Biochemical Parameter

Tissue localization

Cellular localization

Histopathological  lesion

Reason of abnormality

References

Alanine aminotransferase (EC 2.6.1.2)

Primarily liver; trace amounts in skeletal muscles and heart

Cytoplasm and mitochondria

Hepatocellular necrosis

Leakage from damaged tissues

[71,72,73]

Aspartate aminotransferase (EC 2.6.1.1)

Liver, heart, muscle, brain and kidney

Cytoplasm and mitochondria

Hepatocellular necrosis

Leakage from damaged tissues

[71,72,75]

Alkaline phosphatase (EC 3.1.3.1)

Liver, bile duct, bone, placenta, kidney and intestine

Cell membrane

Hepatobiliary injury and cholestasis

Overproduction and release in blood

[4,76]

γ-Glutamyl transferase (EC 2.3.2.2)

Kidney, liver, bile duct, pancreas

Cell membrane

Hepatobiliary injury and cholestasis

Overproduction and release in blood

[79,80]

Total bilirubin

Direct (Liver, bile, small intestine, large intestine) Indirect (Reticuloendothelial cells of spleen, serum)

Extracellular fluid

Hepatobiliary injury and cholestasis

Decreased hepatic clearance

[4,75,81]

Urine bilirubin

Urine

 

Hepatobiliary disease

Leakage of conjugated bilirubin out of the hepatocytes into urine

[82]

Urobilinogen

Large intestine, urine

 

Hepatocellular dysfunction

An increase in unconjugated bilirubin, due to increased breakdown of RBCs, which undergoes conjugation, excretion in bile and metabolism to urobilinogen

[82]

Bile acids

Produced in liver, stored in gall bladder and released into the intestine

 

Hepatobiliary disease

Regurgitation into blood along with conjugated bilirubin

[83,84]

Prothrombin time

 

 

Hepatocellular dysfunction

Decreased synthetic capacity

[82]

Lactate dehydrogenase (EC 1.1.1.27)

Liver peroxisomes, muscles, kidney, heart

Mitochondria and sarcoplasmic reticulum

Hepatocellular necrosis

Leakage from damaged tissue

[82]

Sorbitol dehydrogenase (EC 1.1.1.14)

Liver, kidney, seminal vesicle, intestine

Cytoplasm, mitochondria

Hepatocellular necrosis

Leakage from damaged tissue

[75]

Glutamate dehydrogenase (EC 1.4.1.2)

Liver, kidney

Mitochondrial matrix

Hepatocellular necrosis

Leakage from damaged tissues

[75,85]

Albumin

Produced in liver

Blood plasma

Hepatic dysfunction

Decreased synthesis

[82]

Total protein

Produced in liver and immune system

Blood plasma

Hepatic dysfunction

Decreased synthetic capacity

[82]

Serum F protein

Liver, kidney

Primarily cytoplasm

Hepatocellular necrosis

Leakage from damaged tissue

[87,88]

Glutathione-S-transferase (EC  2.5.1.18)

Liver, kidney

Cytoplasm, mitochondrial, centrolobular cells

Early hepatocyte injury; Hepatocellular necrosis

Readily released from hepatocytes in response to injury

75,91

Arginase I (EC 3.5.3.1)

Liver

Cytoplasm

Hepatocellular necrosis

Release from injured hepatocytes

[75,93,94]

Malate dehydrogenase (EC 1.1.1.37)

Liver, heart, muscle, brain

Cytoplasm, mitochondria

Hepatocellular necrosis

Leakage from damaged tissues

[75,97,99]

Purine nucleoside phosphorylase (EC 2.4.2.1)

Liver, muscle, heart

Cytoplasm of endothelial cells, kupferr cells, hepatocytes

Hepatocellular necrosis

Released into hepatic sinusoids with necrosis

[75]

Paraoxonase 1 (EC 3.1.8.1)

Liver, kidney, brain, lung

Cytoplasm, microsomal, endoplasmic reticulum

Hepatocellular necrosis

Not a leakage enzyme; reduced hepatic synthesis and secretion

[75,102]

Table 1: Biochemical markers of hepatotoxicity in blood plasma and serum.