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

Asmaa I Matouk; Mahmoud El-Daly; Heba A Habib; Shaymaa Senousy; Sara Mohamed Naguib Abdel Hafez; AlShaimaa W Kasem; Waleed Hassan Almalki; Abdulaziz Alzahrani; Ahmed Alshehri; Al-Shaimaa F Ahmed

doi:10.3389/fphar.2022.952337

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

Front Pharmacol. 2022 Aug 30:13:952337. doi: 10.3389/fphar.2022.952337. eCollection 2022.

Affiliations

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minya, Egypt.
² Department of Pathology, Faculty of Medicine, Minia University, Minya, Egypt.
³ Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minya, Egypt.
⁴ Department of Pharmacology and Toxicology, Umm Al-Qura University, Makkah, Saudi Arabia.
⁵ Department of Pharmacology and Toxicology, College of Clinical Pharmacy, ‬AlBaha University, Al Bahah, Saudi Arabia.

Abstract

Liver dysfunction in sepsis is a major complication that amplifies multiple organ failure and increases the risk of death. Inflammation and oxidative stress are the main mediators in the pathophysiology of sepsis. Therefore, we investigated the role of menthol, a natural antioxidant, against sepsis-induced liver injury in female Wistar rats. Sepsis was induced by cecal ligation and puncture (CLP). Menthol (100 mg/kg) was given intragastric 2 h after CLP. Blood samples and liver tissues were collected 24 h after surgery. Menthol significantly (p < 0.05) attenuated the sepsis-induced elevation in serum liver enzymes and improved the hepatic histopathological changes. Menthol treatment significantly (p < 0.05) decreased hepatic levels of tumor necrosis factor-alpha, malondialdehyde, total nitrite, and cleaved caspase-3. It restored the hepatic levels of superoxide dismutase and reduced glutathione. Additionally, menthol significantly (p < 0.05) increased hepatic levels of B-cell lymphoma 2 (Bcl-2); an anti-apoptotic factor, and proliferating cell nuclear antigen (PCNA), a biomarker of regeneration and survival. Our results showed the therapeutic potential of menthol against liver injury induced by sepsis.

Keywords: PCNA; apoptosis; clp; hepatoprotection; tNF-alpha.