RESUMO

Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator-activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty-three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2-methyl-2-phenoxy-propionic acid; 10 mg/kg of 2-methyl-2-phenoxy-propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum ß-hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2-methyl-2-phenoxy-propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2-methyl-2-phenoxy-propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.

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RESUMO

BACKGROUND: Ovine pregnancy toxaemia is a common metabolic disorder of ewes due to increased foetal energy requirements in late pregnancy. This pathology is a metabolic condition characterized by hypoglycaemia and hyperketonaemia resulting in the inability of the animal to maintain an adequate energy balance. The response to treatment is effective, if it is started in the early stages of the disease, when irreversible neurological injuries have not yet been established. The aim was to evaluate three therapeutic alternatives to effectively reverse the disease process in its early stages. For this, thirty adult Corriedale ewes, pregnant with a single lamb, were randomly separated in three groups of ten animals each, at day 130 of gestation. From that day onwards, ewes were locked up for forage fasting until glycaemia reached clinical values defining sub-clinical pregnancy toxaemia (1.59 ± 0.24 mmol/L). After fasting, ewes grazed and received a treatment for 4 days: 50 ml i.v. infusions of hypertonic glucose and 20 UI insulin/ewe/day s.c. or 100 ml/sheep/12 h of glycerol together with propylene glycol oral solution or fed with pasture supplemented with two daily intakes 300 g/sheep of cracked corn. Glycaemia and ß-hydroxybutyrate were determined in all the animals from the beginning of fasting until the completion of the treatment. RESULTS: Fasting caused a decline in blood glucose in the 3 groups. This decline continued until fasting was withdrawn and treatment began. Thereafter blood glucose increased in all three groups, although in the group supplemented with glycerol and propylene glycol it started to increase significantly after 12 h. The values of ß-hydroxybutyrate decreased in the 3 groups at the start of treatment, and this decline was more pronounced earlier on and in the group supplemented with glycerol and propylene glycol. We found no significant differences between all experimental groups. No animal showed clinical signs of pregnancy toxaemia throughout the research. CONCLUSIONS: The three treatments administered to sheep affected by sub-clinical pregnancy toxaemia were able to restore normal concentration of glucose and ß-hydroxybutyrate in blood, although per os administration of 100 ml/sheep/12 h of glycerol with propylene glycol, was the most successful treatment, normalizing the aforementioned biochemical parameters in a shorter time.

RESUMO

AIM: To detect early changes in the metabolic profile of pregnant ewes subject to acute feed restriction at 130 days of gestation, and to establish indicators of risk for ovine pregnancy toxaemia (OPT) for diagnostic purposes. METHODS: Twenty Corriedale ewes with known mating dates, carrying a single fetus, were used. Ewes were maintained on meadow grasslands and at 130 days of gestation were randomly divided in two groups of 10 ewes. The control group had ad libitum access to pasture. Ewes in the restricted group were subjected to an acute feed restriction for a maximum of 144 hours (6 days), with free access to water. From the start (0 hours) until the end of feed restriction, blood samples were collected from all ewes to monitor concentrations of cortisol, non-esterified fatty acids (NEFA), ß-hydroxybutyrate (BOHB) daily, and glucose in plasma every 6 hours; urinary pH was also measured. Every 6 hours the food restricted ewes were observed to detect clinical signs of OPT e.g. apathy, grinding teeth, empty chewing movements, head leaning against the wall, tachypnea and not drinking water. RESULTS: In food-restricted ewes, concentrations of glucose decreased and differed from control ewes from 54 to 90 hours (p<0.001), and 96 to 102 hours (p<0.05). Concentrations of BOHB, cortisol and NEFA increased following feed restriction and differed from control ewes after 48 to 144 hours (p<0.01). Eight of the 10 restricted ewes showed clinical signs of OPT after 102-132 hours. Mean concentrations of glucose, BOHB and cortisol differed between control and restricted ewes prior to the onset of clinical signs of OPT, after 48-96 hours of feed restriction (p<0.01). Mean gestational length, and time from birth to placental expulsion was not affected by the feed restriction. CONCLUSIONS: Our results suggest that concentrations of glucose, BOHB and cortisol in plasma may provide a precocious diagnosis of subclinical OPT, using values of 1.59 (SD 0.24) mmol/L, 2.26 (SD 1.03) mmol/L and 15.09 (SD 7.75) nmol/L, respectively. The identification of a potentially harmful metabolic imbalance could lead to the improvement of treatment success.

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RESUMO

The histological changes of the liver in ewes with pregnancy toxemia were characterized. Ten ewes were fed on grass ad libitum, and another ten were starved from day 130 of pregnancy for up to four days. Liver puncture biopsies were performed at days 70, 100, 130, and 140 of pregnancy, and at day 45 in postpartum. Seric hydroxybutyrate (HB), non-esterified fatty acids (NEFA), aspartate aminotransferase, and alkaline phosphatase were dosed. Histological preparations revealed similar incidence and intensity of mild liver steatosis in both groups at day 130. Starved ewes become toxemic (as indicated by HB), and at day 140 exhibited more severe injury in a higher proportion (9/9 vs. 4/10; P<0.01). Almost all of them (7/9) had large amounts of small lipid droplets in almost every hepatocyte over the whole liver acinus, and higher NEFA values. At day 45 in postpartum, both groups had mild steatotic changes as initially. A positive correlation between severity of liver damage seric and only aspartate aminotransferase was observed at day 140 in starved animals (P<0.05). This enzyme could be used to assess liver damage, but not alkaline phosphatase. All samples with degeneration corresponded to the microvesicular type. A short starvation period during late pregnancy in ewes produced reversible liver degeneration.(AU)

Caraterizaram-se histologicamente as alterações do fígado de ovelhas com toxemia da prenhez. Dez ovelhas foram mantidas em pasto ad libitum, e outras 10 submetidas a jejum a partir do 130º dia de gestação, por até quatro dias. Biopsias hepáticas foram realizadas aos 70, 100, 130 e 140 dias de gestação e, aos 45 dias pós-parto. Níveis séricos de hydroxibutirato, ácidos graxos não esterificados (NEFA), aspartato aminotransferase e fosfatase alcalina foram determinados. O estudo histológico revelou extensão semelhantes de degeneração nos dois grupos no 130º dia de gestação. No 140º dia de gestação, alta proporção de animais submetidos ao jejum, apresentou intensa degeneração no fígado (9/9 vs. 4/10; P<0,01) e, desses, quase todos 7/9 tinham grande quantidade de pequenas gotas de lipídios em quase todos os hepatócitos, nas diferentes regiões do ácino, além de níveis séricos mais elevados de NEFA. Quarenta e cinco dias pós-parto, os animais dos dois grupos apresentaram degeneração discreta, como no início. No 140º dia de gestação, verificou-se correlação positiva entre a severidade das lesões histológicas e a enzima aspartato aminotransferase, nos animais submetidos a jejum (P<0.05). Todas as amostras com degeneração corresponderam ao tipo microvesicular. Um curto período de jejum, na fase final da gestação da ovelha produz degeneração hepática reversível.(AU)

Assuntos

RESUMO

The histological changes of the liver in ewes with pregnancy toxemia were characterized. Ten ewes were fed on grass ad libitum, and another ten were starved from day 130 of pregnancy for up to four days. Liver puncture biopsies were performed at days 70, 100, 130, and 140 of pregnancy, and at day 45 in postpartum. Seric hydroxybutyrate (HB), non-esterified fatty acids (NEFA), aspartate aminotransferase, and alkaline phosphatase were dosed. Histological preparations revealed similar incidence and intensity of mild liver steatosis in both groups at day 130. Starved ewes become toxemic (as indicated by HB), and at day 140 exhibited more severe injury in a higher proportion (9/9 vs. 4/10; P<0.01). Almost all of them (7/9) had large amounts of small lipid droplets in almost every hepatocyte over the whole liver acinus, and higher NEFA values. At day 45 in postpartum, both groups had mild steatotic changes as initially. A positive correlation between severity of liver damage seric and only aspartate aminotransferase was observed at day 140 in starved animals (P<0.05). This enzyme could be used to assess liver damage, but not alkaline phosphatase. All samples with degeneration corresponded to the microvesicular type. A short starvation period during late pregnancy in ewes produced reversible liver degeneration.

Caraterizaram-se histologicamente as alterações do fígado de ovelhas com toxemia da prenhez. Dez ovelhas foram mantidas em pasto ad libitum, e outras 10 submetidas a jejum a partir do 130º dia de gestação, por até quatro dias. Biopsias hepáticas foram realizadas aos 70, 100, 130 e 140 dias de gestação e, aos 45 dias pós-parto. Níveis séricos de hydroxibutirato, ácidos graxos não esterificados (NEFA), aspartato aminotransferase e fosfatase alcalina foram determinados. O estudo histológico revelou extensão semelhantes de degeneração nos dois grupos no 130º dia de gestação. No 140º dia de gestação, alta proporção de animais submetidos ao jejum, apresentou intensa degeneração no fígado (9/9 vs. 4/10; P<0,01) e, desses, quase todos 7/9 tinham grande quantidade de pequenas gotas de lipídios em quase todos os hepatócitos, nas diferentes regiões do ácino, além de níveis séricos mais elevados de NEFA. Quarenta e cinco dias pós-parto, os animais dos dois grupos apresentaram degeneração discreta, como no início. No 140º dia de gestação, verificou-se correlação positiva entre a severidade das lesões histológicas e a enzima aspartato aminotransferase, nos animais submetidos a jejum (P<0.05). Todas as amostras com degeneração corresponderam ao tipo microvesicular. Um curto período de jejum, na fase final da gestação da ovelha produz degeneração hepática reversível.

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