Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats

Abstract

Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics.

Clinical Efficacy Analysis of Fast Rehabilitation Nursing on Pain Mitigation after Lumbar Discectomy and Bone Graft Fusion and Internal Fixation

“…Relevant studies have shown that lumbar discectomy and bone graft fusion and internal fixation can effectively mitigate the pain in patients with lumbar disc herniation. It also features low trauma, fast recovery, and simple operation [ 4 ], which makes the surgical method widely favored by patients and physicians. However, due to the lack of understanding of the knowledge of their own diseases in most patients, patients are prone to resistance to treatment, and it greatly compromises the effect of the operation [ 5 ].…”

The Prevention of Ischemia-Reperfusion Injury in Elderly Rats after Lower Limb Tourniquet Use

“…Therefore, the response of the rat musculature to ischemia-reperfusion-related events can be compared to the damage caused in humans. These studies, carried out on young adults (3–4 months), confirmed the efficacy of our device in inducing and maintaining controlled ischemia [ 51 ], as well as the usefulness of FA as a prophylactic treatment for reducing IRI-LL [ 52 ].…”

“…The functional recovery after IRI-LL was assessed using a rotarod apparatus (Panlab Harvard Apparatus, Barcelona, Spain). The rotation speed and acceleration, as well as the time for acclimatization to the rod, were the same as those indicated in previous works of our group [ 51 , 52 ]. The latency time to fall, as well as the speed of the rod at the time of the fall, were automatically recorded using the SeDaCom v2.0.03 software (Panlab Harvard Apparatus, Barcelona, Spain).…”

“…In this work, we used the same device and the same rat strain as those used in previous works published by our research group, as well as the same battery of analyses (biochemical, pathological and functional) [ 51 , 52 ]. We selected the rat as the experimental model because of the similarities between the rat’s anatomy and that of humans, comprising the same muscle groups.…”

Oxidative Stress in Chronic and Age-Related Diseases

“…Blood flow restoration triggers a sequence of biochemical processes, such as the formation of reactive oxygen species (ROS), the activation of cytokines, and the alteration of capillary permeability; this process exacerbates the cellular dysfunction suffered during the ischemic process, being the most affected tissue in the extremities. Cearra and colleagues [2] evaluated the effectiveness of folinic acid in a rodent model of lower-limb ischemia-reperfusion, emulating the characteristics, the techniques, and the duration of ischemia periods used in clinical practice when performing limb surgery under ischemic conditions. The authors concluded that the administration of folinic acid before tourniquet release could be considered a prophylactic treatment to prevent IR-induced damage.…”