Clues for Antioxidant and Anti-Apoptotic Effects of Melatonin on Sepsis-Induced Hepatic Damage

16 Pages Posted: 29 Mar 2023

See all articles by Mukaddes Esrefoğlu

Mukaddes Esrefoğlu

Bezmialem Vakif University

Tugce Kalkan

Kırşehir Ahi Evran University

Ersin Karatas

Ağrı İbrahim Çeçen University

Birsen Elibol

Istanbul Medeniyet University

Rumeysa Emine Hekimoglu

Bezmialem Vakif University

Fatma Bedia Karakaya Cimen

Bezmialem Vakif University

Arzu Hanım Yay

Erciyes University

Abstract

Aim: One of the serious complications of sepsis is liver damage and liver failure. The aim of this study was to evaluate the protective and therapeutic potential of melatonin in rats with lipopolysaccharide-induced sepsis.

Main methods: Female Spraque-Dawley rats received single a dose of 7.5 mg/kg lipopolysaccharide in saline to create a 24-hour sepsis model. One of the other groups received melatonin at a dose of 10 mg/kg/day from 1 week before sepsis induction to the end of the experiment. Melatonin received the same dose of melatonin for same duration but not lipopolysaccharide. Vehicle group received the same doses of saline, the vehicle of melatonin, for the same duration. Twenty-four hours after the last injection, the rats were decapitated. By appropriate histochemical, immunohistochemical, biochemical, and molecular techniques, anti-necrotic, anti-apoptotic, anti-necroptotic, anti-inflammatory, and anti-oxidant effects of melatonin were assessed.

Key findings: Lipopolysaccharide induces oxidative stress, inflammation, necrotic, apoptotic, necroptotic cell death, thus disrupts liver functions. Melatonin found to be beneficial in terms of inhibiting intrinsic pathway of apoptosis and tissue oxidant levels, stimulating tissue antioxidant enzyme levels, and restoring hepatocyte functions.

Significance: Melatonin, at those doses and duration, failed to significantly reduce histopathological damage. Longer-term melatonin administration may produce anti-inflammatory and anti-necrotic effects.

Note:
Funding Declaration: The project was supported by the Scientific Research Unit of Bezmialem Vakıf University (BAP No:11.2018/25).

Conflicts of Interest: None

Ethical Approval: Approval for the study was granted by Bezmialem Vakıf University Local Ethics Committee for Animal Experiments (Ethic Committee No:2018/131).

Keywords: Apoptosis, necrosis, necroptosis, liver, melatonin, oxidative stress

Suggested Citation

Esrefoğlu, Mukaddes and Kalkan, Tugce and Karatas, Ersin and Elibol, Birsen and Hekimoglu, Rumeysa Emine and Cimen, Fatma Bedia Karakaya and Yay, Arzu Hanım, Clues for Antioxidant and Anti-Apoptotic Effects of Melatonin on Sepsis-Induced Hepatic Damage. Available at SSRN: https://ssrn.com/abstract=4394170 or http://dx.doi.org/10.2139/ssrn.4394170

Mukaddes Esrefoğlu

Bezmialem Vakif University ( email )

Tugce Kalkan

Kırşehir Ahi Evran University ( email )

Ersin Karatas

Ağrı İbrahim Çeçen University ( email )

Birsen Elibol

Istanbul Medeniyet University ( email )

D-100 Karayolu
Merdivenkoy Mevkii No:6/1 Goztepe/Kadıkoy
Istanbul
Turkey

Rumeysa Emine Hekimoglu (Contact Author)

Bezmialem Vakif University ( email )

Turkey

Fatma Bedia Karakaya Cimen

Bezmialem Vakif University ( email )

Arzu Hanım Yay

Erciyes University ( email )

Talas Yolu üzeri
Kayseri, 38039
Turkey

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