Tissue & cell · 2026
Therapeutic efficacy of L-citrulline versus L-citrulline hydrogel in testicular ischemia/reperfusion injury: Modulation of the SIRT-1/NF-κB and NO synthesis (eNOS/iNOS) pathways.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Embaby Eman M, Megahed Aya, Elzeer Aya Aly, Mostafa Sally Abdallah, Samy Alaa, Salem Amgad E, Abdellatif Hussein, Elwakeel Eman E, Eldesoqui Mamdouh
Аннотация
BACKGROUND: Testicular torsion is a urological emergency that interrupts blood flow, resulting in ischemia/reperfusion injury (I/R I) that compromises testicular function and architecture. L-citrulline (L-Cit), a nitric oxide precursor with antioxidant capabilities, has been demonstrated to help lessen testicular injury. This study aims to provide novel insights by comparatively evaluating the immediate and effective anti-ischemic effects of free L-Cit versus its hydrogel formulation on reproductive outcomes and testicular histoarchitecture in a rat model of testicular torsion/detorsion (T/TD) injury .
MATERIALS/METHODS: Thirty-five adult male Wistar albino rats were randomly assigned to five equal-sized groups (n = 7): normal control, sham, T I/R I, T I/R I + L-Cit, T I/R I + Nano-L-Cit (NL-Cit). Testicular torsion was induced by rotating the left testis 720° for 3 h, followed by detorsion. Treatments were gavaged once at a dose of 600 mg/kg body weight 1 h before inducing detorsion. Reproductive function and testicular integrity were assessed via reproductive hormonal levels, oxidative stress and inflammatory markers, apoptotic parameters, histological and immunohistochemistry analysis after 7 days of reperfusion.
RESULTS AND DISCUSSION: Results revealed that both L-Cit and its hydrogel form significantly ameliorated T/TD-induced damage, evidenced by enhanced serum concentrations of reproductive hormones (p < 0.05). Elevated TAC, GPx, CAT, and SOD activity, along with reduced MDA and NO concentrations, indicated diminished oxidative stress. The testicular levels of TNF-α, IL-1β, caspase-3, BAX, eNOS, iNOS, and NF-κB p65 were markedly reduced, while SIRT-1 increased significantly. Histopathology investigation revealed improvement with minimal testicular lesions, and fibrosis corroborated the protective effect of L-Cit. Notably, L-Cit hydrogel demonstrated superior efficacy, likely due to sustained release and enhanced local bioavailability.
CONCLUSION: L-Cit-loaded hydrogel may be a potential therapeutic strategy for protecting testicular function after T/TD injury, outperforming free L-Cit. L-Cit may protect against T I/R I during surgical procedures by activating SIRT-1, preventing NF-κB-induced oxidative stress and inflammation, promoting NO synthesis through eNOS activation, and neutralizing iNOS production and pathogenic NO levels during the reperfusion phase. These mechanisms may reinforce the potential role of L-Cit in T I/R I protection during surgical procedures.
MATERIALS/METHODS: Thirty-five adult male Wistar albino rats were randomly assigned to five equal-sized groups (n = 7): normal control, sham, T I/R I, T I/R I + L-Cit, T I/R I + Nano-L-Cit (NL-Cit). Testicular torsion was induced by rotating the left testis 720° for 3 h, followed by detorsion. Treatments were gavaged once at a dose of 600 mg/kg body weight 1 h before inducing detorsion. Reproductive function and testicular integrity were assessed via reproductive hormonal levels, oxidative stress and inflammatory markers, apoptotic parameters, histological and immunohistochemistry analysis after 7 days of reperfusion.
RESULTS AND DISCUSSION: Results revealed that both L-Cit and its hydrogel form significantly ameliorated T/TD-induced damage, evidenced by enhanced serum concentrations of reproductive hormones (p < 0.05). Elevated TAC, GPx, CAT, and SOD activity, along with reduced MDA and NO concentrations, indicated diminished oxidative stress. The testicular levels of TNF-α, IL-1β, caspase-3, BAX, eNOS, iNOS, and NF-κB p65 were markedly reduced, while SIRT-1 increased significantly. Histopathology investigation revealed improvement with minimal testicular lesions, and fibrosis corroborated the protective effect of L-Cit. Notably, L-Cit hydrogel demonstrated superior efficacy, likely due to sustained release and enhanced local bioavailability.
CONCLUSION: L-Cit-loaded hydrogel may be a potential therapeutic strategy for protecting testicular function after T/TD injury, outperforming free L-Cit. L-Cit may protect against T I/R I during surgical procedures by activating SIRT-1, preventing NF-κB-induced oxidative stress and inflammation, promoting NO synthesis through eNOS activation, and neutralizing iNOS production and pathogenic NO levels during the reperfusion phase. These mechanisms may reinforce the potential role of L-Cit in T I/R I protection during surgical procedures.