RESUMO
Study objectives were to determine the effects of mitoquinol (MitoQ, a mitochondrial-targeted antioxidant) on biomarkers of metabolism and inflammation during acute heat stress (HS). Crossbred barrows [nâ =â 32; 59.0â ±â 5.6 kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (nâ =â 8; TNCon), 2) TN and MitoQ (nâ =â 8; TNMitoQ), 3) HS control (nâ =â 8; HSCon), or 4) HS and MitoQ (nâ =â 8; HSMitoQ). Pigs were acclimated for 6 d to individual pens before study initiation. The trial consisted of two experimental periods (P). During P1 (2 d), pigs were fed ad libitum and housed in TN conditions (20.6â ±â 0.8 °C). During P2 (24 h), HSCon and HSMitoQ pigs were exposed to continuous HS (35.2â ±â 0.2 °C), while TNCon and TNMitoQ remained in TN conditions. MitoQ (40 mg/d) was orally administered twice daily (0700 and 1800 hours) during P1 and P2. Pigs exposed to HS had increased rectal temperature, skin temperature, and respiration rate (+1.5 °C, +6.8 °C, and +101 breaths per minute, respectively; Pâ <â 0.01) compared to their TN counterparts. Acute HS markedly decreased feed intake (FI; 67%; Pâ <â 0.01); however, FI tended to be increased in HSMitoQ relative to HSCon pigs (1.5 kg vs. 0.9 kg, respectively; Pâ =â 0.08). Heat-stressed pigs lost BW compared to their TN counterparts (-4.7 kg vs. +1.6 kg, respectively; Pâ <â 0.01); however, the reduction in BW was attenuated in HSMitoQ compared to HSCon pigs (-3.9 kg vs. -5.5 kg, respectively; Pâ <â 0.01). Total gastrointestinal tract weight (empty tissue and luminal contents) was decreased in HS pigs relative to their TN counterparts (6.2 kg vs. 8.6 kg, respectively; Pâ <â 0.01). Blood glucose increased in HSMitoQ relative to HSCon pigs (15%; Pâ =â 0.04). Circulating non-esterified fatty acids (NEFA) increased in HS compared to TN pigs (Pâ <â 0.01), although this difference was disproportionately influenced by elevated NEFA in HSCon relative to HSMitoQ pigs (251 µEq/L vs. 142 µEq/L; Pâ <â 0.01). Heat-stressed pigs had decreased circulating insulin relative to their TN counterparts (47%; Pâ =â 0.04); however, the insulin:FI ratio tended to increase in HS relative to TN pigs (Pâ =â 0.09). Overall, circulating leukocytes were similar across treatments (Pâ >â 0.10). Plasma C-reactive protein remained similar among treatments; however, haptoglobin increased in HS relative to TN pigs (48%; Pâ =â 0.03). In conclusion, acute HS exposure negatively altered animal performance, inflammation, and metabolism, which were partially ameliorated by MitoQ.
Heat stress (HS) compromises animal health and productivity, and this causes major economic losses in almost every livestock sector. The negative consequences of HS are thought to originate from intestinal barrier dysfunction and subsequent immune activation. The underlying causes of lost intestinal integrity during HS are likely multifactorial; however, intestinal ischemia, increased accumulation of reactive oxygen species, and the ensuing epithelial oxidative damage might be potential causes. Mitochondria-targeted antioxidants, such as mitoquinol (MitoQ), are probably more effective than traditional dietary antioxidants (i.e., selenium, vitamin E) at alleviating oxidative stress, as they localize and accumulate within the mitochondria, potentiating their antioxidant activity. Thus, the present study aimed to investigate MitoQ's role during a thermal event in growing pigs. Herein, HS increased all body temperature indices, decreased feed intake (FI), and induced substantial body weight (BW) loss. Interestingly, the reduction in FI and BW was less dramatic in pigs receiving MitoQ. Changes in circulating metabolism and the acute phase response were observed due to the HS challenge; however, contrary to our expectations, these changes were not offset by MitoQ administration. Although our results suggest a positive MitoQ effect on growth performance, future studies are needed to corroborate the replicability of this response during HS.
Assuntos
Ubiquinona , Animais , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/administração & dosagem , Masculino , Suínos , Compostos Organofosforados/farmacologia , Compostos Organofosforados/administração & dosagem , Antioxidantes/farmacologia , Temperatura Alta/efeitos adversos , Resposta ao Choque Térmico/efeitos dos fármacos , Doenças dos Suínos/tratamento farmacológico , Transtornos de Estresse por Calor/veterinária , Transtornos de Estresse por Calor/tratamento farmacológico , Distribuição Aleatória , Temperatura Corporal/efeitos dos fármacosRESUMO
The purpose of this investigation was to establish the role biological sex plays in circulating factors following heat stress (HS). Barrows and gilts (36.8â ±â 3.7 kg body weight) were kept in either thermoneutral (TN; 20.8â ±â 1.6 °C; 62.0%â ±â 4.7% relative humidity; nâ =â 8/sex) conditions or exposed to HS (39.4â ±â 0.6 °C; 33.7%â ±â 6.3% relative humidity) for either 1 (HS1; nâ =â 8/sex) or 7 (HS7; nâ =â 8/sex) d. Circulating glucose decreased as a main effect of the environment (Pâ =â 0.03). Circulating non-esterified fatty acid (NEFA) had an environmentâ ×â sex interaction (Pâ <â 0.01) as HS1 barrows had increased NEFA compared to HS1 gilts (Pâ =â 0.01) and NEFA from HS7 gilts increased compared to HS1 gilts (Pâ =â 0.02) and HS7 barrows (Pâ =â 0.04). Cortisol, insulin, glucagon, T3, and T4 were reduced as a main effect of environment (Pâ ≤â 0.01). Creatinine was increased in HS1 and HS7 animals compared to TN (Pâ ≤â 0.01), indicative of decreased glomerular filtration rate. White blood cell populations exhibited differential patterns based on sex and time. Neutrophils and lymphocytes had an environmentâ ×â sex interaction (Pâ ≤â 0.05) as circulating neutrophils were increased in HS1 barrows compared to TN and HS7 barrows, and HS1 gilts (Pâ ≤â 0.01) and HS7 barrows had less neutrophils compared to TN barrows (Pâ =â 0.01), whereas they remained similar in gilts. In contrast, barrow lymphocyte numbers were similar between groups, but in HS7 gilts they were decreased compared to TN and HS1 gilts (Pâ ≤â 0.04). In total, these data demonstrate that HS alters a host of circulating factors and that biological sex mediates, at least in part, the physiological response to HS.
Heat stress (HS) negatively impacts efficient pork production; however, the role of biological sex is largely unknown. The objective of this study was to determine the extent to which HS differentially impacted hematological parameters in barrows and gilts. To address this, 3-mo-old barrows and gilts were exposed to ambient temperature (TN) or constant HS for 1 or 7 d. Following the experimental period, blood was collected for analysis of hormones, metabolites, immune cells, and markers of organ damage. Overall, cortisol, insulin, glucagon, T3, and T4 were reduced following HS. Furthermore, 7 d of HS decreased circulating glucose, albeit slightly. Circulating fatty acids had a sex-specific response as HS1 barrows and HS7 gilts were increased compared to their environmental counterparts, though, these changes are minor compared to those expected with a similar feed restriction. HS caused immune system activation in barrows and gilts; however, circulating levels of specific white blood cells were time- and sex-dependent. Barrows appeared more resistant to HS-mediated kidney injury acutely; however, with continued heating, markers of kidney injury were similar between barrows and gilts. In total, these data suggest biological sex regulates some, but not all, aspects of HS-mediated biological changes in pigs.
Assuntos
Ácidos Graxos não Esterificados , Animais , Feminino , Masculino , Suínos/fisiologia , Ácidos Graxos não Esterificados/sangue , Temperatura Alta/efeitos adversos , Fatores Sexuais , Glicemia , Resposta ao Choque TérmicoRESUMO
Oxidative stress contributes to heat stress (HS)-mediated alterations in skeletal muscle; however, the extent to which biological sex mediates oxidative stress during HS remains unknown. We hypothesized muscle from males would be more resistant to oxidative stress caused by HS than muscle from females. To address this, male and female pigs were housed in thermoneutral conditions (TN; 20.8 ± 1.6°C; 62.0 ± 4.7% relative humidity; n = 8/sex) or subjected to HS (39.4 ± 0.6°C; 33.7 ± 6.3% relative humidity) for 1 (HS1; n = 8/sex) or 7 days (HS7; n = 8/sex) followed by collection of the oxidative portion of the semitendinosus. Although HS increased muscle temperature, by 7 days, muscle from heat-stressed females was cooler than muscle from heat-stressed males (0.3°C; P < 0.05). Relative protein abundance of 4-hydroxynonenal (4-HNE)-modified proteins increased in HS1 females compared with TN (P = 0.05). Furthermore, malondialdehyde (MDA)-modified proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration, a DNA damage marker, was increased in HS7 females compared with TN females (P = 0.05). Enzymatic activities of catalase and superoxide dismutase (SOD) remained similar between groups; however, glutathione peroxidase (GPX) activity decreased in HS7 females compared with TN and HS1 females (P ≤ 0.03) and HS7 males (P = 0.02). Notably, HS increased skeletal muscle Ca2+ deposition (P = 0.05) and was greater in HS1 females compared with TN females (P < 0.05). Heat stress increased sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2a protein abundance (P < 0.01); however, Ca2+ ATPase activity remained similar between groups. Overall, despite having lower muscle temperature, muscle from heat-stressed females had increased markers of oxidative stress and calcium deposition than muscle from males following identical environmental exposure.NEW & NOTEWORTHY Heat stress is a global threat to human health and agricultural production. We demonstrated that following 7 days of heat stress, skeletal muscle from females was more susceptible to oxidative stress than muscle from males in a porcine model, despite cooler muscle temperatures. The vulnerability to heat stress-induced oxidative stress in females may be driven, at least in part, by decreased antioxidant capacity and calcium dysregulation.