Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

Abstract

Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

Protective Effect of Citrulline on the Hearts of Rats with Sepsis Induced by Cecal Ligation and Puncture

“…Thus, platelet count reduction can be used as an effective early warning index of the severity and prognosis of septic patients. We found that, in a previous study, exogenous Cit alleviated the release of proinflammatory cytokines (TNF- α , IL-1 β , and IL-6) in early sepsis and increased the release of late-stage anti-inflammatory cytokines (IL-4 and IL-10) to alleviate the inflammatory response of septic rats [ 4 ].…”

“…At present, the main reasons for organ damage caused by sepsis include inflammatory cytokines and oxidative stress injury. An increase in cardiomyocyte apoptosis can increase iNOS and NADPH oxidase expression as well as NO and superoxide production, thereby inducing oxidative stress and other damage [ 4 – 6 ]. Antioxidant enzymes are commonly assessed to determine the extent of cell damage after an oxidative stress response.…”

Protein from Hevea brasiliensis “Hev b 13” latex attenuates systemic inflammatory response and lung lesions in rats with sepsis

“…The greatest challenge is to mimick the clinical complexity of human sepsis and test possible therapeutic targets. The CLP method, the most widely used in scientific research, is considered the gold standard (Ercan and Ozdemir, 2015;Cai et al, 2016). In this study, the CLP model was used in rats to investigate the anti-inflammatory effects of Hev b 13 during sepsis.…”

“…These initiate an immunological cascade resulting in the release of pro-inflammatory interleukins, including the tumor necrosis factor (TNF-α), interleukin (IL) 1, IL-2, IL-6, IL-8, and IL-12, among others (Cai et al, 2016). Overproduction of these inflammatory mediators (cytokine storm) induces vasodilation, increased capillary permeability, hypotension, hemoconcentration, macromolecular leakage and edema, and may lead to multiple organ dysfunction syndrome (MODS), where the lungs are the most frequently affected (Matsuda and Hattori, 2006;Stearns-Kurosawa et al, 2011;Ates et al, 2015).…”

Оптимізація Лікування Пацієнтів З Артеріальною Гіпертензією Та Супутньою Ішемічною Хворобою Серця Із Застосуванням Тризипіну (Мельдонію)

“…Метааналіз 341 пацієнта продемонстрував, що в пацієнтів із септичним станом концентрація аргініну плазми була на 41 % менше, ніж у контрольній групі. Однак клінічні рандомізовані дослідження показали, що вживання аргініну не сприяє достовірному зменшенню госпітальної смертності та інфекційних ускладнень [17].…”