Hepatoprotectors: Definition, Function, Hepatotoxicity, Hepatotropic Agents and Disorders Associated with Metabolism

The liver is one of the largest organs in the human body and the primary site for intense metabolism and excretion.


It has a fantastic role in maintaining, performing, and regulating the body’s homeostasis.

It is involved with almost all biochemical pathways for growth, disease-fighting, nutrient supply, energy supply, and reproduction.

Liver damage is always associated with cell necrosis, increased tissue lipid peroxidation, and depletion of tissue glutathione levels.

In addition, serum levels of many biochemical markers, such as glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase, triglycerides, cholesterol, bilirubin, and alkaline phosphatase are elevated.

The following are some of the commonly seen liver diseases:

  • Necrosis.
  • Cirrhosis.
  • Hepatitis can be viral and toxic.
  • Acute or chronic liver failure.
  • Liver disorders due to impaired metabolic function.

Disorders associated with metabolism

Disorders associated with fat metabolism are fatty liver, disorders related to bilirubin metabolism, drug- and chemical-induced hepatotoxicity, and jaundice, which can be of different types depending on the mechanisms of action and etiology:


  • Hemolytic and prehepatic jaundice.
  • Obstructive jaundice (post-hepatic and cholestatic jaundice).
  • Hepathogenic and hepatic jaundice and cholestasis.
  • Hereditary jaundice or pure cholestasis such as Gilbert syndrome, Dubin Johnson syndrome, and Crigler-Najjar syndrome, among others. Rotor syndrome is one of the types of inherited jaundice.

The liver

The liver is a vital organ of the digestive system; it is also the largest organ in the body.

Most of its cells are hepatocytes, but Kupfer cells, stellate cells, and others.

Hepatocytes play many vital roles in maintaining homeostasis and health.


Hepatotoxin is a non-toxic chemical that damages the liver.

Toxic liver injury from drugs and chemicals can mimic virtually any form of natural liver disease.

The hepatoprotective effect against chemicals and the hepatotoxicity induced by alcohol, carbon tetrachloride, galactosamine, paracetamol, isoniazid and rifampicin, antibiotics, peroxidized oil, and aflatoxin, among others, were studied.

The severity of hepatotoxicity is significantly increased if the drug is continued after symptoms develop.

Among the various inorganic compounds that cause hepatotoxicity are arsenic, phosphorus, copper, and iron.

Organic agents include certain naturally occurring plant toxins, such as pyrrolizidine alkaloids, mycotoxins, and bacterial toxins.

Liver injury caused by hepatotoxins, such as carbon tetrachloride, ethanol, and acetaminophen, is characterized by varying degrees of hepatocyte degeneration and cell death from apoptosis or necrosis.

Hepatotoxin metabolism by cytochrome P-450 enzyme subtypes is crucial in intoxication; therefore, enzyme inhibitors are shown to minimize liver damage associated with hepatotoxins.

Furthermore, there is substantial evidence that the mitochondrial permeability transition involves hepatocellular injury.

It is associated with reactive oxygen species, and the new findings offer a new therapeutic approach to attenuate cell damage by blocking the onset of the mitochondrial permeability transition.

Therefore, oxidative stress and lipid peroxidation are crucial elements that lead to hepatotoxin-associated liver injury.

In addition to specific treatment for a given hepatotoxin, the general strategy for the prevention and treatment of damage includes reducing the production of reactive metabolites of the hepatotoxins.

Antioxidant agents treat and selectively target Kupffer cells or hepatocytes for ongoing processes.


Treatment of liver diseases can be done in different ways, depending on the etiology and pathogenesis of the disease that has been treated.

These therapies include:

  • Changes in diet
  • Change in health lifestyle.
  • Surgical treatment.
  • Use of hepatoprotective drugs.


Hepatoprotectors are drugs responsible for the protection of hepatocytes against toxic agents, which act in at least one of the following mechanisms:

  • Stabilization of the hepatocyte membrane.
  • Neutralization of free radicals.
  • Increase in the synthesis or inhibition of glutathione oxidation.
  • Blocking the penetration of toxic substances into hepatocytes.
  • Decrease in liver inflammation.
  • Increased synthetic activity of RNA polymerase.

hepatotropic agents

In this group of drugs, there are hepatotropic agents and lipotropic agents (which prevent the deposition of lipids in the liver).


Silymarin contains one of the most potent antioxidants known; this action prevents the formation of free radicals and notably prevents toxins that cause acute or chronic diseases in the tissue and liver function.

Silymarin is also an effective stimulant of protein synthesis, which allows the liver to perform its functions at total capacity.

Silymarin is recommended to treat chronic inflammatory disorders of the liver and the remarkable results in preventing intoxications due to alcoholism, chronic hepatitis, and cirrhosis conditions.


Lipotropic elements such as Lecithins, Inositol, and Choline, adhere to fat molecules and transform them into more accessible transportable forms, speeding up their removal from the liver.

Lipotropics work by preventing fatty liver and inflammatory conditions.

When the bile enters the intestine, the soluble cholic acid, excreted by the bitterness, is absorbed into the bloodstream and carried by the blood back to the liver and again excreted with the bile to the intestine and reabsorbed until completing cycle after cycle.

Magnesium oxide and calcium carbonate create by combining with cholic acid and achieve an insoluble form, which cannot be absorbed in the intestine and is excreted with the feces.

This physiological form causes a drastic reduction in the amounts of fat in the liver and cholesterol levels in the blood without causing any side effects.

Choline is a water-soluble lipotropic agent. It is generally grouped within the B complex vitamins.

Choline is believed to promote the conversion of liver fat into choline-containing phospholipids, which can be rapidly transferred from the liver to the bloodstream, bypassing liver steatosis.

Choline deficiency can play a role in liver disease, atherosclerosis, and possibly neurological disorders.

One symptom of choline deficiency is an elevated level of the liver enzyme ALT.

The most often available choline supplement is lecithin, derived from soy or egg yolks.


Loss of liver storage capacity almost always leads to a decrease in B-Complex vitamins.

These vitamins have a protective action on the liver, compensate for the amounts of vitamins required by the liver, and stimulate the detoxifying function.

The elimination of fats by Lipotropics and the alkalizing power of Magnesium and Calcium adds a refreshing digestive and antacid action to silymarin capsules, lipotropics, and vitamins of the B complex, especially if it is ingested after each meal.