ALCOHOL LIVER DISEASE
•Alcohol related liver disease has been rapidly growing since 1960 as a
result of overconsumption of alcohol that damages the liver further
leading to buildup of fats, inflammation and scarring.
•Alcoholic liver disease presents a broad spectrum of disorders ranging
from simple fatty liver to severe forms of liver injury including alcoholic
hepatitis, cirrhosis and superimposed hepatocellular carcinoma.
•The studies so far had suggested that ethanol metabolism causes
oxidative stress, glutathione depletion , malnutrition , leakage of gut
endotoxins and subsequent activation of kupffer cells that plays a key
role in pathogenesis of alcohol liver disease.
EPIDEMIOLOGY OF ALCOHOL
LIVER DISEASE
Safe limits for alcohol intake
x Males = 21 units per week (1 unit =glass or half pint)
x Females = 14 units per week
Factors increasing susceptibility to ALD
x Lifetime intake of alcohol
x Female sex
x Genetic factors
x Drinking without food
x Binge drinking
x High concentration alcoholic drinks—for
example, spirits
x Drinking multiple different alcoholic
beverages
SPECTRUM OF ALCOHOLIC LIVER
DISEASE
The three most widely recognized forms of ALD are alcoholic fatty liver
(steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis.
Alcoholic fatty liver disease
Histological features of ALD
A large proportion of the cytoplasm of affected
Steatosis (fatty liver) hepatocytes is occupied by a single large
Mallory’s hyaline bodies triglyceride occlusion but liver function is often
normal.
Cholestasis
Acute alcoholic hepatitis
Liver fibrosis
Hepatocytes ballooning occurs due to increased
Micronodular cirrhosis intracellular water Accumulation.
There is prominent Cholestasis.
Alcoholic cirrhosis
Cirrhosis is the most severe form of alcoholic
liver injury and is usually of the Micronodular
type. Collagen deposition can be pericellular, in the
space of Disse, and around central veins (central
hyaline sclerosis).
PATHOGENESIS OF ALCOHOL LIVER
DISEASE
Ethanol and acetaldehyde oxidation by ADH and CYP2E1 generate higher levels of
NADH, which alters the cellular redox potential and enhances lipid synthesis (i.e.,
lipogenesis).
Higher expression of lipogenic enzymes and cytokines that are encoded by genes
regulated by two transcription factors, sterol regulatory element binding protein-1c
(SREBP-1c) and early growth response-1 (Egr-1). SREBP-1c belongs to a family of
transcription factors that control hepatic cholesterol metabolism.
The enhanced generation of NADH by both ADH and ALDH2-catalyzed reactions
decreases the normal intra hepatocytes NAD+/NADH ratio, called the cellular redox
potential. This change causes significant metabolic shifts from oxidative metabolism
toward reductive synthesis, favoring the formation of fatty acids, which contribute to
fatty liver development.
Ethanol metabolism triggered Reactive oxygen species (ROS) production during
both chronic and acute alcoholism7. A variety of cytokines like TNF-α and IL-6 can
be also produced in hepatocytes induced by oxidative stress, which might increase
inflammation.
MECHANISM OF ACTION OF ASTAGLUON
Astaxanthin has tremendous ability to quench free radicals and prevents the process
of lipid peroxidation and stops the ill effects produced due to free radical generation.
Astaxanthin blocks the formation of TNF a and cytokines which play a very
critical role in inflammation and generation of cytokines and chemokines which are
called as messengers of inflammation and fibrosis.
ROS over-production impairs the intracellular GSH homeostasis, leading to GSH
deficiency, Reduced glutathione in the formulation is the eternal source and helps in
the formation of GSH which is the natural source of maintaining redox status of the cell
leading to normal balance of lipogenesis and lipolysis. It also helps in fatty acid
metabolism.
PHARMACEUTICAL INFORMATION
Brand name: Astagluon
Drug name: Astaxanthin and reduced glutathione
Composition: Each capsule contains Astaxanthin and reduced glutathione 4 mg and 250 mg
respectively.
Recommended for:
Radiation induced fibrosis
Patients having hepatocellular toxicity.
Patients of alcohol induced liver diseases.
Dosage: 1 capsule two times a day
Stability and storage condition: STORE in a cool and dry place
