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To our knowledge, no study has been carried out to evaluate the effects of thymol sustained administration on gut health and immune response in terms of its bioavailability in the rabbit organism. A total of 48 rabbits were randomly divided at 35 days of age into two dietary treatment groups (C/control or T/thymol at 0.025% addition). Thymol was added for 21 days and then withdrawn for 7 days. Thymol content in faeces (p < 0.001) and caecal content (p < 0.05) was significantly higher than in plasma during the thymol addition and withdrawal (2442 ± 451.4, 881.9 ± 231.3 ng/g DM and 46.2 ± 28.4 ng/ml, respectively; 149.5 ± 40.54, 45.76 ± 12.44 ng/g DM and 2.73 ± 0.45 ng/ml, respectively). Increasing of villi height to crypt depth ratio in small intestinal wall (p < 0.01), phagocytic activity in blood (p < 0.0001) and lactic acid bacteria in caecal appendix (p < 0.01) and faeces (p < 0.05) was still presented after withdrawn of thymol. The thymol at this concentration demonstrated its biological properties and was able to positively affect gut health and immune response of rabbits., (© 2021 Wiley-VCH GmbH.)

To find natural feed additives with a beneficial effect on rabbit health, thymol alone and in combination with Enterocin M were administered in drinking water for 42 days (35 -77 days of age). A total of 48 rabbits based on their weight were randomly divided into four experimental groups: C – control (basal diet), T – thymol (250 mg/L), E – Enterocin M (Ent M) (50 μL/animal/day), T + E (thymol with Ent M). Ent M (p <.05) and thymol (p <.01) separately decreased malondialdehyde in the liver. Thymol separately and in combination significantly increased phagocytic activity in the blood (p =.0051) and lactic acid in the caecum (p =.0142) and decreased coagulase-positive staphylococci in the caecum (p =.0329). Ent M separately and in combination increased immunoglobulin A content in the jejunal wall (p =.002) and decreased coliform bacteria in faeces (p =.0002). Thymol and Ent M application separately or in combination improved the antioxidant and immune response of rabbits and demonstrated an antibacterial effect. Thymol demonstrated antibacterial effect against coagulase-positive staphylococci (CoPS) the in caecum, the formation of malondialdehyde (MDA) as a product of lipid peroxidation in liver, and a stimulation effect on fermentation the processes in the caecum and on phagocytic activity in blood. Ent M decreased coliform bacteria in faeces and stimulated the production of IgA in jejunum. Ent M together with thymol improved the structure of the jejunal wall and liver function. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides general information on the possible health benefits in animals and humans of herbal additives, particularly thymol, whose phenolic group is responsible for the neutralisation of free radicals, and information concerning its detection through body action, bioavailability and mechanisms in rabbits. Plants containing thymol have been used in traditional medicine for the treatment of various diseases, such as cardiovascular diseases, cancer and diabetes. Although a great number of in vitro studies of cardiovascular and cancer diseases are available, in vivo studies that confirm these findings have not been sufficiently reported. To determine the beneficial dose, further clinical studies are necessary, with preclinical comprehensive research on animal models. The aim of this review is to describe the therapeutic effect of thymol on various human diseases, followed by its bioavailability in humans and animals. Based on our knowledge from the current literature, after thymol addition, thymol metabolites—mostly thymol sulphate and glucuronide—are detected in the plasma and urine of humans and in the plasma, intestinal content, faeces and tissues in rats, pigs, chickens, horses and rabbits after enzymatic cleavage. In rabbits, thymol absorption from the gastrointestinal tract, its distribution within the organism, its accumulation in tissues and its excretion from the organism have been described in detail. It is necessary and important for these studies to suggest the appropriate dose needed to achieve the required health benefits not only for animals but also for humans. Information from this review concerning the mode of action of thymol in animal organisms could also be applied to human medicine and may help in the utilisation of herbal medicine in humans and in veterinary healthcare. This review summarises the important aspects of thymol's effects on health and its bioavailability in organisms, particularly in rabbits. In future, herbal-based drugs must be extensively investigated in terms of their mode of action, efficiency of administration and clinical effect. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of this study was to investigate the bioavailability and metabolic path of thymol, a major constituent of Thymus vulgaris L., in the rabbit organism. Oral bioavailability is a key parameter affecting the efficacy of substances, but it is not surprising that it does not correlate satisfactorily with efficacy. The main limitation factors are rate of absorption, metabolism, and excretion processes. In this work, the thymol metabolic path in the rabbit organism was determined for the first time after its sustained oral administration. We confirm intensive absorption of thymol from the gastrointestinal tract; our results point to metabolism and accumulation in kidney tissue and intensive metabolic and excretion processes in the liver. Some metabolic processes were present also after thymol withdrawal. Thymol as a lipophilic substance was found only in trace amounts in fat and muscle tissue as a consequence of its conversion into hydrophilic metabolite and greater elimination in the rabbit organism. This paper highlights the insufficient knowledge of modes of action of plant compounds in animal organisms. The objective of this study was the detection of thymol in rabbit plasma, tissues, large intestinal content, and faeces. Forty-eight rabbits were divided into control and experimental groups (thymol 250 mg/kg feed). Thymol was administered for 21 days and then withdrawn for 7 days. Concentration of thymol in the intestinal wall (IW) was significantly higher than in plasma (p < 0.05) and liver (p < 0.05); in the kidneys it was significantly higher than in plasma (p < 0.05) and liver (p < 0.05) during thymol addition. Thymol in IW was significantly higher than in plasma also after withdrawal (p < 0.01). Significant correlation (rs = −1.000, p < 0.01) between IW and plasma points to the intensive absorption of thymol from the intestine, while the correlation between plasma and liver (rs = 0.786, p < 0.05) indicates intensive biotransformation and excretion processes in liver. Significant correlation between liver and kidney (rs = 0.738, p < 0.05) confirms the intensive metabolism of thymol in the kidney. During the withdrawal period, thymol was detected above trace amounts only in faeces, and was significantly higher than in the colon during both periods (p < 0.01). Results show intensive biotransformation of thymol in the rabbit organism. [ABSTRACT FROM AUTHOR]

Simple Summary: So far, the study of the bioactivity of thymol, a major constituent of Thymus vulgaris L., in the animal organism has received little attention. Our study could give us answers to questions about whether thymol accumulates in the rabbit organism after its sustained administration and if it is also able to exhibit its beneficial properties for a longer period. Thymol in powder form at the concentration 250-mg/kg feed was added to the rabbit diet for 21 days and withdrawn for the next seven days. We confirmed that thymol was sufficiently absorbed from the gastrointestinal tract and was able to express its biological activity not only during application but, also, after withdrawal. Further studies are needed to clarify the biotransformation and bioavailability of thymol in the rabbit organism with respect to the specific features of rabbit digestion. Thymol concentrations in rabbit plasma, intestinal wall (IW) and faeces were detected, and the effects of thymol application and withdrawal on biochemical, antioxidant parameters and fatty acids (FA) in blood (B) and muscle (M) were studied. Forty-eight rabbits were divided into two experimental groups (control, C and with thymol 250-mg/kg feed, T). Thymol was administered for 21 days (TA) and withdrawn for seven days (TW). Thymol in plasma correlated with that in the IW (Spearman′s correlation coefficient (rs) = −1.000, p = 0.0167, TA) and was detected in faeces (TA and TW). In TA alkaline phosphatase (p = 0.0183), cholesterol (p = 0.0228), malondialdehyde (p = 0.003), glutathione peroxidase (p = 0.0177) in B and lactate dehydrogenase (M, p = 0.0411) decreased; monounsaturated FA (p = 0.0104) and α-linolenic acid (p = 0.0227) in M increased. In TW urea (p = 0.0079), docosapentaenoic acid (p = 0.0069) in M increased; linoleic acid (p = 0.0070), ∑ n−6 (p = 0.0007) in M and triglycerides decreased (B, p = 0.0317). In TA and TW, the total protein (p = 0.0025 and 0.0079), creatinine (B; p = 0.0357 and 0.0159) and oleic acid (M; p = 0.0104 and 0.0006) increased. Thymol was efficiently absorbed from the intestine and demonstrated its biological activity in blood and the muscles. [ABSTRACT FROM AUTHOR]