Resveratrol mitigates hypercholesterolemia exacerbated hyperthermia in chronically heat-stressed rats

Background and Aim: Hypercholesterolemia (HC) is the major leading cause of cardiovascular disease worldwide. Such atherogenic aberration deeply impacts blood circulation. Resveratrol (R) is a polyphenol that has received attention as a hypolipidemic, antioxidant, and vascular agility advocate. Efficient blood redistribution is a key element in mammalian thermoregulation. We hypothesized that R treatment may aid in mitigating hyperthermic responses under both acute and chronic heat stress (HS) conditions in HC male rats. Materials and Methods: All rats were initially fitted with miniaturized thermologgers to measure core body temperature (Tcore). With a 2 × 2 factorial arrangement, four groups were randomly allotted, in which half of the animals ingested an HC diet (C+), while the other half ingested a control (C-) diet, throughout the whole study duration of 35 days. Seven rats from each dietary treatment, however, received R (R+; 13 mg/kg BW/day), while the rest received normal saline (R-) for 5 continuous days. All animals were maintained at thermoneutrality (TN; ambient temperature; Ta=23.15±0.04°C) for a period of 30 continuous days (days 0-29). On day 29, an acute HS (HS; Ta=35.86±0.37°C; for 9 nocturnal h) was imposed. Then, from day 29, a chronic HS protocol (Ta=32.28±1.00°C) was maintained until the past day of the trial (day 34), after which blood samples were drawn for analyses of platelet (PL) count, total antioxidant activity (TAO), total cholesterol (TC), triglycerides (TGs), and lipid peroxidation (LP). Results: Switching animals from TN to HS resulted in abrupt rises in Tcore. The HC diet induced a significant (p<0.01) hyperlipidemia over the control of diet-consuming rats. Interestingly, the hyperthermic response to acute HS was highly pronounced in the rats consuming the C- diet, while the C+ diet exacerbated the chronic HS-induced hyperthermia. Despite failure to improve TAO in the C+ diet, R+ treatment caused a marked (p<0.05) decline in nighttime - hyperthermia in C+ rats, likely by enhancing blood flow to extremities (for heat dissipation) as delineated by drastic downregulations of C+ related rises in PL, TC, TG, and LP (HC diet by R+ interaction; p<0.03). Conclusion: The hyperthermic response in C- groups was attributed to higher amount of feed intake than those consuming the C+ diet. Yet, the R+ improvement of thermoregulation in the C+ group was likely related to enhancement of vascular hemodynamics. Resveratrol intake mitigated chronic HS-evoked hyperthermia in rats. Such an approach is worthy to follow-up in other mammals and humans.

Circadian variability of body temperature responses to methamphetamine

Vital parameters of living organisms exhibit circadian rhythmicity. Although rats are nocturnal animals, most of the studies involving rats are performed during the day. The objective of this study was to examine the circadian variability of the body temperature responses to methamphetamine. Body temperature was recorded in male Sprague-Dawley rats that received intraperitoneal injections of methamphetamine (Meth, 1 or 5 mg/kg) or saline at 10 AM or at 10 PM. The baseline body temperature at night was 0.8°C higher than during the day. Both during the day and at night, 1 mg/kg of Meth induced monophasic hyperthermia. However, the maximal temperature increase at night was 50% smaller than during the daytime. Injection of 5 mg/kg of Meth during the daytime caused a delayed hyperthermic response. In contrast, the same dose at night produced responses with a tendency toward a decrease of body temperature. Using mathematical modeling, we previously showed that the complex dose dependence of the daytime temperature responses to Meth results from an interplay between inhibitory and excitatory drives. In this study, using our model, we explain the suppression of the hyperthermia in response to Meth at night. First, we found that the baseline activity of the excitatory drive is greater at night. It appears partially saturated and thus is additionally activated by Meth to a lesser extent. Therefore, the excitatory component causes less hyperthermia or becomes overpowered by the inhibitory drive in response to the higher dose. Second, at night the injection of Meth results in reduction of the equilibrium body temperature, leading to gradual cooling counteracting hyperthermia.

Wheel running increases hyperthermia and mortality rate following 3,4-methylenedioxymethamphetamine (MDMA) in rats

Hyperthermic responses are commonly reported in cases of human medical emergency following recreational use of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”), but a precise determination of contributing environmental factors has been elusive given the relative scarcity of threatening and fatal reactions in humans. This study was conducted to determine if elevated physical activity contributes to hyperthermic responses to MDMA in a well controlled animal model. Unrestrained male Wistar rats were monitored with minimally-invasive radiotelemetry techniques following challenge with MDMA (1.0, 5.6 and 10.0 mg/kg, s.c.). Studies were conducted in low (23-25°C) and high (27°C) ambient temperature (TA), with and without access to an activity wheel. The study confirmed dose dependent effects on body temperature, chamber activity and wheel activity which were modified by different TA conditions. Increases in wheel and home chamber activity produced by 10 mg/kg MDMA increased the magnitude of hyperthermia under 27°C TA. Furthermore, greater subject mortality was observed in the wheel-access condition compared with the no-wheel condition. These data provide direct evidence that sustained physical activity increases the hyperthermic response to MDMA and that this is associated with increased lethality. This is the first direct experimental confirmation that increased physical activity may be a risk factor for adverse reactions to MDMA in human user populations.

Concentration-dependent magnetic hyperthermic response of manganese ferrite-loaded ultrasmall graphene oxide nanocomposites

The SAR values of the magnetic nanocomposites increased by approximately two-fold when the concentration was reduced by a factor of 3.

The acute and subchronic effect of 3,4-methylenedioxymethamphetamine on body temperature in rats

Introduction. The consumption of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is known to cause severe hyperthermia in humans. This is of extreme importance since ecstasy is often consumed at 'rave' parties, where dancing takes place in a warm environment, which may exacerbate the effect of MDMA on thermoregulation. The present study was performed in order to evaluate the effects of single and repeated administration of MDMA on body temperature in Wistar rats. Material and methods. The study included 72 male Wistar rats, housed in groups of four in cages at a room temperature of 222oC. They were divided in two groups. The rats in the first group were treated with oral solution of MDMA (5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg) and their temperature was measured hourly until 8th hour. The rats in the second group were treated with oral solution of MDMA (5 mg/kg, 10 mg/kg, 20 mg/kg) every day during 15 days and their temperature was measured daily at 0th, 1st, 3rd, 5th and 8th hour. Temperature was measured by inserting a thermocouple probe 2,5 cm into the rectum. Results. Both groups showed dose dependent increase of body temperature, determined by rectal temperature measurements. The magnitude of hyperthemic response caused by subchronic administration of MDMA was markedly diminished during the experiment. Conclusion. The hyperthermic effect of MDMA was dose-dependent. The magnitude of the hyperthermic response was markedly diminished in subchronic administration.

Hyperthermia Modulates Respiratory Pacemaker Bursting Properties

Most mammals modulate respiratory frequency (RF) to dissipate heat (e.g., panting) and avoid heat stroke during hyperthermic conditions. Respiratory neural network activity recorded in an isolated brain stem-slice preparation of mice exhibits a similar RF modulation in response to hyperthermia; fictive eupneic frequency increases while inspiratory network activity amplitude and duration are significantly reduced. Here, we study the effects of hyperthermia on the activity of synaptically isolated respiratory pacemakers to examine the possibility that these changes may account for the hyperthermic RF modulation of the respiratory network. During heating, modulation of the bursting frequency of synaptically isolated pacemakers paralleled that of population bursting recorded from the intact network, whereas nonpacemaker neurons were unaffected, suggesting that pacemaker bursting may account for the temperature-enhanced RF observed at the network level. Some respiratory neurons that were tonically active at hypothermic conditions exhibited pacemaker properties at approximately the normal body temperature of eutherian mammals (36.81 ± 1.17°C; mean ± SD) and continued to burst at 40°C. At elevated temperatures (40°C), there was an enhancement of the depolarizing drive potential in synaptically isolated pacemakers, while the amplitude of integrated population activity declined. Isolated pacemaker bursting ceased at 41–42°C ( n = 5), which corresponds to temperatures at which hyperthermic-apnea typically occurs in vivo. We conclude that pacemaker properties may play an important role in the hyperthermic frequency modulation and apnea, while network effects may play important roles in generating other aspects of the hyperthermic response, such as the decreased amplitude of ventral respiratory group activity during hyperthermia.