Inflammatory Stress Parameters Research Articles

Cardioprotective effect of tofisopam against isoprenaline-induced myocardial infarction in rats via modulation of NLRP3\\IL-1β\\caspase-1 pathway

Purpose Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Ischemic heart diseases, particularly acute myocardial infarction (MI), represent the most common cause of death. MI is influenced by multiple factors, including the release of inflammatory mediators. A significant percentage of individuals with CVD experience psychological effects, such as anxiety and depression, which are linked to an increased risk of coronary heart disease. Certain anti-anxiety medications have demonstrated immunomodulatory and anti-inflammatory effects. Tofisopam, a 2,3-benzodiazepine with anxiolytic properties, has been shown to exert in vitro anti-inflammatory and immunomodulatory effects. The present study investigates the potential of tofisopam as a protective adjuvant against isoprenaline-induced MI in rats and explores the possible underlying mechanisms. Methods The study included four groups: a control group, a group pretreated with tofisopam, an isoprenaline toxic group, and an isoprenaline toxic group pretreated with tofisopam. Results The findings demonstrated that isoprenaline significantly increased cardiac enzyme levels, as well as elevated oxidative and inflammatory stress parameters, along with evident apoptosis in cardiac cells. In contrast, the tofisopam-pretreated group showed a significant reversal of the cardiac damage induced by isoprenaline. Conclusions Tofisopam protects against isoprenaline-induced MI through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

A short social interaction between adult and old mice improves the homeostatic systems and increases healthy longevity.

The aging process can be influenced by environmental factors, such as the social environment. The continuous cohabitation of the chronologically old mice with adult animals improves them at the behavioral level, immune function, oxidative stress and longevity, but causes a deterioration of these parameters in adults. Therefore, the objective of the study was to study whether the coexistence for only 15min a day of old mice with adult mice, can produce that improvement and greater longevity in old animals without causing deterioration in adults. For that, old and adult CD1 female mice, after two months of that social interaction, were submitted to a behavioral battery and then peritoneal leukocytes were collected to assess several immune functions, oxidative and inflammatory stress parameters as well as catecholamine concentrations. When the adult mice reached old age, the same parameters were again analyzed. The life span of each animal was also recorded. Plasmatic concentration of oxytocin was also studied. The results showed that old mice presented better behavioral capacity, immunity and oxi-inflammatory state after this social interaction with adult animals, and consequently an extended life span. Adult mice, in general, did not show any changes after social interaction with old animals, but when they achieved old age, improvements of some parameters and of longevity were observed in comparison with animals that never had a that social interaction. In conclusion, a short social interaction between old and adult individuals can be an excellent strategy for improving in both the health state and longevity.

470 - Improving homeostatic systems and healthy longevity by intergenerational relationships: Evidences from a translational neuroscience approach

The aging process is associated with a deterioration of the physiological systems, especially the homeostatic (nervous, immune and endocrine) systems with the consequent increase in morbidity and mortality. With the aging population, increasing number of studies focus on lifestyle interventions to slow down these aging derangements. Here, animal models can be useful to assess their long-term effects and potential value taking into advantage their shorter life span. In a previous work, old animals beneficed of 2 months of continuous cohabitation with adult, with improvements on behaviour, immune function and redox state as well as a higher longevity. However, their adult counterparts showed impairments in these parameters. In the present study, this social strategy was modified with the aim to improve the homeostatic systems in both the old and the adult animals.) Animals of the experimental group with “two old ICR-CD1 female mice cohabiting 15 minutes each day for 2 months with five adult mic” were studied and compared to adult and old controls. After this time, mice were submitted to a behavioural battery of tests to analyse their sensorimotor abilities, anxiety-like behaviours, and exploratory capacities. Peritoneal leukocytes were collected and several immune functions, oxidative and inflammatory stress parameters as well as catecholamine concentrations were assessed. When the adult mice reached old age the same parameters were again analysed. The life span of each animal was also recorded. Several mice of each group were sacrificed to obtain plasma and the hormone oxytocin was evaluated. The results show that old mice presented an improvement of behavioural capacities, immune functions and lower oxidative and inflammatory stress after the two months of social interaction with adult animals, and consequently they exhibited an extended life span. Adult mice, in general, did not show any changes after social interaction, but when they achieved old age an improvement of all the parameters studied and of longevity was observed in comparison with those mice that never had a social interaction with old animals. In conclusion, a short social interaction between old and adult individuals can be an excellent strategy for improving in both the health state and longevity.

Social Environment Ameliorates Behavioral and Immune Impairments in Tyrosine Hydroxylase Haploinsufficient Female Mice.

The social environment can influence the functional capacity of nervous and immune systems, and consequently the state of health, especially in aged individuals. Adult female tyrosine hydroxylase haploinsufficient (TH-HZ) mice exhibit behavioral impairments, premature immunosenescence and oxidative- inflammatory stress. All these deteriorations are associated with a lower lifespan than wild type (WT) counterparts. The aim was to analyze whether the cohabitation with WT animals could revert or at least ameliorate the deterioration in the nervous and immune systems that female TH-HZ mice show at adult age. Female TH-HZ and WT mice at age of 3-4weeks were divided into following groups: control TH-HZ (5 TH-HZ mice in the cage; TH-HZ100%), control WT (5 WT mice in the cage; WT100%), TH-HZ > 50% and WT < 50% (5 TH-HZ with 2 WT mice in each cage) as well as TH-HZ < 50% and WT > 50% (2 TH-HZ and 5 WT mice in each cage). At the age of 37-38weeks, all mice were submitted to a battery of behavioral tests, evaluating sensorimotor abilities, exploratory capacities and anxiety-like behaviors. Subsequently, peritoneal leukocytes were extracted and several immune functions as well as oxidative and inflammatory stress parameters were analyzed. The results showed that the TH-HZ < 50% group had improved behavioral responses, especially anxiety-like behaviors, and the immunosenescence and oxidative stress of their peritoneal leukocytes were ameliorated. However, WT mice that cohabited with TH-HZ mice presented higher anxiety-like behaviors and deterioration in immune functions and in their inflammatory stress parameters. Thus, this social environment is capable of ameliorating the impairments associated with a haploinsufficiency of the th gene. Graphical Abstract.

Function, Oxidative, and Inflammatory Stress Parameters in Immune Cells as Predictive Markers of Lifespan throughout Aging.

According to the oxidative-inflammatory theory of aging, there is a link between the function, the oxidative-inflammatory stress state of immune cells, and longevity. However, it is unknown which immune cell parameters can predict lifespan and if there would be any changes in this prediction, depending on the age of the subject. Therefore, a longitudinal study in mice was performed analysing immune function (chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer (NK) activity, and lymphoproliferation capacity), antioxidant (catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities as well as reduced glutathione (GSH) concentrations), oxidant (oxidized glutathione (GSSG), superoxide anion, and malondialdehyde (MDA) concentrations), and inflammation-related markers (basal release of IL-1β, IL-6, TNF-α, and IL-10) in peritoneal leukocytes from mice at the adult, mature, old, very old, and long-lived ages (40, 56, 72, 96, and 120 ± 4 weeks of age, respectively). The results reveal that some of the investigated parameters are determinants of longevity at the adult age (lymphoproliferative capacity, lymphocyte chemotaxis, macrophage chemotaxis and phagocytosis, GPx activity, and GSH, MDA, IL-6, TNF-α, and IL-10 concentrations), and therefore, they could be proposed as markers of the rate of aging. However, other parameters are predictive of extreme longevity only at the very old age (NK activity, CAT and GR activities, and IL-6 and IL-1β concentrations), and as such, they could reflect some of the adaptive mechanisms underlying the achievement of high longevity. Nevertheless, although preliminary, the results of the present study provide a new perspective on the use of function, redox, and inflammatory parameters in immune cells as prognostic tools in aging research and represent a novel benchmark for future work aimed at prediction of lifespan.

Improvements in Behavior and Immune Function and Increased Life Span of Old Mice Cohabiting With Adult Animals.

The social environment can affect the regulatory systems, and cohabitation with sick subjects is a negative factor for the nervous and immune systems, compromising the life span. Nevertheless, the possible beneficial effects of a positive social environment on nervous and immune functions and longevity have not yet been studied. The aim of this study was to analyze several behavioral and immune function parameters and life span in old mice after their cohabitation with adult animals. Old and adult ICR-CD1 female mice were divided into three experimental groups: adult controls, old controls, and a social environment experimental group. The latter contained two old mice with five adult mice. After 2 months in these conditions, mice were submitted to a behavioral battery of tests to analyze their sensorimotor abilities, anxiety-like behaviors, and exploratory capacities. Peritoneal leukocytes were then collected, and several immune functions as well as oxidative and inflammatory stress parameters were assessed. The animals were maintained in the same conditions until natural death occurred. The results showed that old animals, after cohabitation with adult mice, presented an improvement of behavioral capacities, immune functions, and a lower oxidative and inflammatory stress. Consequently, they exhibited a higher life span.

Premature aging in behavior and immune functions in tyrosine hydroxylase haploinsufficient female mice. A longitudinal study

Aging is accompanied by impairment in the nervous, immune, and endocrine systems as well as in neuroimmunoendocrine communication. In this context, there is an age-related alteration of the physiological response to acute stress, which is modulated by catecholamine (CA), final products of the sympathetic-adreno-medullary axis. The involvement of CA in essential functions of the nervous system is consistent with the neuropsychological deficits found in mice with haploinsufficiency (hemizygous; HZ) of tyrosine hydroxylase (TH) enzyme (TH-HZ). However, other possible alterations in regulatory systems have not been studied in these animals. The aim of the present work was to analyze whether adult TH-HZ female mice presented the impairment of behavioral traits and immunological responses that occurs with aging and whether they had affected their mean lifespan. ICR-CD1 female TH-HZ and wild type (WT) mice were used in a longitudinal study. Behavioral tests were performed on adult and old mice in order to evaluate their sensorimotor abilities and exploratory capacity, as well as anxiety-like behaviors. At the ages of 2 ± 1, 4 ± 1, 9 ± 1, 13 ± 1 and 20 ± 1 months, peritoneal leukocytes were extracted and several immune functions were assessed (phagocytic capacity, Natural Killer (NK) cytotoxicity, and lymphoproliferative response to lipopolysaccharide (LPS) and concanavalin A (ConA)). In addition, several oxidative stress parameters (catalase, glutathione reductase and glutathione peroxidase activities, and reduced glutathione (GSH) concentrations as antioxidant compounds as well as xanthine oxidase activity, oxidized glutathione (GSSG) concentrations, and GSSG/GSH ratio as oxidants) were analyzed. As inflammatory stress parameters TNF-alpha and IL-10 concentrations, and TNF-alpha/IL-10 ratios as inflammatory/anti-inflammatory markers, were measured. Animals were maintained in standard conditions until their natural death. The results indicate that adult TH-HZ mice presented worse sensorimotor abilities and exploratory capacity than their WT littermates as well as greater anxiety-like behaviors. With regards to the immune system, adult TH-HZ animals exhibited lower values of phagocytic capacity, NK cytotoxicity, and lymphoproliferative response to LPS and ConA than WT mice. Moreover, immune cells of TH-HZ mice showed higher oxidative and inflammatory stress than those of WT animals. Although these differences between TH-HZ and WT, in general, decreased with aging, this premature immunosenescence and impairment of behavior of TH-HZ mice was accompanied by a shorter mean lifespan in comparison to WT counterparts. In conclusion, haploinsufficiency of th gene in female mice appears to provoke premature aging of the regulatory systems affecting mean lifespan.

No Effect of Melatonin to Modify Surgical-Stress Response after Major Vascular Surgery: A Randomised Placebo-controlled trial

Background A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia–reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress. Methods Patients received an intra-operative intravenous infusion of 50 mg melatonin or placebo. In addition, all patients received 10 mg melatonin or placebo orally the first 3 nights after surgery. Blood samples for analysis of malondialdehyde (MDA), ascorbic acid (AA), dehydroascorbic acid (DHA) and C-reactive protein (CRP) were collected preoperatively, and at 5 min, 6 h and 24 h after clamp removal (recirculation of the first leg). Results Twenty-six patients received melatonin and 24 patients received placebo. No significant differences were observed in any of the oxidative and inflammatory stress parameters. There were significantly more side effects in the melatonin group than in the placebo group. Conclusions Melatonin treatment in the perioperative period did not reduce the oxidative and inflammatory parameters measured in this study.