Investigation of the Protective Effect of Alpha Lipoic Acid on Ischemic Reperfusion Damage in Ischemic Priapism in Rats

Priapism refers to a prolonged erection lasting more than four hours without any sexual stimulation, caused by a dysfunction of the mechanisms that regulate penile swelling, rigidity, and relaxation . Pathophysiologically, there are three main types of priapism: ischaemic, non-ischaemic, and recurrent (stuttering). Ischemic (veno-occlusive, low-flow) priapism is the most common type. Sickle cell anaemia, vasoactive drug use, haematological dyscrasias, heparin therapy, haemodialysis, malignancies (local or metastatic), hyperlipidaemia parenteral nutrition therapy, and trauma are among the many conditions that can cause priapism. Acute ischaemic priapism represents a medical emergency and may subsequently lead to erectile dysfunction (ED) . Ischemia-reperfusion (I/R) injury occurs with the resolution of priapism. Although reperfusion is a necessary mechanism for the preservation of ischaemic tissue, reperfusion itself initiates a pathophysiological process that causes injury. With I/R injury, neutrophils, inflammatory cytokines, and adhesion molecules with increased thrombogenicity are activated, and free oxygen radicals develop with massive intracellular Ca release . Oxidative stress damages the cell membrane and has harmful effects on the tissue, leading to permanent cellular injury. Alpha-lipoic acid (ALA) is an 8-carbon molecule first isolated from bovine liver in 1950 that can cross the blood-brain barrier. It may also be referred to as 1,2-dithiolane-3-pentanoic acid or thioctic acid . Alpha-lipoic acid (ALA) is a natural substance found in certain foods and also synthesised in the body. It is abundant in animal and plant tissues rich in mitochondrial complexes. Among plants, spinach, broccoli, and tomatoes contain the highest amounts of lipoic acid. In animal tissues, it is most abundant in the kidneys, heart, and liver. ALA is an enzymatic cofactor involved in glucose and lipid metabolism and regulates gene transcription. ALA also acts as an antioxidant because it not only improves internal antioxidant systems but also restores them and supports their production or cellular accessibility. It also effectively removes heavy metals responsible for oxidative stress from the bloodstream. ALA's most unique feature compared to other antioxidants is that it reacts as both a lipid and water-soluble compound . Pharmacologically, ALA improves glycaemic control and diabetes mellitus-related polyneuropathies; it also effectively reduces toxicities associated with heavy metal poisoning. As an antioxidant, ALA directly eliminates free radicals, chelates transition metal ions, increases cytosolic glutathione and vitamin C levels, and prevents toxicities associated with their depletion . It is used in preclinical studies and clinically in AIDS, renal lithiasis, ethanol intoxication, cerebral ischaemia, stroke, Parkinson's disease, skin inflammation, diabetic neuropathy, radiation damage, and cataract disease . This study will examine the efficacy of ALA in alleviating reperfusion injury in rat models of ischaemic priapism using biochemical and histopathological methods.

Literature review:

Publications on the subject published in PubMed, ClinicalKey, EAU, AUA Guide, National Thesis Centre, and Google Scholar were reviewed. Publications on ischaemic priapism within priapism were reviewed. These publications included a detailed examination of the pathophysiology, aetiology, interventions and treatments of priapism, and experimentally induced ischaemic priapism models. Publications containing biochemical properties related to alpha-lipoic acid and experimental studies used for treatment purposes were examined. Publications containing biomarker and histopathological examinations of serum and tissue samples examined in animal experimental models with induced ischaemia-reperfusion were reviewed.

Objective: The aim of this experimental study is to investigate the possible effects of alpha-lipoic acid on this condition biochemically and histopathologically by creating a 'long and painful erection' model in rats.

Inclusion criteria

• Adult male Sprague-Dawley rats weighing 350-400 g.

Exclusion criteria

• Animals with congenital anomalies, active infection, or systemic disease.
• Animals that died before completion of the experimental protocol.