Liver- The Unsung Soldier

All living animal body is filled with four basic substances called as HUMORS, which are in balance when the animal is healthy. All disabilities and diseases are the final presentation of excess or deficit of any one of these humors viz., Black bile, yellow bile, phlegm and blood. Dyscrasia, imbalance of humors is considered as the direct cause of all disease. Eucrasia or Humors in balance is associated with good health. The nature of diseases is highly influenced by the qualities of humors. Warm diseases are caused by yellow bile and cold diseases are caused by phlegm. 

Being with the characteristics of FIRE, the organ LIVER is considered to be one of the superior organs from ancient times. As named, it is considered as the seat of metabolism of all products and performs more than 500 functions for the body to lead a normal life in a living being. An impaired liver can impact on these 500 + functions.

Like this saying, “I am a sick man… I am a spiteful man, I am an unpleasant man. I think my liver is diseased.” ?Fyodor Dostoevsky

The liver is considered as the master organ for producing optimal nutrition for all the 50 trillion cells in the animal body. It is praised as the "alchemical wizard" of the body, transforming toxins into harmless chemicals for excretion and digestively absorbed nutrients into the proper biochemical forms to nurture the cells to function normally. Yet the liver is probably the organ most stressed by toxic materials. Liver is a key organ that is involved in 

There is a direct relation between the nutritional status and milk synthesis especially during the postpartum conditions (Waters. S et al., 2006). Increasing milk production increases the energy demand, thereby induces the liver to produce glucose from non-carbohydrate sources by Gluconeogenesis. The factors prevent animals from feed intake and the likelihood of development of Ketosis increases drastically where the metabolic signals like glucocorticoids, catecholamine enhance the breakdown of lipids and delivers Non-Esterified Fatty Acids to liver. The resident macrophages in adipose tissues could attract Cytokines and other proinflammatory mediators into the liver which will in turn reacted by the hepatic cells and kupffer cells in the form of inflammation of liver. Ultimately an inflamed liver/ Ketoic liver reduces energy production and metabolism which will also reduce the milk production. Nutrition induced Ketosis during the early post-partum could affect the health of animal and in long term this can have negative effects on reproduction and productive life of animals (Loor J et al, 2007)

Animals are highly prone for parasites due to their increased chance of contact with the parasitic stages. As a whole, parasites cause damage to the animal, both on productivity and health aspects by depleting the energy sources making the organs to starve for the nutrients. Though the effect is for all the organs, liver is highly affected/pushed into stress since it is the master organ which should compensate the energy loss by supplying energy to the 50 trillion cells of the body starving due to the parasites. Apart from production stress due to the parasites, liver also encounters significant damage due to the worms like Liver flukes (Fasciola spp.) which will cause direct trauma to the liver tissue as such. These worms take the nutrients directly from the liver and also damages the hepatocytes which can lead to fibrosis of liver tissues which leads to the impaired functioning of liver. The incidence of parasites will increase significantly in the presence of rains (Sardar. S. A et al, 2006) which is the productive season in India.

Due to the recent scientific developments, presence of chemicals as residue in all food, feed and water is a common scenario. Chemical in μg to kg has to be metabolised by liver cells to safeguard the animal from its toxic effects. Liver cells are the major cells that will face themaximum damage due to the chemicals which ultimately effects on the normal functioning of liver resulting in a cascade of events that ends up in the decreased productivity of the animal.

Good turns bad sometimes where damage to liver is a good example in this regard during treatment. All drugs given internally will be metabolized by liver to exert its' action. During the process, the liver undergoes severe changes depending upon the drugs used, dose and the dosage given. Indiscriminate usage of drugs will be having huge impact on the liver cells. Some drugs will be hepatotoxic in nature (e.g. Albendazole, etc.) (Dayan.A.D, 2003) where administering the drugs in even normal dose can cause damage to the liver.

Increased occurrence of liver diseases can greatly influence on the performance of liver cells. Viral hepatitis, bacterial hepatitis and autoimmune hepatitis causes direct impact on the functions of liver cells where the mechanism varies with the underlying cause for the condition. In viral hepatitis, the presence of virus elicits the immune response on the liver cells and in autoimmune hepatitis, the immune system attacks the liver cells and damages the liver cells due to the autoimmune disease

Damage to liver due to fungus (Aspergillus spp.) is a high risk concern since the chances animals can pick aflatoxin from feed is higher in poorly maintained animals. Aflatoxins are concerned to be the most carcinogenic substance known (Hudler. G, 1998). Liver converts these highly toxic aflatoxins to less toxic Aflatoxin M. High level aflatoxins produce acute hepatic necrosis which may progress to cirrhosis or to carcinoma of the liver.

Many protozoal parasites (like Anaplasmosis) cause a great damage to the liver. Parasitic damage to RBC increases the level of Bilirubin and also anaemic body decreases the effective functioning of Liver. 

 

Manifestation of liver damage will be usually hidden due to compensatory mechanism of liver cells which are pronounced when compared to other cells. Anorexia, fatigue, discomfort and pruritus are commonly noticed. One major notable sign in a liver disease is yellow discolouration of mucous membrane which will increase in intensity based on the severity. The colour of stools also gets more yellowish as the liver damage increases. 

Treating damaged liver involves careful examination followed by clear understanding about the causative agent along with supplementary support to rejuvenate the liver cells. For the treatment of liver insufficiency due to negative energy balance & toxicity, injection of glucose as dextrose along with vitamin B complex or Sodium propionate by mouth may be of good value and if liver fattening is observed, it is advisable to use glucose parenterally. As a supportive to treat liver damage currently, two options are commonly practiced. One is use of liver extracts orally/parenterally and the other is using herbs or their phytochemicals. 

Usage of liver extracts is a commonly used method to treat liver damage of varied aetiologies. Though usage of liver extract (orally or parenterally) is invariably practised by field veterinarians due to its impact on blood production and weight gain, the actual scientific background of its usage for liver damage is a highly debatable topic. The practice of using liver extracts for treating liver ailments started from 1920 by George Wipple for treating spernicious anaemia in humans. The exact reason and the impact of usage were made clear by Karl & Folkers in 1948. They explained that the chemical responsible for the medicinal effect of liver extract is Vitamin B₁₂. But, in ruminants, Vitamin B₁₂ is readily available, as the same is produced by rumen bacteria in significant quantity meeting almost the daily body requirement. In addition, other B-complex vitamins are also produced by microbes; therefore the practice of liver extracts for treating liver disorders is just a symptomatic treatment rather than treating the very root cause. As the liver extracts will only compensate to supplement few vitamins and minerals without treating the underlying problem. More so to it, liver extracts also carry the risk of transferring various infections, if it is improperly sterilized. 

The preliminary goal to deal with liver problem is by enhancing its detoxification potential and to help it to protect itself from getting further damaged (Treadway S, 1998). For this a combination of herbs with specific properties were used which will work on multiple biochemical pathways since ancient times. They are capable of influencing several organ systems & simultaneously their primary site of action will be on the liver. Phytochemicals like Silybin which is available in Silymarin spp. protect the liver by promoting the growth of new liver cells and also inhibits lipid peroxidation. Wedenolactone is a key phytochemical which is having a potent hepatoprotective activity by inhibiting protease activity as well as the activity of phospholipase A2 and it is found that it is a potent and selective inhibitor of 5-Lox activity by Oxygen radical scavenging mechanism thereby exerting its hepatoprotective and anti-inflammatory properties. Wedenolactone is highly available in Eclipta alba. Phyllanthin in plants like Phyllanthus spp. is found to be a potent inhibitor of pro-inflammatory cells Liver Extract injection used during 1929produced during general inflammatory conditions as well as inflammations induced by viral infections. It is having notable antiviral effects also. Herbs like Boerhaavia spp. has vitamins like Vitamin C and E that are essential and also possesses hepatoprotective action against drug induced liver toxicity by augmenting the antioxidative defences. Tumour causing agents like pesticides & aflatoxins can also be counteracted by chemicals like Andrographolidae which is a phytochemical found in Andrographis spp., which attenuates the Tumour Necrosis Factor (TNF-α) and augmenting the elevation of heme oxygenase-1. It also inhibits the inflammation and oxidative stress. Many more herbs like, Terminalia chebula having Chebulin, Picrorhiza kurroa containing Kutkin in it, Embelia ribes containing Embelin, Piper longum which contains Piperlongumin, etc. are used for treating liver dysfunctions. 

HepaAssist® bioreactor acting as artificial liver for humans is among one of the most notable advancements in the liver care for humans. High risk organs like liver require extra care, time to time interventions with proper precautions and timely treatment. Extra care also involves supporting liver during any antibiotic, anthelmintic, chemical therapy etc. which invariably will challenge liver due to their inherent toxicity. Among numerous available options for treating liver disorders in animals, it is wiser to select the best approach which not only attempts to have symptomatic effect but also has long-lasting impact. Phytochemicals have time and often proven to be the best possible support to liver disorders.