Effect of Physical Exercise on the Febrigenic Signaling is Modulated by Preoptic Hydrogen Sulfide Production

Abstract

We tested the hypothesis that the neuromodulator hydrogen sulfide (H2S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H2S production rate and protein expressions of H2S-related synthases cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation. Rats run on a treadmill before receiving an intraperitoneal injection of lipopolysaccharide (LPS, 100 μg/kg) or saline. The magnitude of changes of Tb during the LPS-induced fever was found to be similar between sedentary and trained rats. In sedentary rats, H2S production was not affected by LPS. Conversely, in trained rats LPS caused a sharp increase in H2S production rate that was accompanied by an increased CBS expression profile, whereas 3-MPST and CSE expressions were kept relatively constant. Sedentary rats showed a significant LPS-induced release of cytokines (IL-1β, IL-6, and TNF-α) which was virtually abolished in the trained animals. Correlation between POA H2S and IL-6 as well as TNF-α was observed. Corticosterone levels were augmented after LPS injection in both groups. We found correlations between H2S and corticosterone, and corticosterone and IL-1β. These data are consistent with the notion that the responses to systemic inflammation are tightly regulated through adjustments in POA H2S production which may play an anti-inflammatory role downmodulating plasma cytokines levels and upregulating corticosterone release.

Increased hypothalamic hydrogen sulphide contributes to endotoxin tolerance by down‐modulating PGE2 production

“…As previously reported, 25,26 sal naive and sal non-tolerant rats had undetectable plasma TNFα levels ( Figure 4A,B). A surge in plasma TNFα was observed in LPS naive rats ( Figure 4A).…”

The Neuro Engraftment and Neuroregenerative effects of Hydrogen Sulphide Donor, Intracerebral MSCs, Ginko Biloba and Kefir in Attenuating Neuropathological hallmarks of Lipopolysaccharide induced Alzheimer’s disease Rat models

“…In accordance with our obtained findings, [66,67] reported that H2S plays an important crucial modulatory role in learning and memory functions by attenuating hippocampal damage and cognitive impairment in addition to protecting neurons against oxidative stress damage, neurotoxicity, and agitating apoptotic factors. It was also recorded that hydrogen sulphide down-regulates MAPK and tau protein expression in brain tissue of LPS induced rats by inhibiting Aβ production within neuron cells as a result of suppression of γ -secretase activity leading to a diminished of Aβ deposition and tangles formation with attenuating activated microglia and modulating marked antiinflammatory activity induced in the brain [68][69][70].…”

Antipyretic Effects of Citral and Possible Mechanisms of Action

“…Similarly, Luheshi et al [20] showed that IL-1ra (16 mg/kg, ip) administrated 1 and 2 h after LPS (100 μg/kg, ip) delays the febrile response by 30 min and significantly reduces the peak of Tb during fever. More recently, Teeling et al [27] reported that LPS (100 μg/kg, ip) causes increases in IL-1β, IL-6, TNF-α, and PGE 2 levels in serum and brain of mice, and Nogueira et al [23] demonstrated that LPS (100 μg/kg, ip) causes increases in plasma IL-1β, IL-6, and TNF-α levels of sedentary rats. However, other studies have shown that IL-1β is not essential for the immune response to LPS in mice [7,11].…”

“…Tb was measured for 5 h, starting 1 h before the treatments. These doses of LPS [23] and citral [22] were chosen on the basis of previous studies and because, when preliminary doses were tested, the thermoregulatory responses to these doses were the most consistent and repeatable.…”

“…Plasma levels of corticosterone were assessed using a specific radioimmunoassay technique, as recently described [23]. It was measured using a specific radioimmunoassay after extraction with ethanol.…”