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

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.

Corrigendum: The severity of acute kidney and lung injuries induced by cecal ligation and puncture is attenuated by menthol: Role of proliferating cell nuclear antigen and apoptotic markers.

[This corrects the article DOI: 10.3389/fmed.2022.904286.].

The Severity of Acute Kidney and Lung Injuries Induced by Cecal Ligation and Puncture Is Attenuated by Menthol: Role of Proliferating Cell Nuclear Antigen and Apoptotic Markers.

Objective: Sepsis-induced acute lung injury (ALI) and acute kidney injury (AKI) are major causes of mortality. Menthol is a natural compound that has anti-inflammatory and antioxidative actions. Since exaggerated inflammatory and oxidative stress are characteristics of sepsis, the aim of this study was to evaluate the effect of menthol against sepsis-induced mortality, ALI, and AKI. Methods: The cecal ligation and puncture (CLP) procedure was employed as a model of sepsis. Rats were grouped into sham, sham-Menthol, CLP, and CLP-Menthol (100 mg/kg, p.o). Key Findings: A survival study showed that menthol enhanced the survival after sepsis from 0% in septic group to 30%. Septic rats developed histological evidence of ALI and AKI. Menthol markedly suppressed sepsis induced elevation of tissue TNF-a, ameliorated sepsis-induced cleavage of caspase-3 and restored the antiapoptotic marker Bcl2. Significance: We introduced a role of the proliferating cell nuclear antigen (PCNA) in these tissues with a possible link to the damage induced by sepsis. PCNA level was markedly reduced in septic animals and menthol ameliorated this effect. Our data provide novel evidence that menthol protects against organ damage and decreases mortality in experimental sepsis.