Effect of Lonicera japonica extract on lactation performance, antioxidant status, and endocrine and immune function in heat-stressed mid-lactation dairy cows.

Here, we examined the effects of Lonicera japonica extract (LJE) on lactation performance, antioxidant status, and endocrine and immune function in heat-stressed mid-lactation dairy cows. Twenty-four healthy Chinese Holstein mid-lactation dairy cows, all with similar milk yield (30.0 ± 1.0 kg/d), parity (2.5 ± 0.3), and days in milk (105 ± 5 d) were allocated to 4 groups using a randomized complete block design: a negative control group (without LJE supplementation; CON) and groups that received LJE at 14, 28, and 56 g/d. The experiment lasted 10 wk over a hot summer, with a pre-feeding period of 2 wk. Cows were exposed to heat stress, as the average temperature-humidity index was greater than 72. The results showed that LJE had no effect on respiration rate; however, it reduced the rectal temperature of dairy cows experiencing heat stress in both a linear and quadratic manner; the lowest (39.03°C) was recorded for the LJE-28 group, lower than the CON group. Supplementation with LJE did not affect dry matter intake, milk yield, or milk composition. The majority of biochemical parameters in serum were unaffected by supplementation with different amounts of LJE; the exception was creatinine, which was reduced quadratically. Compared with the CON group, serum triiodothyronine concentrations increased significantly in the LJE-28 group. Addition of LJE to the diet increased thyroxine concentrations quadratically; values peaked at 18.62 ng/mL in the LJE-28 group. Furthermore, supplementation with increasing amounts of LJE quadratically increased the activity of glutathione peroxidase and total antioxidant capacity in serum but decreased concentration of malondialdehyde. Although we detected no differences in the concentrations of IgA, IgM, or cytokines, dairy cows in the LJE-28 group had higher IgG and IL-4 concentrations than did cows in the CON group. Supplementation with LJE increased concentrations of IgG and IL-4 in the serum quadratically but decreased that of IL-2. Finally, heat shock protein 72 concentrations in the serum tended to fall quadratically as the amount of LJE increased. In summary, LJE had no negative effects on lactation performance but helped to alleviate heat stress by improving antioxidant status and promoting endocrine and immune functions. Supplementation with LJE at 28 g/d is recommended for lactating dairy cows experiencing heat stress during hot summers.

Dietary supplementation of brown seaweed (Sargassum latifolium) alleviates the environmental heat stress-induced toxicity in male Barki sheep (Ovis aries).

Heat stress (HS) is the most potent environmental stressors for livestock in tropical and subtropical regions. HS induced splanchnic tissue hypoxia and intestinal oxidative damage, leading to endotoxemia and systemic inflammation. The present study evaluated and compared the modulatory effects of feeding Barki male sheep (Ovis aries) on a standard concentrated diet containing 2% or 4% of the brown seaweed (Sargassum latifolium) followed by roughage for 40 consecutive days on the toxicity-induced by exposure to severe environmental HS (temperature-humidity index = 28.55 ± 1.62). The present study showed that the diet containing Sargassum latifolium (especially 4%) modulated significantly (P < 0.05-0.001) almost all changes shown in the HS-exposed sheep including the increase in the thermo-respiratory responses (skin and rectal temperatures, and respiration rate) and the resulted dyslipidemia, anemia, and systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations). In addition, Sargassum latifolium improved significantly (P < 0.05-0.001) the body-weight gain, kidney functions (especially at the high dose), and blood antioxidant defense system (total antioxidant capacity, and the activities of catalase and superoxide dismutase) in the HS-exposed sheep, as well as protected the animals from oxidative tissue damage and the risk of atherosclerosis. In conclusion, feeding sheep with the diet containing 4% of Sargassum latifolium was safe and suitable for animal nutrition, as well as efficiently alleviated the harmful effects of the environmental HS in Barki sheep through improving the animal antioxidant defense system, and regulating the thermo-respiratory and inflammatory responses.

Effects of severe whole-body hyperthermia on ovarian hormone and extracellular Hsp72 responses in young adult women.

Background: Although acute thermal stress appears to be one of the most effective stressors that increase the intra- and extracellular concentrations of heat shock protein 72 (Hsp72), 17ß-estradiol has been shown to inhibit heat-induced Hsp72 expression. Materials and Methods: To determine whether severe whole-body hyperthermia (increase in rectal temperature up to 39.5 °C) induced by lower-body heating is a sufficient stimulus to modulate hormonal (17ß-estradiol, progesterone, prolactin, epinephrine, and norepinephrine) and extracellular Hsp72 responses, we investigated young adult women (21 ± 1 yr). Results and Conclusions: In the present study, we show that a severe whole-body hyperthermia (increase in rectal temperature of approximately 2.6 °C and heart rate of approximately 80 bpm from baseline) was sufficient to increase 17ß-estradiol, progesterone, and prolactin and catecholamine norepinephrine concentration. Moreover, we show that the concentration of extracellular Hsp72 and catecholamine epinephrine were not affected by severe whole-body hyperthermia in young adult women. From the functional point of view, expression of ovarian hormones induced by passive heat stress may have therapeutic potential for young adult women in, for example, estrogen treatment and overall women's health.

Dietary curcumin supplementation does not alter peripheral blood mononuclear cell responses to exertional heat stress.

INTRODUCTION: Curcumin reduces gut barrier damage and plasma cytokine responses to exertional heat stress. However, the role of peripheral blood mononuclear cell (PBMC) in this response remains unclear. PURPOSE: This work investigated the effect of 3 days of 500 mg/day dietary curcumin supplementation on PBMC responses to exertional heat stress in non-heat acclimated humans. METHODS: Eight participants ran (65% VO2max) for 60 min in an environmental chamber (37 °C/25% RH) two times (curcumin/placebo). Blood samples were collected pre, post, 1 h post, and 4 h post-exercise. PBMC were isolated from blood samples and the protein content of markers along the TLR4 signaling pathway (TLR4, MyD88, pNF-κB, NF-κB), indicators of cellular energy status (SIRT1 and p-AMPK), and mediators of cellular heat shock response (pHSF-1 and HSP70) were examined with Western blot. Data were analyzed with two-way (condition × time) RM-ANOVAs with Newman-Keuls post hocs. RESULTS: As compared to placebo, curcumin did not alter protein expression in PBMC (p > 0.05). However, in both study conditions at 1 h post-reductions were noted in TLR 4 (- 21.5%; p = 0.03), HSP70 (- 11.0%; p = 0.04), pAMPK (- 48.5%; p < 0.01), and SIRT1 (- 47.8%; p < 0.01). Remarkably, the ratio of pNF-κB to NF-κB was elevated in both conditions at this same timepoint (+ 75.4%; p = 0.02). CONCLUSIONS: Inflammatory protein expression in PBMC did not differ between curcumin and placebo conditions. Downregulation of pAMPK/SIRT1 and release of HSP70 to the bloodstream may compensate for reduced TLR4, allowing PBMC to maintain inflammatory capacity and preventing an "open window" during the hours following hyperthermic exercise.

Acute and chronic effects of hot water immersion on inflammation and metabolism in sedentary, overweight adults.

Regular exercise-induced acute inflammatory responses are suggested to improve the inflammatory profile and insulin sensitivity. As body temperature elevations partly mediate this response, passive heating might be a viable tool to improve the inflammatory profile. This study investigated the acute and chronic effects of hot water immersion on inflammatory and metabolic markers. Ten sedentary, overweight men [body mass index (BMI): 31.0 ± 4.2 kg/m2, mean ± SD] were immersed in water set at 39°C for 1 h (HWI) or rested for 1 h at ambient temperature (AMB). Venous blood was obtained before the session, immediately postsession, and 2 h postsession for assessment of monocyte intracellular heat shock protein-72 (iHsp72) and plasma concentrations of extracellular Hsp72 (eHsp72), interleukin-6 (IL-6), fasting glucose, insulin, and nitrite. Thereafter, participants underwent a 2-wk intervention period, consisting of 10 hot water immersion sessions (INT). Eight BMI-matched participants (BMI: 30.0 ± 2.5 kg/m2) were included as control (CON). Plasma IL-6 and nitrite concentrations were higher immediately following HWI compared with AMB (IL-6 P < 0.001, HWI: 1.37 ± 0.94 to 2.51 ± 1.49 pg/ml; nitrite P = 0.04, HWI: 271 ± 52 to 391 ± 72 nM), whereas iHsp72 expression was unchanged ( P = 0.57). In contrast to resting iHsp72 expression ( P = 0.59), fasting glucose ( P = 0.04; INT: 4.44 ± 0.93 to 3.98 ± 0.98 mmol/l), insulin ( P = 0.04; INT: 68.1 ± 44.6 to 55.0 ± 29.9 pmol/l), and eHsp72 ( P = 0.03; INT: 17 ± 41% reduction) concentrations were lowered after INT compared with CON. HWI induced an acute inflammatory response and increased nitric oxide bioavailability. The reductions in fasting glucose and insulin concentrations following the chronic intervention suggest that hot water immersion may serve as a tool to improve glucose metabolism. NEW & NOTEWORTHY A single hot water immersion (HWI) session induces an acute increase in plasma interleukin-6 and nitrite concentrations but does not acutely elevate heat shock protein-72 expression in monocytes [intracellular Hsp72 (iHsp72)]. A chronic HWI intervention reduces fasting glucose and insulin concentrations in the absence of changes in resting iHsp72. Therefore, HWI shows potential as a strategy to combat chronic low-grade inflammation and improve glucose metabolism in individuals without the physical capacity to do so using exercise.

Anti-inflammatory effect as a mechanism of effectiveness underlying the clinical benefits of pelotherapy in osteoarthritis patients: regulation of the altered inflammatory and stress feedback response.

The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis (OA) patients. This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre 'El Raposo' (Spain) in a group of 21 OA patients diagnosed with primary knee OA. Clinical assessments included pain intensity using a visual analog scale; pain, stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index; and health-related quality of life using the EuroQol-5D questionnaire. Serum inflammatory cytokine levels (IL-1ß, TNF-α, IL-8, IL-6, IL-10 and TGF-ß) were evaluated using the Bio-Plex® Luminex® system. Circulating neuroendocrine-stress biomarkers, such as cortisol and extracellular 72 kDa heat shock protein (eHsp72), were measured by ELISA. After the cycle of mud therapy, OA patients improved the knee flexion angle and OA-related pain, stiffness and physical function, and they reported a better health-related quality of life. Serum concentrations of IL-1ß, TNF-α, IL-8, IL-6 and TGF-ß, as well as eHsp72, were markedly decreased. Besides, systemic levels of cortisol increased significantly. These results confirm that the clinical benefits of mud therapy may well be mediated, at least in part, by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients. Thus, mud therapy could be an effective alternative treatment in the management of OA.

Effective microorganism - X attenuates circulating superoxide dismutase following an acute bout of intermittent running in hot, humid conditions.

This study determined the effectiveness of antioxidant supplementation on high-intensity exercise-heat stress. Six males completed a high-intensity running protocol twice in temperate conditions (TEMP; 20.4°C), and twice in hot conditions (HOT; 34.7°C). Trials were completed following7 days supplementation with 70 ml·day(-1) effective microorganism-X (EM-X; TEMPEMX or HOTEMX) or placebo (TEMPPLA or HOTPLA). Plasma extracellular Hsp72 (eHsp72) and superoxide dismutase (SOD) were measured by ELISA. eHsp72 and SOD increased pre-post exercise (p < 0.001), with greater eHsp72 (p < 0.001) increases observed in HOT (+1.5 ng·ml(-1)) compared to TEMP (+0.8 ng·ml(-1)). EM-X did not influence eHsp72 (p > 0.05). Greater (p < 0.001) SOD increases were observed in HOT (+0.22 U·ml(-1)) versus TEMP (+0.10 U·ml(-1)) with SOD reduced in HOTEMX versus HOTPLA (p = 0.001). Physiological and perceptual responses were all greater (p < 0.001) in HOT versus TEMP conditions, with no difference followed EM-X (p > 0.05). EM-X supplementation attenuated the SOD increases following HOT, potentiating its application as an ergogenic aid to ameliorate oxidative stress.

Effects of temperature-humidity index and chromium supplementation on antioxidant capacity, heat shock protein 72, and cytokine responses of lactating cows.

Heat stress adversely affects the productivity and immune status of dairy cows. The temperature-humidity index (THI) is commonly used to indicate the degree of heat stress on dairy cattle. We investigated the effects of different THI and Cr supplementation on the antioxidant capacity, the levels of heat shock protein 72 (Hsp72), and cytokine responses of lactating cows. The study used a total of 24 clinically healthy uniparous midlactation Holstein cows, which were randomly divided into 2 groups (n = 12 per group), and was conducted in 3 designated THI periods: low THI period (LTHI; THI = 56.4 ± 2.5), moderate THI period (MTHI; THI = 73.9 ± 1.7), and high THI period (HTHI; THI = 80.3 ± 1.0). The 2 groups of cows were fed corn and corn silage based basal diet supplemented chromium picolinate to provide 3.5 mg of Cr/cow daily (Cr+) or basal diet with no Cr (Cr-). The experiment was a 3 × 2 factorial design. The numbers of leukocytes (P < 0.05) and serum levels of glucose (P < 0.001) were lower; however, the serum levels of blood urea nitrogen (BUN; P < 0.001) and creatinine (P < 0.001) were greater in the MTHI and HTHI than in LTHI. The total antioxidant capacity in the serum was unaltered; an increase in superoxide dismutase activity (P < 0.001) and in serum malondialdehyde concentration (P < 0.001) was observed in the MTHI and HTHI compared with the LTHI. The high THI led to increases in serum concentrations of tumor necrosis factor-α (TNF-α; P < 0.001) and IL-10 (P < 0.05). Cows supplemented with Cr had lower (P = 0.009) serum concentrations of cholesterol but greater (P < 0.001, respectively) serum levels of Hsp72 and IL-10 compared with those without Cr supplementation in the HTHI. Western blot analysis revealed that cows supplemented with Cr had greater (P = 0.038) expression of the inhibitor of nuclear factor kappa B α (IκBα) in peripheral blood mononuclear cells (PBMC) compared with those without Cr supplementation in the HTHI, whereas the expression of Hsp72 in PBMC was unaltered. Data indicate that there is a decrease in glucose and increases in BUN and creatinine in the serum of midlactation cows under hot conditions during the summer and that these cows have a lowered oxidative capacity but an elevated antioxidant capacity. In addition, Cr may play an anti-inflammatory role in lactating cows by promoting the release of Hsp72, increasing the production of IL-10, and inhibiting the degradation of IκBα under hot conditions during the summer.

Plasma heat shock protein 72 as a biomarker of sarcopenia in elderly people.

Sarcopenia is a geriatric syndrome in which there is a decrease of muscle mass and strength with aging. In age-related loss of muscle strength, there are numerous observations supporting the assertion that neural factors mediate muscle strength. A possible contributing cause may be that aging changes systemic extracellular heat shock protein (eHsp)72 activity. The present study was designed to assess the plasma levels of eHsp72 in elderly people and to investigate its potential interaction with components of sarcopenia. A total of 665 men and women participated in an official medical health examination and an integrated health examination, including psychological and physical fitness tests. Blood samples were assayed for levels of plasma Hsp72, serum C-reactive protein, interleukin 6, tumor necrosis factor α, and regular biomedical parameters. We found that higher Hsp72 in plasma is associated with lower muscle mass, weaker grip strength, and slower walking speed, and may be a potential biomarker of sarcopenia in elderly people. This finding was supported by other results in the present study: (1) older age and shrinking body and lower hemoglobin levels, all of which characterize sarcopenia, were related to higher eHsp72 tertiles and (2) the ORs of the highest tertile of eHsp72 for the lowest tertiles of muscle mass, grip strength, and walking speed were 2.7, 2.6, and 1.8, respectively. These ORs were independent of age, sex, and the incidence of related diseases. Our results would reveal that eHsp72 in plasma is linked to sarcopenia factors and is a potential biomarker or predictor of sarcopenia.

Glutamine preserves skeletal muscle force during an inflammatory insult.

The purpose of this study was to test the hypothesis that acute glutamine (GLN) supplementation can counteract skeletal muscle contractile dysfunction occurring in response to inflammation by elevating muscle heat shock protein (Hsp) expression and reducing inflammatory cytokines. Mice received 5 mg/kg lipopolysaccharide (LPS) concurrently with 1 g/kg GLN or vehicle treatments. Plantarflexor isometric force production was measured at 2 hours post-injection. Blood and gastrocnemius muscles were collected, and serum and muscle tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and muscle Hsp70 and Hsp25 were quantified. Saline/LPS treatment was associated with a 33% reduction in maximal force and elevated serum TNF-alpha and IL-6. GLN completely prevented this force decrement with LPS. GLN was found to reduce muscle Hsp70 and IL-6, but only in the presence of LPS. GLN supplementation provides an effective, novel, clinically applicable means of preserving muscle force during acute inflammation. These data indicate that force preservation is not dependent on reductions in serum cytokines or muscle TNF-alpha, or elevated Hsp levels.

Effect of exercise with and without a thermal clamp on the plasma heat shock protein 72 response.

The contribution of heat and exercise related stress to the release of heat shock protein 72 (HSP72) is currently unknown. The purpose of the present study was to determine the combined and independent effects of heat and exercise on the extracellular (e)HSP72 response. Eleven moderately trained male volunteers [means +/- SD: age 21 +/- 4 yr; body mass 75.7 +/- 7.7 kg; maximal oxygen uptake ((.)Vo(2 max)) 57.8 +/- 3.3 ml.kg(-1).min(-1)] completed four 2-h, heat-manipulated, water-immersion trials. Trials were exercise-induced heat (EIH; rectal temperature change +2.2 degrees C), clamped exercise (CEx; 0 degrees C), passive heating (PHT; +2.3 degrees C), and control (Con; 0 degrees C). Exercise trials (EIH and CEx) comprised deep-water running at 58.5 +/- 2.4 and 59.1 +/- 1.7% (.)vo(2)max. eHSP72 and catecholamine concentrations were determined by ELISA and HPLC, respectively, pre- and postimmersion. All trials induced an eHSP72 response (P < 0.05) with postimmersion values significantly greater on EIH compared with other trials (6.0 +/- 3.4; CEx 3.8 +/- 2.6; PHT 2.7 +/- 2.1; Con 2.2 +/- 1.9 ng/ml). Exercising with a thermal clamp blunted the eHSP72 response, but postimmersion values were also greater than Con. PHT induced a large catecholamine response, but postimmersion eHSP72 values did not reach significance vs. Con. Given that exercising with a thermal clamp evoked a significant increase in plasma eHSP72 concentration, exercise-related stressors other than heat appeared influential in stimulating HSP72 release. Moreover, the catecholamine data from PHT suggest neither epinephrine nor norepinephrine was solely responsible for eHSP72 release.

Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans.

Increased levels of reactive oxygen and nitrogen species, as seen in response to exercise, challenge the cellular integrity. Important protective adaptive changes include induction of heat shock proteins (HSPs). We hypothesized that supplementation with antioxidant vitamins C (ascorbic acid) and E (tocopherol) would attenuate the exercise-induced increase of HSP72 in the skeletal muscle and in the circulation. Using randomization, we allocated 21 young men into three groups receiving one of the following oral supplementations: RRR-alpha-tocopherol 400 IU/day + ascorbic acid (AA) 500 mg/day (CEalpha), RRR-alpha-tocopherol 290 IU/day + RRR-gamma-tocopherol 130 IU/day + AA 500 mg/day (CEalphagamma), or placebo (Control). After 28 days of supplementation, the subjects performed 3 h of knee extensor exercise at 50% of the maximal power output. HSP72 mRNA and protein content was determined in muscle biopsies obtained from vastus lateralis at rest (0 h), postexercise (3 h), and after a 3-h recovery (6 h). In addition, blood was sampled for measurements of HSP72, alpha-tocopherol, gamma-tocopherol, AA, and 8-iso-prostaglandin-F2alpha (8-PGF2alpha). Postsupplementation, the groups differed with respect to plasma vitamin levels. The marker of lipid peroxidation, 8-iso-PGF2alpha, increased from 0 h to 3 h in all groups, however, markedly less (P < 0.05) in CEalpha. In Control, skeletal muscle HSP72 mRNA content increased 2.5-fold (P < 0.05) and serum HSP72 protein increased 4-fold (P < 0.05) in response to exercise, whereas a significant increase of skeletal muscle HSP72 protein content was not observed (P = 0.07). In CEalpha, skeletal muscle HSP72 mRNA, HSP72 protein, and serum HSP72 were not different from Control in response to exercise. In contrast, the effect of exercise on skeletal muscle HSP72 mRNA and protein, as well as circulating HSP72, was completely blunted in CEalphagamma. The results indicate that gamma-tocopherol comprises a potent inhibitor of the exercise-induced increase of HSP72 in skeletal muscle as well as in the circulation.