192
Dyslipidemia may be another furan toxicity risk. Liver is an important source of
lipid metabolism and plays a crucial part in serum protein synthesis. Chronic liver
disorders decrease the biosynthetic efficacy and ability of the liver and subsequently
decrease the triglyceride, cholesterol and HDL-C levels [65]. To identify the hepatic
functions and liver diseases these indicators such as total protein, triglyceride, albumin, cholesterol and glucose can be used as detection marker from medical point of
view. Therefore, it can also indicate catastrophic effect on lipids, protein and glucose synthesis in liver due to furan toxicity [58].
Changes in serum proteins, glucose, cholesterol and triglyceride most likely
determine general metabolic changes in contrast to toxic effect on specific organs
[56]. It should be remembered that there is no specific understanding of the precise
mechanisms involved in these changes. However, inhibition of enzymes involved in
TCA cycle, after exposure to furan, has been indicated via metabolomics analysis
[64]. On the other hand, to compensate for the lack of carbohydrate products, the
use of fatty acids as an energy source is increased. This phenomenon may lead to a
significant reduction in serum TG concentrations. In fact, there may be a significant
increase in different amounts of amino acids due to proteolysis from liver damage
or use of proteins as a source of energy [64]. The mechanism of these changes is
explained in further studies. Another section of the digestive system that may be
affected by furan is exocrine pancreas. Serum amylase is a major gastroenteric
enzyme and is a key indicator of the function of the pancreas [66]. Gavage-based
administration of furan to Fischer-344 rats and mice caused serum amylase increase
at different concentrations [11]. Some studies, however, suggest that in animals with
liver and infectious diseases, amylase could be reduced [67]. Various animal studies
exhibit the effects of furan on the digestive system (Table 12.4). Many mechanisms
are proposed at the cellular level to explain the reasons for the destructive effects of
the furan and its active metabolite, BDA, particularly in hepatic cells called
cytolethality.
Toxicity of Food Contaminant Furan on Liver and Kidney
of Growing Male Rats
Furan is reported in mice and rats as carcinogenic and can also be carcinogenic in
humans [72]. Due to high prevalence of hepatocarcinogenic lesions and carcinomas
recorded in mice it is also considered to be possible hepatocarcinogenic in humans
[69]. CYP2E1 metabolizes furan and transforms it into a cytotoxic metabolite
named, cis-2-butene-1,4-dialdehyde. It then attaches on proteins and nucleotides
irreversibly [6]. The furans toxicity is reported to be linked to cis-2-butene-1,4dialdehyde metabolite [73]. Furan metabolites also cause toxic effects by influencing cell proliferation and dissociation of mitochondrial oxidative phosphorylation
[74]. Furan’s acute impact has not been studied sufficiently, but still chronic low
level is considered to be cancer-related [75]. In the National Toxicology Program
S. Muzammil et al.
Dyslipidemia may be another furan toxicity risk. Liver is an important source of
lipid metabolism and plays a crucial part in serum protein synthesis. Chronic liver
disorders decrease the biosynthetic efficacy and ability of the liver and subsequently
decrease the triglyceride, cholesterol and HDL-C levels [65]. To identify the hepatic
functions and liver diseases these indicators such as total protein, triglyceride, albumin, cholesterol and glucose can be used as detection marker from medical point of
view. Therefore, it can also indicate catastrophic effect on lipids, protein and glucose synthesis in liver due to furan toxicity [58].
Changes in serum proteins, glucose, cholesterol and triglyceride most likely
determine general metabolic changes in contrast to toxic effect on specific organs
[56]. It should be remembered that there is no specific understanding of the precise
mechanisms involved in these changes. However, inhibition of enzymes involved in
TCA cycle, after exposure to furan, has been indicated via metabolomics analysis
[64]. On the other hand, to compensate for the lack of carbohydrate products, the
use of fatty acids as an energy source is increased. This phenomenon may lead to a
significant reduction in serum TG concentrations. In fact, there may be a significant
increase in different amounts of amino acids due to proteolysis from liver damage
or use of proteins as a source of energy [64]. The mechanism of these changes is
explained in further studies. Another section of the digestive system that may be
affected by furan is exocrine pancreas. Serum amylase is a major gastroenteric
enzyme and is a key indicator of the function of the pancreas [66]. Gavage-based
administration of furan to Fischer-344 rats and mice caused serum amylase increase
at different concentrations [11]. Some studies, however, suggest that in animals with
liver and infectious diseases, amylase could be reduced [67]. Various animal studies
exhibit the effects of furan on the digestive system (Table 12.4). Many mechanisms
are proposed at the cellular level to explain the reasons for the destructive effects of
the furan and its active metabolite, BDA, particularly in hepatic cells called
cytolethality.
Toxicity of Food Contaminant Furan on Liver and Kidney
of Growing Male Rats
Furan is reported in mice and rats as carcinogenic and can also be carcinogenic in
humans [72]. Due to high prevalence of hepatocarcinogenic lesions and carcinomas
recorded in mice it is also considered to be possible hepatocarcinogenic in humans
[69]. CYP2E1 metabolizes furan and transforms it into a cytotoxic metabolite
named, cis-2-butene-1,4-dialdehyde. It then attaches on proteins and nucleotides
irreversibly [6]. The furans toxicity is reported to be linked to cis-2-butene-1,4dialdehyde metabolite [73]. Furan metabolites also cause toxic effects by influencing cell proliferation and dissociation of mitochondrial oxidative phosphorylation
[74]. Furan’s acute impact has not been studied sufficiently, but still chronic low
level is considered to be cancer-related [75]. In the National Toxicology Program
S. Muzammil et al.