Role of MnSOD in propofol protection of human umbilical vein endothelial cells injured by heat stress.

PURPOSE: Heat stress stimulation can cause various injuries in human umbilical vein endothelial cells (HUVEC), including apoptotic cell death and an increase in cell permeability. Propofol (PPF), a commonly used anesthetic, is known to have an important role in antioxidation as well as organ protection. Therefore, our aim is to evaluate the protective effects of PPF on heat stress (HS)-induced oxidative stress injury and its possible mechanism of action. METHODS: For HS + PPF, cells were treated with propofol followed by 2 h heat stress at 43 °C and then 4 h incubation under normal conditions. For propofol treatment, HUVEC were cultured in serum-free Dulbecco's modified Eagle medium supplemented with 0, 10, 25, or 50 µM propofol for 6 h under normal conditions. RESULTS: During the study, we found that, in HS-induced cellular damage, the protective effect of propofol was related closely with its antioxidation properties. We further revealed that heat stress significantly reduced the level of manganese superoxide demutase (MnSOD) and Cu/Zn SOD, but that propofol could inhibit the reduction of MnSOD only. Transfection of HUVEC with MnSOD small interfering RNA (siRNA) markedly decreased the expression of MnSOD, and the protective effect of propofol in the MnSOD siRNA clones was significantly reduced. CONCLUSION: Propofol protected the heat stress-injured cells, at least partly, through upregulating MnSOD expression, effectively reducing the direct or indirect cell damage caused by oxidative stress.

Histological and enzymatic responses of Japanese flounder (Paralichthys olivaceus) and its hybrids (P. olivaceus ♀ × P. dentatus ♂) to chronic heat stress.

This study investigated the effects of long-term heat exposure on Japanese flounder (Paralichthys olivaceus) and its hybrids (P. olivaceus ♀ × summer flounder Paralichthys dentatus ♂). From 24 ± 0.5°C, temperature was increased by 1 ± 0.5°C in a day and was kept at that temperature for 5 days before next rise. Cumulative survival rate (CSR), cumulative survival rate under different temperature (CSR-T), histological alteration, and related enzyme activities were investigated. In P. olivaceus, mass mortality occurred at 29 and 32 °C (the CSR-T dropped to 42.39%), and serious gill damages appeared at 30 and 32°C. Meanwhile, the activities of superoxide dismutase (SOD), catalase (CAT), lysozyme (LZM), and pyruvate kinase (PK) declined around 29 and 32°C (except for CAT). In comparison with P. olivaceus, the CSR of the hybrids was higher, the gill kept a better structural integrity, and the activities of SOD, CAT, LZM, and PK showed tiny fluctuations. The results suggested that during the process of chronic heat stress, P. olivaceus seemed to be more sensitive to 29 and 32°C, and the manifestations in survival, histology, and enzyme activity were generally consistent. For the hybrids, the comparatively insensitivity to high temperature might imply its better heat tolerance.

Sex-based responses of plasma creatine kinase in broilers to thermoneutral constant and cyclic high temperatures.

1. The plasma creatine kinase (CK) activities of male and female broilers under different temperature regimens were studied to investigate the suitability of plasma CK as an indicator of muscle damage due to heat exposure (HE). 2. This study characterises the responses of plasma CK concentration of Arbor Acres broilers to thermoneutral (TN) constant (22°C) or warm cyclic (WC) temperatures (ranging from 27·9°C to 37·9°C). 3. The daily mean CK of the females tended to be higher than those of the males, and significant differences in plasma CK were observed between the genders during the first 5-d test period, namely 2-d TN constant and 3-d WC temperatures. 4. During a 5-d HE to the WC regimens, CK of both genders fluctuated with HE time but exhibited somewhat different profiles. Specifically, the daily mean CK of the females was significantly higher on d 5 of HE than any other daily means, whereas significant difference in daily CK of the males occurred on d 4 of HE. 5. Repetitive blood sampling over 5 d of HE had significant effects on the plasma CK of the females regardless of the number of repeated bleeding times. 6. Profiles of the plasma CK for each gender during d 1 of HE were similar to those under the TN condition, implying that heat stress affects the range of broiler plasma CK concentration but with a 1-d lag. 7. Plasma CK activities of female and male broilers showed a response to HE. However, both the gender and the time of blood sampling should be taken into account when plasma CK is used as an indicator of HE for market-size broilers.

Histochemical and histological evaluations of the effects of high incubation temperature on embryonic development of thymus and bursa of Fabricius in broiler chickens.

1. The effects of experimentally induced heat-stress on the embryonic development of bursa of Fabricius and thymus of the chicken were investigated by means of histological and enzyme histochemical methods. 2. In the experiments, 250 fertile eggs of the Ross 308 broiler strain were divided into two groups. The control eggs were maintained under optimal conditions (378 degrees C and 65 +/- 2% relative humidity, RH) during the whole incubation period. Heat stressed eggs were maintained under normal conditions (378 degrees C and 65 +/- 2% RH) until the 10th d of incubation and then exposed continuously (24 h per d) to high temperature (388 degrees C and 65 +/- 2% RH). Blood and tissue samples were taken from 10 animals of each group at d 13, 15, 18 and 21 of incubation and at d 2, 4 and 7 post-hatch. Tissue samples were processed for enzyme histochemical methods in addition to routine histological techniques. 3. The results revealed that egg temperatures were higher than incubator air temperature. Long-term heat-stress (401-406 degrees C egg temperature) retarded development of thymus and bursa of Fabricius. Peripheral blood ACP-ase and ANAE-positive lymphocyte levels of heat-stressed animals were lower than in the controls. 4. These results give some morphological evidence for immunosuppression induced by high temperature exposure during the embryonic development. Temperature distribution and air circulation in incubator should be questioned in the case of lower broiler flock immunity.

[Influence of acclimatization on serum enzyme changes in soldiers during exertional heat stress].

BACKGROUND/AIM: Exertional heat stress is common problem in military services. The aim was to exemine changes in serum concentrations of some enzymes in soldiers during exertional heat stress test (EHST) as well as the effects of 10-days passive or active acclimatization in climatic chamber. METHODS: Forty male soldiers with high aerobic capacity, performed EHST either in cool (20 degrees C, 16 degrees C Wet bulb globe temperature--WBGT), or hot (40 degrees C, 25 degrees C WBGT) environment, unacclimatized, or after 10 days of passive or active acclimation. Physiological strain was measured by tympanic temperatures (Tty) and heart rates (HR). Concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine-kinase (CK) were measured in blood samples collected before and immediately after EHST. RESULTS: Exertional heat stress test in hot conditions induced physiological heat stress (increase in Tty and HR), with significant increase in concentrations of all enzymes in unacclimatized group: ALT (42.5 +/- 4.2 before vs 48.1 +/- 3.75 U/L after EHST, p < 0.01), AST (24.9 +/- 5.1 vs 33.4 +/- 4.48 U/L, p < 0.01), LDH (160.6 +/- 20.2 vs 195.7 +/- 22.6 U/L, p < 0.001) and CK (215.5 +/- 91.2 vs 279.1 +/- 117.5 U/L, p < 0.05). In acclimatized soldiers there were no significant changes in concentrations of ALT and AST, while concentration of CK was significantly higher. Concentrations of LDH were significantly higher in all investigated groups, regardless of temperature conditions. CONCLUSION: In trained soldiers, 10-days passive or active acclimatization in climatic chamber can prevent increase in serum concentrations of ALT and AST, induced by exertional heat stress. Increase of serum concentrations of CK and LDH was induced by physical strain itself, with no additional effect of heat stress.

Glycinebetaine alleviates the inhibitory effect of moderate heat stress on the repair of photosystem II during photoinhibition.

Transformation with the bacterial gene codA for choline oxidase allows Synechococcus sp. PCC 7942 cells to accumulate glycinebetaine when choline is supplemented exogenously. First, we observed two types of protective effect of glycinebetaine against heat-induced inactivation of photosystem II (PSII) in darkness; the codA transgene shifted the temperature range of inactivation of the oxygen-evolving complex from 40-52 degrees C (with half inactivation at 46 degrees C) to 46-60 degrees C (with half inactivation at 54 degrees C) and that of the photochemical reaction center from 44-55 degrees C (with half inactivation at 51 degrees C) to 52-63 degrees C (with half inactivation at 58 degrees C). However, in light, PSII was more sensitive to heat stress; when moderate heat stress, such as 40 degrees C, was combined with light stress, PSII was rapidly inactivated, although these stresses, when applied separately, did not inactivate either the oxygen-evolving complex or the photochemical reaction center. Further our studies demonstrated that the moderate heat stress inhibited the repair of PSII during photoinhibition at the site of synthesis de novo of the D1 protein but did not accelerate the photodamage directly. The codA transgene and, thus, the accumulation of glycinebetaine alleviated such an inhibitory effect of moderate heat stress on the repair of PSII by accelerating the synthesis of the D1 protein. We propose a hypothetical scheme for the cyanobacterial photosynthesis that moderate heat stress inhibits the translation machinery and glycinebetaine protects it against the heat-induced inactivation.

Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans.

Hyperoxia induces skin vasoconstriction in humans, but the mechanism is still unclear. In the present study we examined whether the vasoconstrictor response to hyperoxia is through activated adrenergic function (protocol 1) or through inhibitory effects on nitric oxide synthase (NOS) and/or cyclooxygenase (COX) (protocol 2). We also tested whether any such vasoconstrictor effect is altered by body heating. In protocol 1 (n = 11 male subjects), release of norepinephrine from adrenergic terminals in the forearm skin was blocked locally by iontophoresis of bretylium (BT). In protocol 2, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the nonselective COX antagonist ketorolac (Keto) were separately administered by intradermal microdialysis in 11 male subjects. In the two protocols, subjects breathed 21% (room air) or 100% O(2) in both normothermia and hyperthermia. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure measured by Finapres. In protocol 1, breathing 100% O(2) decreased (P < 0.05) CVC at the BT-treated and at untreated sites from the levels of CVC during 21% O(2) breathing both in normothermia and hyperthermia. In protocol 2, the administration of l-NAME inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in both thermal conditions. The administration of Keto inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in hyperthermia but not in normothermia. These results suggest that skin vasoconstriction with hyperoxia is partly due to the decreased activity of functional NOS in normothermia and hyperthermia. We found no significant role for adrenergic mechanisms in hyperoxic vasoconstriction. Decreased production of vasodilator prostaglandins may play a role in hyperoxia-induced cutaneous vasoconstriction in heat-stressed humans.

Chromatographic characterization of substance P endopeptidase in the rat brain reveals affected enzyme activity following heat stress.

This paper describes a study of substance P endopeptidase (SPE)-like activity in various regions of the brain from male rats subjected to heat stress (HS). The enzyme activity was found to be affected in several brain areas including cerebellum, cerebral cortex, hippocampus, hypothalamus[sol ]thalamus and the spinal cord following HS. Significant increases in SPE activity were observed in, for example, hippocampus and the spinal cord. SPE-containing extracts from hippocampus were pooled and subsequently purified by size exclusion chromatography (using a Superdex 75 HR column) and by anion-exchange chromatography (using Resource Q column). The gel permeation chromatography separated the SPE-like activity into two fractions, one of which was suggested to be identical to neutral endopeptidase owing to its molecular size and inhibitory profile. The other active enzyme fraction behaved in conformity with SPE, previously identified in human cerebrospinal fluid. The activity of the purified fraction of these two enzymes was found to be increased (27%) in HS-treated animals.

Thiol supplementation in aged animals alters antioxidant enzyme activity after heat stress.

Declines in oxidative and thermal stress tolerance are well documented in aging systems. It is thought that these alterations are due in part to reductions in antioxidant defenses. Although intracellular thiols are major redox buffers, their role in maintaining redox homeostasis is not completely understood, particularly during aging, where the reliance on antioxidant enzymes and proteins may be altered. To determine whether thiol supplementation improved the antioxidant enzyme profile of aged animals after heat stress, young and old Fischer 344 rats were treated with N-acetylcysteine (NAC; 4 mmol/kg ip) 2 h before heat stress. Liver tissue was collected before and 0, 30, and 60 min after heat stress. Aging was associated with a significant decline in tissue cysteine and glutathione (GSH) levels. There was also an age-related decrease in copper-zinc superoxide dismutase activity. Heat stress did not alter liver GSH, glutathione disulfide, or antioxidant enzyme activity. With NAC treatment, old animals took up more cysteine than young animals as reflected in an increase in liver GSH and a corresponding decrease in glutamate cysteine ligase activity. Catalase activity increased after NAC treatment in both age groups. Copper-zinc superoxide dismutase activity did not change with heat stress or drug treatment, whereas manganese superoxide dismutase activity was increased in old animals only. These data indicate that GSH synthesis is substrate limited in old animals. Furthermore, aged animals were characterized by large fluctuations in antioxidant enzyme balance after NAC treatment, suggesting a lack of fine control over these enzymes that may leave aged animals susceptible to subsequent stress.

Hyperthermia-induced proteasome inhibition and loss of androgen receptor expression in human prostate cancer cells.

Prostate cancer is the second leading cause of death in men in western countries and is usually treated by surgery and/or radiotherapy. More recently, hyperthermia has been introduced into clinical trials investigating a possible effect in the first-line treatment of prostate cancer. However, the molecular mechanisms of hyperthermia are not completely understood. In this study, we investigated the effects of hyperthermia on proteasome function and its significance for signal transduction, cell death and androgen receptor (AR) expression in PC-3, LnCaP, and DU-145 human and TRAMP-C2 murine prostate cancer cells. Hyperthermia caused apoptosis and radiosensitization and decreased 26S proteasome activity in all three human cell lines to about 40% of untreated control cells. 20S proteasome activity was not affected by heat. Heat treatment inhibited constitutive and radiation-induced activation of nuclear factor kappaB caused by stabilization of IkappaB. Although stabilization of AR by proteasome inhibitors has been reported previously, AR protein levels in LnCaP cells decreased dramatically after heat. Our data suggest that inhibition of proteasome function and dependent signal transduction pathways might be a major molecular mechanisms of heat-induced apoptosis and radiosensitization. Hyperthermia abrogates AR expression in androgen-dependent cells and might thus promote malignant progression of prostate cancer.

Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation.

Recurrent herpes virus infection, in which the virus reactivates from the nervous system and causes painful lesions in peripheral tissues, is a significant clinical problem. Our recent studies showing that the amount of cyclooxygenase 2 (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib, have indicated that the prostaglandin synthesis pathway--and in particular COX-2--may be an intermediate in the pathway to herpes viral reactivation. To further study this process, we infected the corneas of mice using topical application to a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1 (HSV-1) latency to be established in the trigeminal ganglia. Prior to the induction of viral reactivation, the mice were treated orally with celecoxib. Treated and untreated mice were induced to undergo reactivation by immersion in 43 degrees C water for 10 min. The shedding of virus at the ocular surface was determined by culturing ocular swabs with indicator cells. The presence of infectious virus in the trigeminal ganglion was evaluated by incubating ganglion homogenates with indicator cells and observing for cytopathic effect. Celecoxib treatment significantly suppressed viral reactivation when given prophylactically by the gastrointestinal route. The numbers of corneas and ganglia containing infectious virus were significantly lower in the celecoxib-treated animals, compared to the placebo-treated mice. These experiments demonstrate that a selective COX-2 inhibitor can suppress hyperthermic stress-induced herpes viral reactivation in the nervous system. It may be possible to use COX-2 inhibitors to prevent viral reactivation in high-risk patients by drug prophylaxis.

Granzyme N, a novel granzyme, is expressed in spermatocytes and spermatids of the mouse testis.

We cloned a cDNA for a novel granzyme, granzyme N (Gzmn), from a mouse testes cDNA library. The testes contained two distinct species of Gzmn mRNA, one of which codes for a complete protein of 248 amino acids with three essential residues required for catalytic activity. The Gzmn mRNA was specifically expressed in the testes of adult mice. The Gzmn expression was found to initiate in the testes at 3 wk of age and to become more prominent as the animal reached sexual maturity. In situ hybridization analysis revealed that both spermatocytes and spermatids of the adult mouse testes express Gzmn mRNA. Consistent with these findings, the protein was immunohistochemically detected in the spermatocytes and spermatids, although some of the germ cells showed no positive staining. Gzmn was demonstrated to be a secretory and N-glycosylated protein that exists in two protein forms in the testes extract. In the cryptorchid testes, the expression of Gzmn transcript was drastically reduced on Postoperative Day 10, whereas the protein level was gradually decreased starting on Day 6. The local heating (43 degrees C, 20 min) of the testes did not change the Gzmn expression level at either 8 or 16 h after treatment. These results suggest that Gzmn is not involved in the process of germ cell apoptosis induced by heat shock, but that it may be involved in spermatogenesis in the mouse testes.

Human ACE I/D polymorphism is associated with individual differences in exercise heat tolerance.

We hypothesized that there is an association between the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism with the variability in exercise heat tolerance in humans. Fifty-eight Caucasian men were exposed to a 2-h exercise heat-tolerance test. We analyzed the association between their heat-tolerance levels with the ACE DD (n = 25) and I+ (n = 33) genotypes and with various anthropometrical parameters and aerobic fitness. It was found that the relative changes in body core temperature, heat storage, and heart rate during the 120-min exposure to exercise heat stress was consistently lower in the I+ genotype group compared with the DD genotype group (0.8 +/- 0.2 vs. 1 +/- 0.1 degrees C, P < 0.05; 17.7 +/- 1.8 vs. 19.8 +/- 1.3 W/M(2), P < 0.05; and 33 +/- 7 vs. 44 +/- 5 beats/min, respectively, P = 0.06). No significant association was found between heat strain response and the anthropometrical measurements or aerobic fitness in the various genotype groups. We suggest that the ACE I+ polymorphism may be considered as a possible candidate marker for increased heat tolerance.

Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline.

Spermatogenic cells are susceptible to heat stress and undergo apoptosis. Although a variety of factors appear to be involved in the apoptotic process, the nature of the intracellular signaling pathway is ambiguous. To clarify the process, we chose a simple model in which testes of mice were exposed to mild heating by immersion in hot water at 42 degrees C for 15 min. In situ DNA fragmentation was detected by a TUNEL method. The release of cytochrome c into the cytoplasm was observed by Western blotting both in heat-treated testis and in isolated spermatogenic cells that had been incubated at 42 degrees C for 1h, but not in Sertoli cells. Minocycline, a semisynthetic tetracycline, is known to reach the brain by permeating the blood-brain barrier and suppresses apoptosis in neuronal cells. Since the testis also has a similar barrier, minocycline was examined as a possible agent to inhibit heat stress-induced apoptosis. The results indicate that minocycline suppressed the release of cytochrome c from mitochondria both in vivo and in vitro and significantly decreased the number of TUNEL-positive cells. These findings suggest that heat stress of testes triggers the release of cytochrome c from mitochondria in spermatogenic cells, leading to the activation of an apoptotic pathway.

Caspase activation contributes to delayed death of heat-stressed striatal neurons.

Hyperthermia can contribute to brain damage both during development and post-natally. We used rat embryonic striatal neurons in culture to study mechanisms underlying hyperthermia-induced neuronal death. Heat stress at 43 degrees C for 2 h produced no obvious signs of damage during the first 12 h after the stress, but more than 50% of the neurons died during the next 3 days. More than 40% of the neurons had activated caspases 24 h following the heat stress. Caspase-3 activity increased with a delay of more than 10 h following cessation of the heat stress, reaching a peak at approximately 18 h. Neuronal death measured 1-3 days after the stress was reduced by the general caspase inhibitors qVD-OPH (10-20 microm) and zVAD-fmk (50-100 microm). These inhibitors were protective even when added 9 h after cessation of the heat stress, consistent with the delayed activation of caspases. In contrast, blockers of Na+ channels and ionotropic glutamate receptors did not reduce the heat-induced death, indicating that glutamate excitotoxicity was not required for this neuronal death. These results show that the neuronal death produced by heat stress has characteristics of apoptosis, and that caspase inhibitors can delay this death.

Herbimycin A attenuates apoptosis during heat stress in rats.

Expression of heat shock proteins (HSPs) as a heat stress response is associated with acquisition of thermotolerance. Herbimycin A is a tyrosine kinase inhibitor that has been shown to induce HSPs. The present study aims to investigate the effects of herbimycin A on thermotolerance in rats subjected to heat stress exposure. Herbimycin A induced hsp70 to peak levels 12 h post-injection in rats without heat stress. No change in hsp70 levels was observed in the vehicle- and saline-treated rats. In rats exposed to heat stress at 45 degrees C for 25 min, 12 h post-treatment, lower peak temperatures were attained in herbimycin A-treated group as compared to the vehicle- and saline-treated groups. Terminal transferase-mediated d-UTP nick end labeling (TUNEL) showed that a significant decrease in apoptosis of hepatocytes in herbimycin A-treated rats as compared to the vehicle- and saline-treated rats. Caspase-3 activation was also lower in herbimycin A-treated rats, compared to the vehicle- and saline-treated rats. The present study has demonstrated that herbimycin A is effective for development of thermotolerance and therefore protects rats from heat stress.

Stress response in a juvenile hormone-deficient Drosophila melanogaster mutant apterous56f.

The apterous56f (ap56f) mutation leads to increases in juvenile hormone (JH) degradation levels and JH-esterase makes a greater contribution to the increase than JH-epoxide hydrolase. Dopamine levels in ap56f females, but not males, are higher than in wild-type. JH treatment of ap56f and wild-type females decreases their dopamine levels. ap56f females, but not males, produce less progeny. Survival under heat stress is dramatically decreased in ap56f females, but not males. ap56f flies show a stress reaction, as judged by changes in tyrosine decarboxylase and JH-hydrolysing activities, dopamine levels and fertility, but its intensity in the mutant females, but not males, differs significantly from wild-type. Thus, the ap56f mutation causes dramatic changes in female, but not male, metabolism and fitness.

EGF-dependent and independent activation of MAP kinase during Drosophila oogenesis.

Receptor tyrosine kinase (RTK) signaling is involved in multiple cell fate determination during Drosophila oogenesis. To address the problem of signaling specificity, we sought to systematically document the expression pattern of activated MAP kinase, the downstream effector of RTK signaling. We show that MAP kinase is activated in some of the cell types in which Drosophila EGF receptor signaling is known to function. MAP kinase activation is also associated with many cell migration events. Finally, MAP kinase is activated by heat stress without altering follicle cell fates. The implications of these findings are discussed.

Hepatic tyrosine aminotransferase activity is affected by chronic heat stress and dietary tyrosine in broiler chickens.

1. Two experiments were conducted to investigate the impact of high temperature and dietary tyrosine (Tyr) content on performance and activity of hepatic tyrosine aminotransferase (EC 2.6.1.5.), an enzyme that catalyses the first step in the metabolic degradation of Tyr in broiler chickens. 2. Two-week-old birds were allocated to one of three temperature treatments: 24 degrees C (control), 36 degrees C (heat stress, HS) and 24 degrees C pair-fed (24PF) for 2 weeks and fed on diets containing 100% (Experiment 1) and 50, 100 and 200% (Experiment 2) of the NRC requirement for Tyr. 3. In Experiment 1, exposure of chickens to 36 degrees C for 2 weeks caused significant increase in hepatic tyrosine aminotransferase activity but no significant change in activity of hepatic phenylalanine 4-hydroxylase (EC 1.14.16.1) (an enzyme that catalyses conversion of phenylalanine to Tyr) compared with the 24PF birds. No significant changes attributable to heat stress were detected in hepatic glutamic-oxaloacetic transaminase (EC 2.6.1.1) activity. 4. In Experiment 2, heat stress caused reductions in weight gain and feed intake in chickens on all diets, compared with their control counterparts. Hepatic tyrosine aminotransferase activity was increased by heat stress compared with their 24PF counterparts in chickens fed on the 100 and 200% Tyr diets, while in chickens fed the 50% Tyr diet, it was reduced by heat stress. 5. From these results, it is suggested that hepatic tyrosine aminotransferase activity is affected by heat stress and dietary Tyr content and the increased tyrosine aminotransferase activity with, in part, relatively low phenylalanine hydroxylase activity in hepatic tissues may be involved in the Tyr metabolism characteristic of heat-stressed chickens.

The effect of heat stress on the induced hepatic drug metabolizing system in rats.

The activity of the hepatic oxidative drug metabolizing system has been investigated in an experimentally-induced heat stress animal model pretreated with phenobarbitone. Female rats, unacclimatized and untrained were pretreated for 3 days with phenobarbitone as the inducing agent for the drug metabolizing systems. On the fourth day, they were restrained and exposed to an ambient temperature of 40 degrees C. One hour after acute exposures to such conditions, the activities of hepatic cytochrome P450, cytochrome b5 and NADPH cytochrome c reductase were significantly decreased in the induced animal model. Further, cytochrome P450 isozymes observed by SDS-gel electrophoresis were significantly decreased. In addition, the hypnotic effect of pentobarbitone was significantly increased. It is concluded that the activity of the hepatic oxidative drug metabolizing enzymes was decreased in induced drug metabolism systems exposed to heat stress conditions.