190
glutathione (GSH) in aqueous incubate [49]. Partial reduction of GSH is caused by
2-methylfuran in haemolysates. For this depletion of GSH, 2- methylfuran must be
co-incubated with microsomal bioactivating system. This indicates that bioactivation of 2-methylfuran is required, which is available in erythrocyte cytosol or in
microsomal system. It can be inferred from previous knowledge of biotransformation that alkylfurans can also be oxidized at the sidechain to allow furyl alcohols to
grow and oxidize to create the required acids and aldehydes. These additional
metabolism routes and their effects on substances toxicity have not been studied.
Furan Biotransformation Enzymes
The main contributor to the metabolism of furans is CYP2E1 [50]. A study indicates
correlation between p-nitrophenol (CYP2E1 substrate) conversion and furan metabolism in human microsomal incubations. Among all CYPs the highest activity was
observed in CYP2E1, at least 5–10 times greater than other forms. For numerous
other CYPs types minimal catalytic activity was observed [51]. Alizadeh et al. [50]
demonstrated that CYP-catalysed biotransformation of furan results in inactivation
of CYPs and that CYP2E1 is more heavily affected than other CYPs. From metabolism studies with 2-methylfuran with inducers and inhibitors of CYP2E1 [48], it
may be anticipated that also this alkylated furan and possibly also 3-methylfuran are
metabolized predominantly by CYP2E1, but contrary to furan, studies with purified
CYP enzymes are not available for these two alkyl furans. Therefore, there is no
direct evidence for an involvement of CYP2E1 in the biotransformation of 2- and
3-methylfuran. Reports of CYP2E1 metabolism with 2-methylphuran inducers and
inhibitors [48] may also predict that CYP2E1 is also the primary metabolism of this
furan alkylated, probably even3-methylfuran, however, unlike furan, reports of
these two alkyl furans are not possible with pure CYP enzymes. There is therefore
no direct evidence for the CYP2E1’s role in 2-and3-methylfuran
biotransformation.
Risks of Furan to Digestive Track and Enzymes
Furan mainly target liver and cause toxic and carcinogenic effects [12]. Due to high
ability of cytP2E1 furan is bioactivated into a reactive intermediate
BDA. Hepatocellular changes and disruption to the epithelium of bile duct which
can result in cholangio fibrosis and the further production of cholangio carcinomas
could be attributed to the hepatotoxicity impact of furan [52]. Major elimination
route for furan removal is bialiary excretion [45]. As a consequence, prolonged
exposure to furan metabolites toxicity in the bile duct results in damage to the epithelium layer of bile duct [7]. The caudate lobes and left subcapsular surface of liver
are highly exposed to furan toxic effects including fibrosis, inflammation and
S. Muzammil et al.
glutathione (GSH) in aqueous incubate [49]. Partial reduction of GSH is caused by
2-methylfuran in haemolysates. For this depletion of GSH, 2- methylfuran must be
co-incubated with microsomal bioactivating system. This indicates that bioactivation of 2-methylfuran is required, which is available in erythrocyte cytosol or in
microsomal system. It can be inferred from previous knowledge of biotransformation that alkylfurans can also be oxidized at the sidechain to allow furyl alcohols to
grow and oxidize to create the required acids and aldehydes. These additional
metabolism routes and their effects on substances toxicity have not been studied.
Furan Biotransformation Enzymes
The main contributor to the metabolism of furans is CYP2E1 [50]. A study indicates
correlation between p-nitrophenol (CYP2E1 substrate) conversion and furan metabolism in human microsomal incubations. Among all CYPs the highest activity was
observed in CYP2E1, at least 5–10 times greater than other forms. For numerous
other CYPs types minimal catalytic activity was observed [51]. Alizadeh et al. [50]
demonstrated that CYP-catalysed biotransformation of furan results in inactivation
of CYPs and that CYP2E1 is more heavily affected than other CYPs. From metabolism studies with 2-methylfuran with inducers and inhibitors of CYP2E1 [48], it
may be anticipated that also this alkylated furan and possibly also 3-methylfuran are
metabolized predominantly by CYP2E1, but contrary to furan, studies with purified
CYP enzymes are not available for these two alkyl furans. Therefore, there is no
direct evidence for an involvement of CYP2E1 in the biotransformation of 2- and
3-methylfuran. Reports of CYP2E1 metabolism with 2-methylphuran inducers and
inhibitors [48] may also predict that CYP2E1 is also the primary metabolism of this
furan alkylated, probably even3-methylfuran, however, unlike furan, reports of
these two alkyl furans are not possible with pure CYP enzymes. There is therefore
no direct evidence for the CYP2E1’s role in 2-and3-methylfuran
biotransformation.
Risks of Furan to Digestive Track and Enzymes
Furan mainly target liver and cause toxic and carcinogenic effects [12]. Due to high
ability of cytP2E1 furan is bioactivated into a reactive intermediate
BDA. Hepatocellular changes and disruption to the epithelium of bile duct which
can result in cholangio fibrosis and the further production of cholangio carcinomas
could be attributed to the hepatotoxicity impact of furan [52]. Major elimination
route for furan removal is bialiary excretion [45]. As a consequence, prolonged
exposure to furan metabolites toxicity in the bile duct results in damage to the epithelium layer of bile duct [7]. The caudate lobes and left subcapsular surface of liver
are highly exposed to furan toxic effects including fibrosis, inflammation and
S. Muzammil et al.