SAFETY AND EFFICACY OF AGE IN DOGS

YAMATO O. et al. 2018

Garlic (Allium sativum) is a bulbous cultivated plant, recently assigned to the Amaryllidaceae family. Always used as a simple seasoning in the kitchen, it is now equally known for its therapeutic properties supported at first by popular beliefs and corroborated now by science.

Countless are in fact the positive effects on human health known since ancient times and which have led it to be currently used with excellent results as a supplement for the control of various pathologies such as cardiovascular diseases, intestinal disorders, atherosclerosis, hypertension and other types of diseases and disorders with scientifically proven efficacy.
It is in fact rich in inulin, amino acids, sulfur, zinc, potassium and phosphorus. It also contains vitamin A and C, calcium, magnesium, manganese, selenium, germanium and B complex vitamin.
The use in dogs and cats has long been considered harmful and linked to the onset of a type of hemolytic anemia specified by oxidative damage to red blood cells with early apoptotic conditions of these cells; this leads to a reduction of the hematocrit, consequently to the level of oxygenation of the blood and all that follows from the systemic point of view. However recent studies have shown that in reality the use in formulations and inclusion levels appropriate and in terms of time of administration and concentration of this plant, do not involve in harmful effects but rather beneficial effects. A study was conducted at the Research Institute of Animal Science in Biochemistry and Toxicology in Japan in which was evaluated efficiency of aged garlic extract (AGE) as a supplement to maintain dog health or as a support for the prevention of multiple diseases.
It has been chosen, in this study, to use aged garlic as it does not contain the characteristic odor which makes it not very palatable and irritating for the gastric mucosa.
The study was conducted on a sample of 9 Beagle dogs of 3 years of age, weighing between 11 and 13 kg, as pathologies and divided into 3 groups of men and women.
Each group was given a different inclusion level of AGE:
– to the first group was administered at 45mg / kg / day
-to the second group was administered at 90mg / kg / day
-to The third party, which constitutes the control group, was managed alone without AGE integration
All dogs were fed with 230 gr of dry food per day and have been evaluated on day 0, 4 weeks, 8 weeks and 12 weeks. The evaluation factors were: appearance of the hair, changes in body weight, changes in appetite, characteristics of the stool and color of the urine. The aim of the study was to research the safe inclusion level of AGE and evaluate the effects of prolonged use on dogs and with the data collected, to design a safe supplement to be used on them.
After 4 and 8 and 12 weeks of administration, no significant changes in blood count and serum parameters occurred in the two groups treated with AGE. Analyzing blood samples, no oxidative damage was observed and no Heinz bodies have been observed, such as cytoplasmic inclusions of the erythrocytes indicating hemoglobin precipitation following damage of various kinds including oxidative damage responsible for hemolytic anemia.
A slightly significant variation was observed in the activity of LDH, the lactate dehydrogenase enzyme but since it is a non-specific enzyme its variation can be linked to alterations in the functionality of any of the organs to which it refers and therefore must always be interpreted in relation to alterations of other blood chemistry values and this leads to consider that small fluctuations may be present even in normal conditions and a single altered value in the absence of symptoms is not considered significant; in this specific case it was not considered attributable to the AGE, as well as the occasional episodes of vomiting and faeces of poor consistency found in 3 dogs with sporadic episodes in the 12 weeks of the study.
A frequent activation of the gene that encodes the Nrf2 factor in the second group of dogs with AGE compared to the control group was also found.
The erythroid-2 nuclear transcription factor (Nrf2) regulates the gene expression of a large variety of genes that code for proteins involved in antioxidant defenses and for enzymes involved in detoxification processes, becoming an important regulator of cellular responses against environmental stress.
The increase in Nrf2 in the second group of dogs was considered significant.
The activity of Nrf2 is regulated at various levels and with different mechanisms; among these, the best studied is the Nrf2 / Keap1 system which is based on the nuclear availability of Nrf2 itself. The integration of AGE also brings sulfur molecules between the various elements that can deactivate the Keap1 gene which is responsible for the coding of a Nrf2, normally sequestered in the cytoplasm because linked to the Keap1 protein here Nrf2 is continuously degraded through a ubiquitination system and is Keap1 has been shown to be directly linked to the degradation processes of Nrf2 and thus represses its activity.
Undegraded Nrf2 moves to the nucleus where it dimers with Maf proteins, small transcription factors, to form a heterodimer that can bind the antioxidant response element located in the regulatory regions of many cytoprotective enzymes on DNA.

Garlic is believed to be responsible for hemolytic anemia due to its sodium thiosulphate content considered to be the cause of the oxidation process of erythrocytes with consequent formation of Heinz bodies; however, estimating the physiological survival time of the canine erythrocytes at 100 days and considering that the experiment lasted for 84 total days, it can be seen that with the passage of 84% of the average life of the red blood cells, no appreciable variations were detected. The study concludes that AGE, not containing, unlike fresh garlic, sodium thiosulphates, is safe administered at inclusion level of 90 mg / kg / day for 12 weeks, in pathology-free Beagles. However, since slight intestinal inflammation was found in a dog, it was concluded that supplements or drugs based on AGE for dogs must contain a mucoprotective substance. Moreover, AGE not only induces response from Nrf2 but upregulates multiple genes related to antioxidation action and detoxification.

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