Nessun titolo diapositiva

1
(No Transcript)
2
DAIRY COWS
Dairy cows, especially in the postpartum period,
are subjected to many conditions that can alter
their metabolic equilibrium and detoxifying
processes

• Energy deficit
• Liver dysfunctions
• Ammonia intoxication
• Oxydative stress

3
ENERGY DEFICIT DURING EARLY LACTATION
HIGH PRODUCTION-RELATED LOSSES
4
METABOLIC DISEASES
During early lactation, the amount of energy
required for maintenance and milk production
exceeds the amount of energy the cow can obtain
from dietary sources
To meet their energy requirements during the
first weeks of lactation, dairy cows mobilize
large quantities of fatty acids from adipose
tissue, resulting in increased circulating
concentrations of NEFA (Non Esterified Fatty
Acidc)
5
METABOLIC DISEASES
In the liver the NEFA are oxidized or esterified
into triglycerides which are exported in VLDL
(Very Low Density Lipoproteins Low level of
synthesis in ruminants) or accumulated in the
hepatic tissue
If mobilization of fatty acids from adipose
tissue is excessive, the capacity of the liver to
either export or oxidize fatty acids is exceeded
STEATOSIS Accumulation of fatty acids as
triglycerides in the liver
KETOSIS Partial oxidation of
fatty acids and formation of ketone bodies
6
RUMINANT KETOSIS
Final 1/3 of pregnancy in ovines
Puerperium in cows
Pathological states
Considerable energy requirement
Anorexia
Energy deficit
7
RUMINANT KETOSIS
Utilisation of fats
Hypoglycemia
Excessive formation of acetate
Lowered sugar reserves
Energy deficit
Ketone bodies
8
HEPATIC STEATOSIS Fat cow syndrome
Cattle in an excellent nutritional state
Energy deficiency
Mobilisation of large quantities of fats from
lipid reserves
Hepatic stress
Accumulation of fats in hepatocytes
9
METABOLIC DISEASES

• The results of the negative energy balance and
  the following metabolic impairment are
• Decreased feed intake
• Decreased ureagenic and glucogenic capacity of
  the liver
• Decreased milk production
• Impairment of defence mechanisms
• Increased incidence of disease
  (Dystocya, retained fetal membranes, metritis,
  diplaced abomasum, mastitis)
• Decreased reproductive performance

10
THE LIVER
The liver is the hardest working organ of the
body with hundreds of tasks to perform
The liver is the most important organ in
detoxification
At the centre of all the metabolic processes
which take place in the organism
Its functions are interrelated with the
metabolism of all organs and tissues
11
LIVER FUNCTIONS

• Metabolism
• Hormones
• Vitamins

• Metabolism
• Carbohydrate
• Fat
• Protein

Synthesis and secretion of bile
Storage of liposoluble vitamins
Synthesis of plasma proteins
Detoxification
Synthesis of clotting factors and fibrinolytics
Energy reserve (glycogen)
12
ALTERATIONS IN HEPATIC FUNCTION
Ketosis Hepatic steatosis Intoxication
Infectious diseases Incorrect nutrition
Metabolic dysfunction in general
Alterations in hepatic function
Repercussions throughout the organism

• Deterioration in the state of health
• Impairment of defence mechanisms
• Lowering of detoxifying capacity
• Alterations in hormonal metabolism and
  hypofertility
• Lowering of productive capacity
  (qualitative-quantitative changes in milk)

13
AMMONIA
In ruminants ammonia is produced during the
degradation of proteins in the rumen and in the
catabolism of amino acids in tissues
In ruminants, hyperammoniemia is often associated
with high non-protein nitrogen feeding and
nitrogen absobed as ammonia can be several times
the amount absorbed in the form of amino acids or
peptides
Ammonia intoxication can also results from
metabolic disorders, which affects liver
detoxifying capacities, or from other hepatic
dysfunctions
All cows after calving have increased circulating
ammonia because of decreased ureagenesis caused
by hepatic lipid accumulation
14
AMMONIA
Ammonia is removed from the blood by the
liver The liver converts the ammonia to urea
which is released in the blood

• Urea in the blood can follow two routes
• It can return to the rumen through the saliva
• It can be excreted into the urine by the kidneys

There are also extrahepatic detoxifying pathways
of ammonia which use Aspartic and Glutamic acids
15
AMMONIA INTOXICATION

• Rations low in digestible energy
• Urea fed at high levels
• Excessive or highly degradable protein in the
  diet

• Ketosis
• Steatosis
• Intoxications
• Infectious diseases

Not all the ammonia produced in the rumen can be
converted to microbial protein
Decreased liver detoxifying capacity
AMMONIA INTOXICATION
16
AMMONIA INTOXICATION
Ammonia decreases the ability of hepatocytes to
synthesize glucose from propionate and affect
intermediary metabolism. Excess of ammonia is
very toxic to cells and affects eggs and embryos
and lower fertility

• Increases the incidence of metabolic disorders
• Reduces milk production
• Impairs reproductive performance

AMMONIA
17
OXYDATIVE STRESS
Metabolic processes, environmental insults and
inflammatory responses produce compounds called
reactive oxygen species or free radicals
Free radicals are reactive molecules that can be
very toxic to tissues

• Oxidative stress is most problematic in dairy
  cow
• High metabolism
• High energy rations
• Diets high in aflatoxins

18
OXYDATIVE STRESS
Oxidative stress is very detrimental to animal
health and herd productivity

• Reduced reproductive efficiency
• Decreased immune function
• Increased susceptibility to
• Mastitis
• Retained placenta
• Metritis

19
LA SOLUCIÓN EN SOLUCIÓN

• Metabolic disorders
• Liver dysfunctions
• Ammonia intoxication
• Oxidative stress

20
METABOLASE
Detoxifying, antioxidant and tonic preparation
indicated for use in all animals subjected to
heavy and/or protracted physical activity
(high producing cows, sport, work,
convalescence, etc.), regulating protein,
carbohydrate and lipid metabolism and
reactivating hepatocyte and muscle cells
21
METABOLASE
The components selected are activators for
important metabolic pathways which, following
situations of toxicosis, fatigue or stress, may
be inhibited or may not adequately break down and
eliminate the products of catabolism
22
METABOLASE
Owing to the completeness and synergism of its
active substances, it carries out a broad-scale
action on the biochemical processes of various
organs It detoxifies the organism and permits
recovery of the organs most affected, rapidly
and efficaciously reactivating metabolic function
23
THE ACTIVE SUBSTANCES

• VITAMINS
• L-Carnitine
• Lipoic/Thioctic acid
• Vitamin B6
• Vitamin B12

• AMINO ACIDS
• Acetylmethionine
• L-Ornithine,
• L-Arginine,
• L-Citrulline
• L-Lysine
• Glycine,
• Aspartic acid,
• Glutamic acid
• Taurine

• SUGARS
• Fructose
• Sorbitol

24
THE ACTIVE SUBSTANCES

• Anti-ketogenic anti-steatogenic and
  gluconeogenic activity
• Carnitine
• Vitamin B6
• Vitamin B12
• Methionine
• L-Lysine
• Lipoic/Thioctic acid

• Improvement of liver synthesis and detoxifying
  processes
• Methionine
• L-Lysine
• Vitamin B6
• Vitamin B12
• Lipoic/Thioctic acid

• Energising action
• Fructose
• Sorbitol

• Ammonia detoxification
• L-Ornithine,
• L-Citrulline,
• L-Arginine
• Aspartic acid
• Glutamic acid

• Antioxidant activity
• Lipoic/Thioctic acid

• Biligenic activity
• Glycine Taurine

25
L - CARNITINE

• Exogenous intake with the diet
• Endogenous synthesis by Lysine and Methionine

Found particularly in organs and tissues (liver,
muscle, heart) which show a marked capacity to
use fats as an energy source
ESSENTIAL FOR THE TRANSFORMATION OF FATS INTO
ENERGY
26
TRANSFORMATION OF FATS INTO ENERGY
Trasformation of fats into energy takes place in
mithocondria
Mitochondria are the power generators of the cell
They convert oxygen and nutrients into ATP
(adenosine triphosphate)
ATP is the chemical energy "currency" of the cell
that powers the cell's metabolic activities
27
L - CARNITINE

• TWO ESSENTIAL FUNCTIONS
• The only physiological carrier for transport of
  fatty acids inside the mitochondria where they
  are burnt to produce energy (?-oxidation)
• It removes from the mitochondria the acetyl
  groups which are formed by lipid and amino-acid
  metabolism

28
FATTY ACID TRANSPORT INTO THE MITOCHONDRIA
The oxidation of fatty acids is an important
source of energy for ATP production in
mitochondria
Fatty acids are oxidized inside the mitochondrial
matrix but the fatty acids to be oxidized come
from the cytosol
Fatty acids are activated in the cytosol by
esterification with Coenzyme A (CoA) to form a
fatty acid-CoA complex
Fatty acid-CoA is impermeable to the inner
mitochondrial membrane and needs carnitine to
enter
29
FATTY ACID TRANSPORT INTO THE MITOCHONDRIA
The transport of fatty acids into mitochondria is
accomplished by the carnitine palmitoyl-transferas
e system (CPTI and CPTII)
CPTI exchanges carnitine for the CoA attached to
long chain fatty acids to form a fatty
acid-carnitine conjugate The fatty acid-carnitine
is transported into the matrix by a transporter
protein in the inner mitochondrial membrane Once
the fatty acid-carnitine is inside the matrix,
CPTII exchanges CoA for carnitine to produce
fatty acid-CoA once again, ready to enter fatty
acid beta-oxidation to produce energy
30
BETA-OXIDATION

• Beta-oxidation is the process by which the fatty
  acyl CoA is degraded
• The products of beta-oxidation are
• acetyl CoA
• FADH2, NADH and H

Acetyl CoA is oxidated by the Krebs cycle to CO2
and H2O In liver acetyl CoA may be used for
ketone body synthesis FADH2 and NADH H are
oxidized by the mitochondrial electron transport
system, yielding ATP
31
THERAPEUTIC ACTIVITY OF L-CARNITINE

• It prevents accumulation of fatty acids in
  tissues (ANTI-STEATOGENIC ACTION)
• It removes acetyl groups, avoiding the formation
  of ketone bodies (ANTI-KETOGENIC ACTION)
• It improves muscular function and resistance to
  effort and shortens recovery times
  (PHYSICAL RECUPERATION ACTIVITY)
• It favours the contractile activity of cardiac
  muscle and increases coronary flow

32
DEFICIENCY OF L-CARNITINE
Blockage of ?-oxidation of fatty acids
Accumulation of free fatty acids in cells
Reduction in energy supply to cells
Toxic effects on cells
KETOSIS HEPATIC STEATOSIS MUSCULAR
ASTHENIA MUSCULAR ATONY CARDIAC INSUFFICIENCY
33
METHIONINE

• Methionine is an essential amino acid
• A critical component of tissue development,
  growth and tissue repair
• It is indispensable to maintain liver function
• It is the only amino acid containing a thioether
  group, essential for hepatic detoxification and
  synthesis processes
• Precursor of SAM (S-adenosylmethionine), the
  universal methyl donor for over 100 reactions

34
METHIONINE

• It acts as a lipotropic agent to prevent excess
  fat build-up in the liver
• Essential for the absorption and transportation
  and bio-availability of selenium and zinc
• An excellent chelator of heavy metals
• Indispensable for synthesis of milk casein
• Intervenes in hepatic synthesis of plasma
  albumins and globulins (antibodies)
• It reduces histamine release
• Intervenes in the synthesis of choline,
  carnitine, glutathione and membrane phospholipids

35
METHIONINE
As "methyl donor", methionine contributes to the
formation of numerous important compounds
Methyl Group
Thioether group
Essential for hepatic detoxification and
synthesis processes
Amino- Propylic Group
Protein synthesis (Antibodies, enzymes, casein)
COOH
36
L-LYSINE

• An essential amino acid
• Intervenes in various metabolic processes,
  amongst which biosynthesis (acting with
  methionine) of endogenous L-carnitine in the liver

Lysine
Methionine
L-CARNITINE
37
LIPOIC or THIOCTIC ACID
Because of its myriad biological activities
against oxidative stress it is considered to be
the ideal antioxidant
Lipoic acid also intervenes in detoxification
processes and numerous biochemical reactions
regarding carbohydrate, lipid and amino-acid
metabolism
Passing from the disulfhydryl to the disulphide
form and vice-versa, it is an efficient
oxidation-reduction system
Antioxidant activity
38
LIPOIC/THIOCTIC ACID The Ideal
Antioxidant

• Unique in its ability to act as an antioxidant
  both in fat- and water-soluble tissues
• It can utilize the power of the cells own
  metabolic processes for its recycling (Metabolic
  antioxidant)
• It scavanges most reactive oxygen species
• It is capable of regenerating vitamin C, vitamin
  E and glutathione
• It has a metal chelating activity

39
LIPOIC/THIOCTIC ACID
By means of its sulfhydryl groups, it can block
toxic substances which inactivate enzymes and
proteins
Toxic substance
Blocked toxic substance
40
LIPOIC/THIOCTIC ACID
Donating sulfhydryl groups, it reactivates
enzymes and proteins altered by toxic substances
Inactivated enzyme
Reactivated enzyme
41
LIPOIC/THIOCTIC ACID

• THERAPEUTIC ACTIVITY
• Antioxidant
• Detoxifying
• Lipotropic
• Anti-steatogenic

42
VITAMIN B6

• Water-soluble vitamin
• It has an important role as coenzyme
• in protein metabolism reactions
• It is an indispensable regulator of
• metabolism at the level of the liver,
• nervous system, skin and haematopoietic
• system

43
VITAMIN B12

• Nucleic acid synthesis (DNA/RNA)
• Protein synthesis
• Synthesis of VLDL (Very low density
  lipoproteins), preventing hepatic steatosis
• Synthesis of methionine, homocysteine and
  choline (lipotropic factors with liver-protectant
  and anti-steatogenic actions)
• Transformation of propionic acid into glucose
  (in cattle)
• Red blood cell production

INDISPENSABLE FACTOR IN ALL TROPHIC AND GROWTH
PROCESSES
44
METABOLASEDetoxifying action on ammonia

• L-Ornithine
• L-Citrulline
• L-Arginine
• Aspartic acid
• Glutamic acid

45
L-ORNITHINE L-CITRULLINE L-ARGININE

• Amino acids which are indispensable for
  metabolism of ammonia
• Ammonia is an end product of nitrogen catabolism,
  very toxic to the organism
• Through hepatic ureogenesis (Urea Cycle), ammonia
  is transformed into the less toxic compound urea,
  which is eliminated with the urine

46
UREOGENESIS
AMMONIA
Aspartic acid
Citrulline
Ureogenesis takes place in the liver and is
essential for ammonia detoxification
UREA CYCLE
Arginine
Ornithine
UREA
The urea cycle is particularly important for
ruminants as ammonia is produced in high
quantities during fermentation of nitrogenous
matter in the rumen
47
ASPARTIC ACID

• Intervenes in the urea cycle as supplier of an
  amine group
• It participates in detoxification of ammonia in
  the organism through asparagine synthesis
  (extrahepatic detoxification of ammonia)
• By means of deamination, it gives rise to
  oxaloacetate which permits catabolism of
  acetyl-CoA in the Krebs cycle, indirectly
  inhibiting ketogenesis

48
ASPARTIC ACID
Asparagine represents a form of transport for
ammonia
In the kidney, asparagine is split into aspartic
acid and ammonia which is then eliminated with
the urine in the form of ammonium ions
(Extrahepatic detoxification of ammonia)
ASPARTIC ACID AMMONIA
ASPARAGINE
49
GLUTAMIC ACID
A prominent intermediate in ammonia elimination
as well as in anabolic pathways
Together with aspartic acid, participates in
detoxification of ammonia in extrahepatic
tissues, favouring renal elimination of ammonia
GLUTAMIC ACID AMMONIA
GLUTAMINE
Glutamine supplies the nitrogen necessary for
biosynthesis of various compounds amino acids,
purine and pyrimidine, folic acid, aminosugars
50
AMMONIA
Extrahepatic detoxification of ammonia
Hepatic detoxification of ammonia
Citrulline
Ornithine
Aspartic acid
UREA CYCLE
Glutamic acid
Asparagine Glutamine
Arginine
UREA
AMMONIA
URINE
51
METABOLASE Biligenic action

• Glycine
• Taurine

52
GLYCINE and TAURINE
They intervene in the synthesis of BILE
ACIDS Bile acids are formed in the liver from
cholesterol, conjugated to glycine and taurine,
stored and concentrated in the gallbladder, and
secreted into the intestine after the ingestion
of a meal Bile acids, favouring emulsification
of fats, permit absorption of diet lipids and
liposoluble vitamins (Vit. A, Vit. D, Vit. E,
Vit. K, carotenes)
53
GLYCINE

• Important in the metabolism of creatinine, an
  indispensable substance in contraction of muscle
  fibres
• Participates in synthesis of acetylcholine, which
  transmits nervous stimuli to the muscles

Permits the recovery of muscular function
54
METABOLASE Energising action

• Fructose
• Sorbitol

55
FRUCTOSE
Fructose, or levulose, is the form of sugar found
in fruit and honey
It is a monosaccharide with the same empirical
formula as glucose but with a different structure
Rapid metabolisation in the liver
Readily utilisable energy source
It does not alter glycemia (metabolism not
regulated by insulin)
56
SORBITOL
Sorbitol is a sugar alcohol the body uses slowly

• It has also a diuretic action which favours
  normalisation of renal activity, often
  compromised in states of toxicosis
• It reactivates hepatic function, particularly
  increasing production of bile

57
INDICATIONS

• Ketosis and acidosis
• Prevention and therapy of hepatic steatosis
  (fatty liver)
• Alterations in acidity of milk (hypoacidity,
  hyperacidity) and its transformability (poor
  coagulation)
• Pregnancy toxemia
• Hepatopathy, whether of an infectious or
  parasitic nature or related to pregnancy,
  metabolic dysfunction or diet

58
INDICATIONS

• Toxic states resulting from rumenal toxemia,
  retained placenta, acute mastitis,
  gastroenteritis
• Dietary intoxication, from mycotoxins or of
  iatrogenic origin
• Fatigue, exhaustion, low performance (high-yield
  or competition animals)
• Convalescence, post-operational recovery
• Anorexia and inappetence
• Stress

59
ADMINISTRATION AND DOSAGE

• Administer by the parenteral route
• Cattle, other large adult ruminants, adult
  horses, adult swine 250-500 ml twice daily by
  the intravenous,subcutaneous or intraperitoneal
  routes
• Calves, buffalo calves, foals and adult sheep and
  goats 250 ml twice daily by the
  intravenous,subcutaneous or intraperitoneal routes

60
ADMINISTRATION AND DOSAGE

• Piglets and fattening pigs 20-40 ml/10 kg b.w.
  twice daily by the subcutaneous route
• Lambs and goat kids 20-40 ml/10 kg b.w. twice
  daily by the intravenous, subcutaneous or
  intraperitoneal routes
• Rabbits and cats 2-4 ml/kg b.w. twice daily by
  the subcutaneous route, using various injection
  sites
• Dogs 2-4 ml/kg b.w. twice daily by the
  intravenous or subcutaneous routes

61
METABOLASE
No withdrawal times for meat and milk

• PACKING
• 500-ml bottle