Combination Therapy of N-Acetylcysteine and Simvastatin Reduce Malondialdehyde(MDA) Levels in Animal Models with Ischemic/Reperfusion Injury (IRI)

Abstract

Ischemic/reperfusion injury (IRI), refers to the damage caused by the restoration of blood supply to previously ischemic tissues, can cause damage to local organs as well as induce systemic damage and multiple organ failure. This study aimed to assess the potential of N-acetylcysteine (NAC) and simvastatin combination therapy in IRI prevention and treatment by assessing the level of muscle tissue malondialdehyde (MDA) and histopathological structures of gastrocnemius muscles of in animal model. Twenty-seven male Wistar strain white rats (Rattus norvegicus) were divided into three groups: (1) control group (P1); (2) treatment group that received oral allopurinol (P2); and (3) treatment group that received NAC andsimvastatin (P3). The levels of MDA and histopathology scores of gastrocnemius muscle were evaluated on the 4^th day after intervention. The study found the mean level of MDA on gastrocnemius muscle was 70.56±3.06 nmol/mg in P1, 11.94±0.69 nmol/mg in P2, and 7.91±0.62 nmol/mg in P3. ANOVA test showed a significant difference among the groups (p=0.001). Further analysis with Tamhane test showed a significant difference in MDA level between P1 and P2 (p=0.001), P1 and P3 (p=0.001), and P2 and P3 (p=0.001). Mann-Whitney test on histopathology score showed no significant difference between P1 and P2 (p=0.902), P1 and P3 (p=0.837), and P2 and P3 (p=0.681). In conclusion, combined therapy of NAC and simvastatin significantly reduced MDA levels in animal models with IRI, although no significant difference of histopathology score was observed.