lack organ specificity and are highly dependent on sampling time and assay methodology.

Emerging approaches based on microRNAs, metabolomics, proteomics, lipidomics, and

mitochondrial functional measurements may improve mechanistic resolution, although

most candidate markers require independent and cross-species validation. Reliable

interpretation therefore requires the integration of molecular, biochemical, functional, and

histological outcomes rather than reliance on a single marker. Greater standardisation of

experimental design, transparent reporting, and incorporation of animal welfare and bias-

reduction measures are necessary to improve reproducibility and clinical translation.