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

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2022 Jul 11

PMID 35814769

Authors

Aliaa Anter

Al-Shaimaa F Ahmed

Asmaa S A Hammad

Waleed Hassan Almalki

Sara Mohamed Naguib Abdel Hafez

AlShaimaa W Kasem

Mohamed A El-Moselhy

Mohammad W Alrabia

Ahmed R N Ibrahim

Mahmoud El-Daly

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Platelet P2Y signalling pathway in the dysregulated immune response during sepsis.

Amoafo E, Entsie P, Kang Y, Canobbio I, Liverani E Br J Pharmacol. 2023; 181(4):532-546.

PMID: 37525937 PMC: 10830899. DOI: 10.1111/bph.16207.

Cold stimuli, hot topic: An updated review on the biological activity of menthol in relation to inflammation.

Cheng H, An X Front Immunol. 2022; 13:1023746.

PMID: 36439160 PMC: 9682018. DOI: 10.3389/fimmu.2022.1023746.

Amoafo E, Entsie P, Albayati S, Dorsam G, Kunapuli S, Kilpatrick L Front Immunol. 2022; 13:1015577.

PMID: 36405709 PMC: 9667743. DOI: 10.3389/fimmu.2022.1015577.

References

Wang X, Yu X, Yan X, Lei F, Chai Y, Jiang J . TRPM8 in the negative regulation of TNFα expression during cold stress. Sci Rep. 2017; 7:45155. PMC: 5362914. DOI: 10.1038/srep45155. View

Khalil M, Alliger K, Weidinger C, Yerinde C, Wirtz S, Becker C . Functional Role of Transient Receptor Potential Channels in Immune Cells and Epithelia. Front Immunol. 2018; 9:174. PMC: 5808302. DOI: 10.3389/fimmu.2018.00174. View

Kim M, Park S, Yang W . Inhalation of Essential Oil from Mentha piperita Ameliorates PM10-Exposed Asthma by Targeting IL-6/JAK2/STAT3 Pathway Based on a Network Pharmacological Analysis. Pharmaceuticals (Basel). 2020; 14(1). PMC: 7821947. DOI: 10.3390/ph14010002. View

Choe K, Moldovan G . Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork. Mol Cell. 2017; 65(3):380-392. PMC: 5302417. DOI: 10.1016/j.molcel.2016.12.020. View

Schulze-Osthoff K, Bakker A, Vanhaesebroeck B, Beyaert R, Jacob W, Fiers W . Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem. 1992; 267(8):5317-23. View

Deitch E . Animal models of sepsis and shock: a review and lessons learned. Shock. 1998; 9(1):1-11. DOI: 10.1097/00024382-199801000-00001. View

. Bioassay of dl-menthol for possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser. 1979; 98:1-131. View

Goldenberg N, Steinberg B, Slutsky A, Lee W . Broken barriers: a new take on sepsis pathogenesis. Sci Transl Med. 2011; 3(88):88ps25. DOI: 10.1126/scitranslmed.3002011. View

Kluck R, Bossy-Wetzel E, Green D, Newmeyer D . The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997; 275(5303):1132-6. DOI: 10.1126/science.275.5303.1132. View

10.

Yang S, Thor A, Edgerton S, Yang X . Caspase-3 mediated feedback activation of apical caspases in doxorubicin and TNF-alpha induced apoptosis. Apoptosis. 2006; 11(11):1987-97. DOI: 10.1007/s10495-006-0084-y. View

11.

Liu Y, Li A, Feng X, Jiang X, Sun X, Huang W . l-Menthol alleviates cigarette smoke extract induced lung injury in rats by inhibiting oxidative stress and inflammation nuclear factor kappa B, p38 MAPK and Nrf2 signalling pathways. RSC Adv. 2022; 8(17):9353-9363. PMC: 9078689. DOI: 10.1039/c8ra00160j. View

12.

Plevkova J, Kollarik M, Poliacek I, Brozmanova M, Surdenikova L, Tatar M . The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol. J Appl Physiol (1985). 2013; 115(2):268-74. PMC: 3727002. DOI: 10.1152/japplphysiol.01144.2012. View

13.

Sastry K, Moudgal R, Mohan J, Tyagi J, Rao G . Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem. 2002; 306(1):79-82. DOI: 10.1006/abio.2002.5676. View

14.

Buege J, Aust S . Microsomal lipid peroxidation. Methods Enzymol. 1978; 52:302-10. DOI: 10.1016/s0076-6879(78)52032-6. View

15.

Ashcroft T, Simpson J, Timbrell V . Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988; 41(4):467-70. PMC: 1141479. DOI: 10.1136/jcp.41.4.467. View

16.

Witko-Sarsat V, Mocek J, Bouayad D, Tamassia N, Ribeil J, Candalh C . Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival. J Exp Med. 2010; 207(12):2631-45. PMC: 2989777. DOI: 10.1084/jem.20092241. View

17.

Bautista D, Siemens J, Glazer J, Tsuruda P, Basbaum A, Stucky C . The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007; 448(7150):204-8. DOI: 10.1038/nature05910. View

18.

Bruemmer-Smith S, Stuber F, Schroeder S . Protective functions of intracellular heat-shock protein (HSP) 70-expression in patients with severe sepsis. Intensive Care Med. 2002; 27(12):1835-41. DOI: 10.1007/s00134-001-1131-3. View

19.

Singer M, Deutschman C, Seymour C, Shankar-Hari M, Annane D, Bauer M . The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. PMC: 4968574. DOI: 10.1001/jama.2016.0287. View

20.

Zaia M, Cagnazzo T, Feitosa K, Soares E, Faccioli L, Allegretti S . Anti-Inflammatory Properties of Menthol and Menthone in Schistosoma mansoni Infection. Front Pharmacol. 2016; 7:170. PMC: 4911957. DOI: 10.3389/fphar.2016.00170. View