The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice

Hydrogen sulfide (H2S) has been shown in previous studies to cause hypothermia and hypometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which H2S triggers its effects on deep body temperature has remained unknown. We investigated the thermoregulatory response to fast-(Na2S) and slow-releasing (GYY4137) H2S donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in Trpa1 knockout (Trpa1−/−) and wild-type (Trpa1+/+) mice. Intracerebroventricular administration of Na2S (0.5–1 mg/kg) caused hypothermia in C57BL/6 mice, which was mediated by cutaneous vasodilation and decreased thermogenesis. In contrast, intraperitoneal administration of Na2S (5 mg/kg) did not cause any thermoregulatory effect. Central administration of GYY4137 (3 mg/kg) also caused hypothermia and hypometabolism. The hypothermic response to both H2S donors was significantly (p < 0.001) attenuated in Trpa1−/− mice compared to their Trpa1+/+ littermates. Trpa1 mRNA transcripts could be detected with RNAscope in hypothalamic and other brain neurons within the autonomic thermoeffector pathways. In conclusion, slow- and fast-releasing H2S donors induce hypothermia through hypometabolism and cutaneous vasodilation in mice that is mediated by TRPA1 channels located in the brain, presumably in hypothalamic neurons within the autonomic thermoeffector pathways.

Role Of Triclosan (TCS)-Containing Hand Washes In Hormonal Imbalance And Impotency

Research shows that, triclosan disrupts the biosynthesis of testosterone. when tested on isolated testicular leydig cells with various dosages, it was found out that triclosan dose-dependently decreases testosterone, and the mechanism is as follows: triclosan decreases the activity of adenylyl cyclase enzyme, resulting in the drop of cAMP (cyclic adenosine monophosphate). Another research shows that, triclosan completely hammered thyroid hormones, lowered luteinizing hormone levels, follicle stimulating hormone levels, and cholesterol synthesis. Concerns over triclosan interfering with the body‘s thyroid hor-mone metabolism led to a study that found that triclosan had a marked hypothermic effect, lowering the body temperature, and overall causing a ―nonspecific depressant effect on the central nervous system. Another study associated exposure to low levels (0.03 mi-crog/L) of triclosan with disrupted thyroid hormone. Due to the close resemblance of triclosan to certain estrogens, a more recent paper in Environment International shows that triclosan inhibits estrogen sulfotransferase in sheep placenta,an enzyme which helps metabolize the hormone and transport it to the developing fetus. The suspicion is that triclosan would be dangerous in pregnancy if enough of it gets through to the placenta to affect the enzyme. Conclusively, it is recommended that hands should be washed with detergent and warm water, or with bleach and complement with alcohol-containing hand sanitizers rather than using triclosan containing hand washes; also when selecting prod-ucts such as hand washes, antiseptic soaps, facial cleansers, toothpaste, deodorants, al-ways watch out for Triclosan trade names/chemical names on the ingredient list such as trichlorocarbonalide, irgasan®, Irgacare® and Microban®, triclosan is used as a built-in antimicrobial for product protection.

Hypothermic Effect of Acute Citral Treatment during LPS-induced Systemic Inflammation in Obese Mice: Reduction of Serum TNF-α and Leptin Levels

Citral is a mixture of monoterpenes present in the essential oil of several plants, such as Cymbopogon citratus and Zingiber officinale, possessing anti-inflammatory, anti-ulcerogenic, and antipyretic actions. We investigated the action of citral on body temperature (Tb) and inflammatory signaling in eutrophic and obese mice during Systemic Inflammation (SI) induced by Lipopolysaccharide (LPS). Thus, we assessed the effect of citral (25, 100, and 300 mg/kg) and ibuprofen in LPS-induced SI in Swiss male mice fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Following SI induction, we measured Tb and collected the serum, hypothalamus, and gastric mucosa for biochemical measurements. Acute treatment with citral decreased the Tb of both SD and HFD-fed animals. Citral (300 mg/kg) treatment caused a significantly lower Tb variation in HFD-fed animals than in those fed the SD. Citral reduced peripheral levels of tumor necrosis factor (TNF)-α in SD and HFD mice and decreased serum leptin concentration in HFD mice 90 min after the LPS challenge. Furthermore, citral also reduced interleukin (IL)-6 levels in the hypothalamus of obese mice. In summary, citral effectively reduced Tb during SI by reducing inflammatory mediators with a distinct action profile in HFD mice when compared with SD.

Influence of salidroside, a neuroactive compound of Rhodiola rosea L., on alcohol tolerance development in rats

SummaryIntroduction: In recent years, the search for potential neuroprotective properties of salidroside and its ability to influence the activity of nervous system become the subject of intense studies of many research groups. None of these studies, however, include an attempt to determine the effect of salidroside on the course of alcohol tolerancein vivo.Objective: The aim of this study was to investigate the ability of salidroside to inhibit the development of alcohol tolerance in rats, determining whether the effect of its action may occur in a dose-dependent manner, reducing both metabolic and central tolerance without affecting body temperature in control rats.Methods: Male Wistar rats were injected daily with ethanol at a dose of 3 g/kg for 9 consecutive days to produce ethanol tolerance. Salidroside in two doses (4.5 mg/kg and 45 mg/kgb.w.) orvehiculumwas administered orally. On the 1st, 3rd, 5th and 8th day a hypothermic effect of ethanol was measured, while the loss of righting reflex procedure was performed on the 2nd, 4th, 6th and 7th day. On the 9th day rats were treated with salidroside, sacrificed 1 h after ethanol injections and blood was collected for blood-ethanol concentration measurement.Results: Salidroside at a dose of 45 mg/kg inhibited the development of tolerance to hypothermic and sedative effects of ethanol, whereas insignificant elevation of blood-ethanol concentration was observed. The dose of 4.5 mg/kgb.w.had minimal effect, only small inhibition of tolerance to hypothermic action was observed. Salidroside affected neither body mass growth nor body temperature in non-alcoholic (control) rats.Conclusions: Results of the study indicate that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the central nervous system. A comprehensive explanation of the abovementioned observations requires further pharmacological and pharmacodynamic studies.

Clinical Vagus Nerve Stimulation Paradigms Induce Pronounced Brain and Body Hypothermia in Rats

Vagus nerve stimulation (VNS) is a widely used neuromodulation technique that is currently used or being investigated as therapy for a wide array of human diseases such as epilepsy, depression, Alzheimer’s disease, tinnitus, inflammatory diseases, pain, heart failure and many others. Here, we report a pronounced decrease in brain and core temperature during VNS in freely moving rats. Two hours of rapid cycle VNS (7s on/18s off) decreased brain temperature by around [Formula: see text]C, while standard cycle VNS (30[Formula: see text]s on/300[Formula: see text]s off) was associated with a decrease of around [Formula: see text]C. Rectal temperature similarly decreased by more than [Formula: see text]C during rapid cycle VNS. The hypothermic effect triggered by VNS was further associated with a vasodilation response in the tail, which reflects an active heat release mechanism. Despite previous evidence indicating an important role of the locus coeruleus-noradrenergic system in therapeutic effects of VNS, lesioning this system with the noradrenergic neurotoxin DSP-4 did not attenuate the hypothermic effect. Since body and brain temperature affect most physiological processes, this finding is of substantial importance for interpretation of several previously published VNS studies and for the future direction of research in the field.