Silymarin protects against sepsis-induced acute liver and kidney injury via anti-inflammatory and antioxidant mechanisms in the rat

Abstract

Sepsis is a leading cause of death among intensive care patients. During sepsis, exaggerated reaction to infection leads to massive production of reactive oxygen species and inflammatory mediators, which eventually leads to multiple organ damage. Silymarin is a well-known antioxidant and cytoprotective agent, which showed protective effects in different models of disease. Thus, we hypothesized that silymarin would be protective against sepsis-induced liver and kidney injury. Sepsis was induced in rats by the cecal ligation and puncture (CLP) method. Rats were divided into sham, CLP-non-treated and CLP treated with silymarin (100 mg/kg, i.p. 1 h following CLP). After 24 h, rats were euthanized for blood and tissue samples, which were used for assessment of MDA, NO, GSH, IL-6 and TNF-α levels and SOD activity, in addition to renal and hepatic function parameters. Survival study was conducted using another set of animals following the same previously mentioned procedure. Silymarin showed protective effects evidenced by enhanced overall survival following sepsis (80% in silymarin-treated vs. 20% in septic group), in addition to improvement of hepatic and renal function parameters and reduction of MDA, NO, IL-6 and TNF-α levels. Moreover, silymarin supported the endogenous antioxidant mechanisms via elevation of GSH levels and reinforcement of SOD activity. In conclusion, silymarin protects against sepsis-induced hepatic and renal injury, possibly via antioxidant and anti-inflammatory mechanisms.

Protective effects of menthol against sepsis-induced hepatic injury: Role of mediators of hepatic inflammation, apoptosis, and regeneration

“…In our current study, which is consistent with previous studies ( Ahmed et al, 2020 ; Al-Kadi et al, 2020 ), the induction of sepsis by CLP resulted in severe hepatic injury manifested as fatty changes, infiltration of inflammatory cells, apoptotic and necrotic hepatocyte death, as well as the dilation and congestion of the central vein. Damage to the liver tissues was confirmed by the elevation in serum levels of hepatic transaminases (ALT and AST).…”

“…It is worth mentioning, that our study lacks the measurement of other important antioxidative stress parameters such catalase and glutathione peroxidase enzyme activities. However, results from our previous work ( Ahmed et al, 2020 ; Ibrahim et al, 2020a ; Al-Kadi et al, 2020 ; Al‐Kadi et al, 2021 ; Senousy et al, 2022 ), in line with others ( Chen et al, 2012 ; Yang et al, 2018 ; Giustina et al, 2019 ; Ibrahim et al, 2020b ; Larrouyet-Sarto et al, 2020 ; Aboyoussef et al, 2021 ), showed that either enzyme alone or GSH is a good surrogate of the antioxidant capacity of the tissue, while the levels of MDA directly reflect tissue oxidative damage. Akin to its established antioxidant effects ( Rozza et al, 2014 ; Bastaki et al, 2018 ), menthol ameliorated the sepsis-induced elevation in hepatic ROS and total nitrite levels, while preserving the hepatic antioxidant GSH and SOD levels.…”

“…After the surgical procedure, the rats exhibited symptoms of illness, including piloerection, diarrhea, and malaise according to Morton and Griffiths ( Morton and Griffiths, 1985 ). In addition, similar to our previous studies ( Ibrahim et al, 2020a ; Al-Kadi et al, 2020 ; Al‐Kadi et al, 2021 ), ischemia and inflammation in the ligated cecum confirmed the induction of sepsis in CLP rats ( Supplementary Figure S1 ).…”

“…administration. The time of the drug intervention was chosen based on our preliminary study and previous reports ( Aksoy et al, 2014 ; Ibrahim et al, 2020a ; Al-Kadi et al, 2020 ; Al‐Kadi et al, 2021 ). Our preliminary studies showed the best survival results in the CLP septic rats that received 100 mg/kg menthol ( Supplementary Figure S2 ).…”

“…Increased ROS production and inflammation remain the hallmarks of hepatic damage in sepsis. Thus, efforts to control sepsis-induced liver injury focused on drugs with antioxidant and anti-inflammatory effects to prevent multiple organ damage and decrease mortality ( Ahmed et al, 2020 ; Al-Kadi et al, 2020 ).…”