Therapeutic Potential of Carnosine in Ischemia–Reperfusion Injury: A Preclinical Study in Muscle Tissue

Background: Ischemia-reperfusion (IR) injury, a process involving the disruption and subsequent restoration of blood flow, is a significant contributing factor to both cardiovascular diseases and broader tissue damage. Carnosine, a natural dipeptide notably abundant in muscle tissue and recognized for its antioxidant attributes, may offer protective benefits against the deleterious effects of IR injury. Methods: A total of 24 rats were randomly allocated into four distinct groups: control, carnosine control, IR, and Carnosine + IR. The IR and Carnosine + IR groups underwent a simulated blood flow blockage lasting 120 min, followed by 120 min of reperfusion. Animals in the carnosine-treated groups received 250 mg/kg of carnosine via intraperitoneal injection prior to the experimental procedure. Muscle tissue samples were subsequently analyzed to quantify markers indicative of oxidative stress, inflammation, and cellular demise. Results: Our findings demonstrated that, when compared to control groups, the IR group exhibited a significant elevation in key markers of oxidative stress (total oxidant status TOS, Oxidative Stress Index OSI), inflammation (myeloperoxidase MPO), and cell death (TUNEL, Necrosis, Edema). Specifically, the IR group presented with a TOS of 8.72 ± 0.97 μmol/L, an OSI of 2.03 ± 0.18, and an MPO level of 75.93 ± 5.72 U/L, contrasting with control values of 4.23 ± 0.56 μmol/L, 1.01 ± 0.13, and 43.26 ± 5.7 U/L, respectively. Histopathological assessments corroborated these findings, revealing severe necrosis (2.50 ± 0.55), edema (2.00 ± 0.63), and notable inflammatory cell infiltration (2.67 ± 0.52) within the IR group. Furthermore, apoptosis (quantified by TUNEL assay) was significantly increased to 18.83 ± 1.47% in the IR group. Carnosine administration in the Carnosine + IR group led to a substantial reduction in all these adverse markers, bringing their levels closer to those observed in the control groups. For instance, in the Carnosine + IR group, TOS decreased to 5.63 ± 0.87 μmol/L, OSI to 1.24 ± 0.25, and MPO to 55.91 ± 3.45 U/L. Similarly, histopathological scores for necrosis, edema, and inflammatory cell infiltration were markedly lower in the Carnosine + IR group. Conclusion: Our experimental findings strongly suggest that exogenously administered carnosine significantly reduces oxidative stress, suppresses inflammation, and attenuates cell death in skeletal muscle subjected to IR injury. These results highlight carnosine's promising therapeutic potential as a pharmacological agent for mitigating tissue damage in ischemic conditions.