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The objective of the current study was to determine the photoperiod-induced variations and the impact of exercise on oxidative stress biomarkers [2-thiobarbituric acid reactive substances (TBARS), aldehydic (AD) and ketonic (KD) derivatives of oxidatively modified proteins (OMP), total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)] and biomarkers of metabolic alterations [glucose, urea, and uric acid and the activity of lactate dehydrogenase (LDH)] in the blood of Shetland pony mares and stallions involved in recreational horseback riding. Twenty-one healthy adult Shetland ponies (11 mares and 10 stallions) aged 6.5 ± 1.4 years old from the central Pomeranian region in Poland were used in this study. Blood samples were taken once per season for one year: spring (3 April), summer (5 July), autumn (1 October) and winter (25 January). A MANOVA analysis revealed that the photoperiod factor had a leading role in alterations of these biomarkers, while the exercise and sex of the ponies exerted a lower impact. The lipid peroxidation biomarkers, for example, the plasma TBARS level, indicated the maximum adjusted coefficient of determination R 2 ad  = 0.77. Before exercise (at rest), the plasma of the stallions and mares exhibited minimum values of TBARS levels in the spring and summer photoperiods and maximum levels in autumn and winter. A statistically significant reduction in the levels of both aldehydic and ketonic derivatives of OMP in the blood of ponies was observed during the autumn and winter periods; additionally, the level of ketonic derivatives of OMP declined after exercise in spring. TAC was statistically significant in the spring and winter photoperiods both before and after exercise. SOD activity did not have a pronounced photoperiod-induced pattern but was dependent on the sex and exercise. CAT activity varied and was statistically significant only in the plasma of the mares after exercise in the spring, summer, and winter photoperiods. The minimum GPx activity in the blood of the mares before exercise (at rest) was observed in autumn, while the maximum was noted in winter and summer. Photoperiod- and exercise-induced alterations in markers of oxidative stress and antioxidant defences may contribute to the adaptation of animals to exercise, depending on sex. The seasonal variations in the antioxidant defences demonstrated in our study, as well as substrates of energy metabolism in the blood of mares and stallions, depending on exercise capacity, could be an important aspect in the ability of endogenous adaptive mechanisms of animals to react in advance to environmental changes associated with seasons.

Effects of photoperiodicity caused by both the age and individual physiological reactivity estimated by resistance to hypobaric hypoxia on the levels of lipid peroxidation, protein oxidation (aldehydic and ketonic derivatives), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and biochemical parameters of aerobic and anaerobic pathways in hepatic tissue depending on the blood melatonin level were studied. The study was carried out on 96 6- and 21-month-old male rats divided into hypoxia resistance groups (LR, low resistance, HR, high resistance). The analyses were conducted at four photoperiods: winter (January), spring (March), summer (July), and autumn (October). Our results indicate a significant effect of melatonin, i.e. over 80%, revealed by the complete statistical model of the studied biomarkers of oxidative stress and oxygen-dependent parameters of metabolism. The effects of melatonin vary with age and between photoperiods, which in turn was determined by individual physiological reactivity. In terms of the photoperiods, the melatonin content in the group of the adult animals with low resistance to hypoxia decreased from winter to summer. In a group of old animals in comparison with adults, the melatonin content in all the studied photoperiods was much lower as well, regardless of their hypoxia resistance. In the group of old animals with low resistance to hypoxia, the melatonin content decreased throughout the photoperiods as follows: winter, autumn, summer, and spring. As can be concluded, spring is a critical period for old animals, particularly those with low hypoxia resistance. The important role of melatonin in these processes was also confirmed by our correlation analysis between oxidative stress biomarkers, energy-related metabolites, and antioxidant enzymes in the hepatic tissue of rats of different ages, with different resistance to hypoxia, and in different photoperiods. The melatonin concentration in the blood of highly resistant rats was higher than in those with low resistance to hypoxia. Melatonin determines the individual constitutional level of resistance to hypoxia and is responsible for individual enzymatic antioxidative responses, depending on the four photoperiods. Our studies have shown that melatonin levels are related to the redox characteristics of antioxidant defenses against lipid peroxidation and oxidative modification of proteins in old rats with low resistance to hypoxia, compared to a group of highly resistant adults. Finally, the melatonin-related mechanisms of antioxidative protection depend on metabolic processes in hepatic tissue and exhibit photoperiodical variability in adult and old rats.

Investigation of the pathogenesis of alcoholism in humans using different methodological approaches has facilitated detection of important biological factors of consequent metabolic diseases, endocrine disorders, and other medical conditions, such as alcoholic cardiomyopathy, alcoholic hypertension, heart and vascular lesions, alcoholic liver disease, alcoholic pancreatitis, etc. Alcohol abuse leads to damage to the nervous system, which can result in neurological and mental disorders, including alcoholic polyneuropathy, psychosis, and alcohol dementia. The complexity and versatility of the harmful effects of regular alcohol consumption on the human body can be considered in the perspective of a chronobiological approach, because alcohol is chronotoxic to biological processes. As a rhythm regulator, melatonin exerts a wide range of different effects: circadian rhythm regulation, thermoregulation, sleep induction, antioxidant, immunomodulatory, and anti-stress ones. This review presents from a chronobiological perspective the impact of melatonin on alcohol intoxication in terms of mental disorders, sleep and inflammation, hepatic injury, and mitochondrial function. It discusses the main clinical effects of melatonin on alcohol injury and the main targets as a therapy for alcohol disorders. Chronobiological effects of ethanol are related to melatonin suppression that has been associated with, among others, cancer risk. Exogenous melatonin seems to be a promising hepato- and immune-protector due to its antioxidant and anti-inflammatory properties, which in combination with other medicines makes it useful to prevent alcoholic organ damage. The reason for the scientific interest in melatonin as a treatment for alcoholism is obvious; the number of cases of this pathology that gives rise to metabolic syndrome, and its subsequent transformation into steatohepatitis, liver fibrosis, and cirrhosis, is increasing worldwide. Melatonin not only exerts antioxidant effects but it exerts various other effects contributing to the management of liver conditions. This review discusses the interaction between normal and pathological processes caused by alcohol consumption and the relationship between alcohol and melatonin in these conditions.

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.

This review concerns the current knowledge of melatonin and alcohol-related disorders. Chronobiological effects of ethanol are related to melatonin suppression and in relation to inflammation, stress, free radical scavenging, autophagy and cancer risk. It is postulated that both alcohol- and inflammation-induced production of reactive oxygen species (ROS) alters cell membrane properties leading to tissue dysfunction and, subsequent further ROS production. Lysosomal enzymes are often used to assess the relationships between intensified inflammation states caused by alcohol abuse and oxidative stress as well as level of tissue damage estimated by the increased release of cellular enzymes into the extracellular space. Studies have established a link between alcoholism and desynchronosis (circadian disruption). Desynchronosis results from the disorganization of the body's circadian time structure and is an aspect of the pathology of chronic alcohol intoxication. The inflammatory conditions and the activity of lysosomal enzymes in acute alcohol poisoning or chronic alcohol-dependent diseases are in most cases interrelated. Inflammation can increase the activity of lysosomal enzymes, which can be regarded as a marker of lysosomal dysfunction and abnormal cellular integrity. Studies show alcohol toxicity is modulated by the melatonin (Mel) circadian rhythm. This hormone, produced by the pineal gland, is the main regulator of 24 h (sleep-wake cycle) and seasonal biorhythms. Mel exhibits antioxidant properties and may be useful in the prevention of oxidative stress reactions known to be responsible for alcohol-related diseases. Naturally produced Mel and exogenous sources in food can act in free radical reactions and activate the endogenous defense system. Mel plays an important role in the normalization of the post-stress state by its influence on neurotransmitter systems and the synchronization of circadian rhythms. Acting simultaneously on the neuroendocrine and immune systems, Mel optimizes homeostasis and provides protection against stress. Abbreviations: ROS, reactive oxygen species; Mel, melatonin; SRV, resveratrol; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; ANT, arylalkylamine-N-acetyltransferase; EC cells, gastrointestinal enterochromaffin cells; MT1, melatonin high-affinity nanomolecular receptor site; MT2, melatonin low-affinity nanomolecular receptor site; ROR/RZR, orphan nuclear retinoid receptors; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; TAC, total antioxidant capacity; ONOO∙ - , peroxynitrite radical; NCAM, neural cell adhesion molecules; LPO, lipid peroxidation; α-KG, α-ketoglutarate, HIF-1α, Hypoxia-inducible factor 1 -α , IL-2, interleukin-2; HPA axis, hypothalamic-pituitary-adrenal axis; Tph1, tryptophan hydroxylase 1; AA-NAT, arylalkylamine-N-acetyltransferase; AS-MT, acetylserotonin O-methyltransferase; NAG, N-acetyl-beta-D-glucosaminidase; HBA1c glycated hemoglobin; LPS, lipopolysaccharide; AAP, alanyl-aminopeptidase; β-GR, β-glucuronidase; β-GD, β-galactosidase; LAP, leucine aminopeptidase.