Melatonin modulates oxidative phosphorylation, hepatic and kidney autophagy-caused subclinical endotoxemia and acute ethanol-induced oxidative stress

ABSTRACT

The study establishes a link between alcoholism, inflammation state, and melatonin synthesis. The aim of our study was to evaluate the effects of melatonin on changes in the relationships between oxygen consumption (using NADH- or FAD-generated substrates of mitochondrial respiration), activities of lysosomal enzymes, such as alanyl aminopeptidase (AAP), leucyl aminopeptidase (LAP), β-N-acetylglucosaminidase (NAG), and acid phosphatase (AcP), biomarkers of oxidative stress estimated by the 2-thiobarbituric acid reactive substance (TBARS) level as a biomarker of lipid peroxidation, carbonyl derivatives as biomarkers of oxidatively protein damage, and biomarkers of energy metabolism during acute ethanol-induced stress (AES), and a low-dose lipopolysaccharide (LPS)-induced inflammatory responses in mice. Biochemical assays of lysosomal enzymes, biomarkers of oxidative stress, and parameters of energy metabolism (activities of alanine- and aspartate aminotransferases, succinate dehydrogenase, levels of lactate and pyruvate) were carried out in eight groups: 1) untreated control, 2) melatonin treatment (Mel, 10 mg/kg b.w., 10 days), 3) acute ethanol-induced stress (AES, 0.75 g/kg b.w., 10 days), 4) AES model with previous Mel treatment (10 mg/kg b.w., 10 days), 5) LPS-induced inflammation (injected once intraperitoneally, 150 μg/mouse), 6) LPS-induced inflammation with previous Mel treatment (10 mg/kg b.w., 10 days), 7) LPS-induced inflammation with AES model, 8) LPS-induced inflammation with AES model and Mel treatment (10 mg/kg b.w., 10 days). Oxidative stress caused by acute ethanol-induced intoxication and low-dose LPS-induced inflammation lead to structural and functional impairments, with alterations in oxygen consumption more prominent in kidneys than liver. Melatonin treatment had significant effects on mitochondrial oxidation of the NADH-generated substrate, and it also decreased mitochondrial ability to oxidize FAD-generated substrate and mitochondrial coupling in both LPS- and AES-induced oxidative stress. Melatonin exerts significant effect on the oxidation of the NAD-generated substrates. The increased lipid peroxidation and De Ritis ratio suggest damage to intracellular membrane integrity with combined effects of ethanol and LPS-induced toxicity, which can potentially result in irreversible tissue damage. Melatonin prevents lysosomal destruction of liver tissue and, to greater extent, kidney tissue during AES with simultaneous LPS exposure by limiting increased activity of lysosomal enzymes and resulting oxidative stress.

KEYWORDS:

• Melatonin
• oxidative stress
• oxygen consumption
• mitochondrial functioning
• ethanol-induced intoxication
• inflammation
• lysosomal enzymes

Acknowledgements

The present study was financially supported by the Pomeranian University in Słupsk and T.G. Shevchenko National University “Chernihiv Collegium”, Chernihiv, Ukraine.

We gratefully acknowledged The Visegrad Fund for supporting our study.

Authors’ contributions

The authors contributed to the following aspects of the investigation:

• idea, design of the study, revising it critically: NK

• analysis, interpretation of data: NK, HT, OL

• drafting the work: NK, HT.

Authors’ information

Prof. Natalia Kurhaluk, D.Sci. and Prof. Halyna Tkachenko, D.Sci.

Department of Zoology and Animal Physiology, Institute of Biology and Earth Sciences, Pomeranian University in Słupsk, Arciszewski Str., 22b, Słupsk, Poland,

Prof. Oleksandr Lukash, D.Sci.

Department of Ecology and Nature Protection, T.G. Shevchenko National University “Chernihiv Collegium”, Chernihiv, Ukraine.

Ethical Approval and Consent to participate

The experiments were conducted by the Guidelines of the European Union Council and the current laws in Ukraine and Poland and approved by the Ethical Commission of the National State University in Chernihiv (2612/2016).

Additional information

Funding

This work was supported within the framework of Statutory Researches of the Institute of Biology and Earth Sciences, Pomeranian University in Słupsk with cooperation with T.G. Shevchenko National University “Chernihiv Collegium”, Chernihiv, Ukraine, no. IBiNoZ/19.11.5.