191
necrosis [11, 53]. For this differential liver lobes susceptibility to furan, three likely
explanations have been suggested [11]. One explanation is caudate liver lobe allows
portal venous circulation; therefore, it show higher exposure as compared to left,
right and median lobes [11]. Another explanation is, there are intrahepatic lobe variations, in furan metabolism [54] and lastly, as left or caudated liver lobes are next to
the stomach, therefore raising the risk of direct furan spreading through the stomach [11].
Biochemical parameter of serum is usually evaluated for toxicology and liver
damage assessment prior to histopathology confirmation [55]. Many enzymes present in liver such as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) are conjugated to bilirubin. Bilirubin is
released into the circulation after the cell damage [56], which make them most
sensitive biomarkers for any liver injury [11]. Among them, ALT is consider to be
most specific enzyme for hepatocyte damage evaluation [13]. Moser et al. illustrated in an animal study that mice treated with 1, 2, 4, and 8 mg/kg body weight
furan increased dose-dependent levels of ALT, with evidence of hepatotoxicity at
even lower concentrations. Enhanced hepatocarcinogenesis in doses above 4.0 mg/
kg body weight was also noticed [13]. In another test, in mice with both sexes at
8 mg / kg furan body weight, Gill et al. showed a significant improvement in ALT
function. The behaviours of ALP and AST in male and female rats were both consistent in this experiment [11]. After administration of furan through nasogastric
gavage for 90 days at different doses to rats previously treated with furan, improvements in enzyme activity, elevated conjugated and total bilirubin levels are observed
[11]. Increases in overall bilirubin that result from cholestasis following intrahepatic or extrahepatic bile flow deficiency induced by the release of enzymes attached
to the hepatic membrane [11, 53].
Furan and its derivatives effect on digestive system including effect on liver,
proposed that after exposure of furan these tissues undergo to high risk [57]. Some
opposing results can also be observed due to many factors as exposure times, animal
age and furan dose [58]. Gamma glutamyltranspeptidase (GGT or γ-GT), a plasma
membrane enzyme, [59] level increases in many diseases such as liver and cardiovascular disorders and diabetes mellitus [60]. Therefore, rendering it a reliable
marker for diseases detection. Some drugs and alcohol are also responsible for
higher level of GGT in cell and tissues. Furthermore, there is evidence that cell
resistance during oxidative stress is increased due to increase in GGT expression,
which is responsible for GSH synthesis that boosts the cell resistance. Increased
GGT level plays crucial role in oxidative stress regulation [61]. A correlation has
been studied between hepatic steatosis and plasma GGT [62]. In older people higher
serum GGT level is suggested to be associated with liver and cardiovascular diseases [62]. Its higher level, out of normal range also serves as biomarker for atherosclerosis [63]. A direct and strong correlation between GGT level and urinary furan
has been determined in a cross-sectional study. Though animals and in vitro experiments are subject to higher furan dose as compared to what human are exposed to
naturally. But this experiment results concluded that the amount of furan received
by human can also be destructive to tissues and oxidative reaction [64].
12 Role of Furans as EDCs in Metabolic Disorders
necrosis [11, 53]. For this differential liver lobes susceptibility to furan, three likely
explanations have been suggested [11]. One explanation is caudate liver lobe allows
portal venous circulation; therefore, it show higher exposure as compared to left,
right and median lobes [11]. Another explanation is, there are intrahepatic lobe variations, in furan metabolism [54] and lastly, as left or caudated liver lobes are next to
the stomach, therefore raising the risk of direct furan spreading through the stomach [11].
Biochemical parameter of serum is usually evaluated for toxicology and liver
damage assessment prior to histopathology confirmation [55]. Many enzymes present in liver such as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) are conjugated to bilirubin. Bilirubin is
released into the circulation after the cell damage [56], which make them most
sensitive biomarkers for any liver injury [11]. Among them, ALT is consider to be
most specific enzyme for hepatocyte damage evaluation [13]. Moser et al. illustrated in an animal study that mice treated with 1, 2, 4, and 8 mg/kg body weight
furan increased dose-dependent levels of ALT, with evidence of hepatotoxicity at
even lower concentrations. Enhanced hepatocarcinogenesis in doses above 4.0 mg/
kg body weight was also noticed [13]. In another test, in mice with both sexes at
8 mg / kg furan body weight, Gill et al. showed a significant improvement in ALT
function. The behaviours of ALP and AST in male and female rats were both consistent in this experiment [11]. After administration of furan through nasogastric
gavage for 90 days at different doses to rats previously treated with furan, improvements in enzyme activity, elevated conjugated and total bilirubin levels are observed
[11]. Increases in overall bilirubin that result from cholestasis following intrahepatic or extrahepatic bile flow deficiency induced by the release of enzymes attached
to the hepatic membrane [11, 53].
Furan and its derivatives effect on digestive system including effect on liver,
proposed that after exposure of furan these tissues undergo to high risk [57]. Some
opposing results can also be observed due to many factors as exposure times, animal
age and furan dose [58]. Gamma glutamyltranspeptidase (GGT or γ-GT), a plasma
membrane enzyme, [59] level increases in many diseases such as liver and cardiovascular disorders and diabetes mellitus [60]. Therefore, rendering it a reliable
marker for diseases detection. Some drugs and alcohol are also responsible for
higher level of GGT in cell and tissues. Furthermore, there is evidence that cell
resistance during oxidative stress is increased due to increase in GGT expression,
which is responsible for GSH synthesis that boosts the cell resistance. Increased
GGT level plays crucial role in oxidative stress regulation [61]. A correlation has
been studied between hepatic steatosis and plasma GGT [62]. In older people higher
serum GGT level is suggested to be associated with liver and cardiovascular diseases [62]. Its higher level, out of normal range also serves as biomarker for atherosclerosis [63]. A direct and strong correlation between GGT level and urinary furan
has been determined in a cross-sectional study. Though animals and in vitro experiments are subject to higher furan dose as compared to what human are exposed to
naturally. But this experiment results concluded that the amount of furan received
by human can also be destructive to tissues and oxidative reaction [64].
12 Role of Furans as EDCs in Metabolic Disorders