Computational and Preclinical Evidence of Anti-ischemic Properties of L-Carnitine-Rich Supplement via Stimulation of Anti-inflammatory and Antioxidant Events in Testicular Torsed Rats

Abstract

Ischemia-reperfusion injury is a urological emergency condition that could lead to necrosis, testicular damage subfertility, and infertility. The purpose of this study was to identify changes taking place in the rat testis at short-term (4 hr) as well as long-term (7 days) reperfusion following testicular torsion and to evaluate the effects of Proxeed Plus (PP), L-carnitine-rich antioxidant supplement, on preventing these changes using the biochemical parameters and histopathology. Thirty adult male rats were divided into five groups: in groups, 1-4 testicular ischemia was achieved by rotating the left testis 720° clockwise for 4 h and dividing into the sham, torsion/detorsion (T/D), T/D+1000 mg/kg BW PP, and T/D+5000 mg/kg BW PP groups, respectively. PP was administered intraperitoneally 30 min before detorsion while group 5 served as the normal control. All rats were sacrificed 4 h after detorsion. The same experimental design was set up, and animals were sacrificed after 7 days of detorsion. The testicular levels of human cyclooxygenase-2; tumor necrosis factor; interleukins-1β, 6, and 10; hydrogen peroxide; malonaldehyde; superoxide dismutase; catalase; glutathione transferase; glutathione peroxidase; glutathione reductase; and histopathological damage were evaluated. Our results revealed that rats in the torsion/detorsion group exhibited elevated testicular levels of oxidative markers and proinflammatory cytokines, low levels of antioxidant enzymes, and severe histological alterations relative to the control and sham groups. Treatments with 1000 and 5000 mg/kg BW of PP for 4 hr and 7 days significantly ( $p<0.05$ ) decreased the levels of the proinflammatory and oxidative markers while increasing the spermatogenesis, testicular levels of antioxidant enzymes, and anti-inflammatory cytokine (IL-10) in a dose-dependent manner. This suggested that PP exhibited anti-inflammatory and antioxidant activities against I/R testes thus serving as an effective supplement to protect against testicular assault.