Re: Mycotoxins are toxic fungal metabolites

[Guest guest]

Another excellent resource. Contains a lot of valuable information. Thanks,

KC.

tigerpaw2c <tigerpaw2c@...> wrote: V. Sava et al. 3

INTRODUCTION

http://stinet.dtic.mil/cgi-bin/GetTRDoc?

AD=A452374 & Location=U2 & doc=GetTRDoc.pdf

Mycotoxins are toxic fungal metabolites which are structurally

diverse, common

contaminants of the ingredients of animal feed and human food. These

fungal products

exhibit a range of pharmacological activities that have been

utilized in development of

mycotoxins or mycotoxin derivatives as antibiotics, growth

promoters, and other kinds of

drugs; still others have been developed as biological and chemical

warfare agents [1]. Bombs

and ballistic missiles laden with biological agents including

aflatoxin were believed to be

deployed by Iraq during Operation Desert Storm[2]. In light of the

excess incidence of

amyotrophic lateral sclerosis in young Gulf War veterans [3], it is

important not to forget the

potential neurotoxic effects of low doses of mycotoxins. Although

much is known about the

lethal effects of the aflatoxins, little is known about the acute

and long-term effects of less

potent mycotoxins, such as Rubratoxin B (RB), on adult nervous

system.

Rubratoxin B (RB) is a metabolite of the molds Penicillum rubrum and

Penicillum

purpurogenum. These molds commonly contaminate cereals, foodstuffs

and grow on damp

tents and fabrics. RB is not known to produce a serious health

hazard in this naturally

occurring form, but pure RB is a bisanhydride lactone with

hepatotoxic [4] and teratogenic

properties [5, 6, 7]. Investigation of the effects of acute and

chronic exposure to RB on the

nervous system has been scarce, even though neuronal tissue appears

to be very susceptible to

the deleterious effect of RB in teratogenic studies [8].

RB has numerous biochemical actions including the inhibition of (Na+-

K+)-ATPase

[9], inhibition of the hepatic cytochrome P-450-dependent

monooxygenase system[10],

reduction of hepatic and renal nonprotein sulfhydryl content [11]

and inhibition of gap

junctional intercellular communication [12]. It was found that RB

caused shifts in the

V. Sava et al. 4

ultraviolet absorption spectra of DNA and RNA [13]. The observed

binding properties of RB

can disrupt the integrity of DNA and RNA. RB has been shown to

induce apoptosis [14, 15]

and internucleosomal fragmentation of DNA [14].

Studies with isolated mouse liver mitochondria revealed that RB

disrupted

mitochondrial respiration and depressed oxygen consumption[8]. The

principal site of action

of RB in the mitochondrial electron transport system was found to be

between cytochrome C1

and the termination of electron flow [8]. Ochratoxin, a related

mycotoxin, has been

reported to alter mitochondrial respiration and oxidative

phosphorylation through impairment

of the mitochondrial membrane and inhibition of the succinate-

dependent electron transfer

activities of the respiratory chain [16].

The overall objective was to study RB neurotoxicity in the context

of oxidative stress

induced by inhibition of mitochondrial electron transport in brain

tissues. Inhibition of

oxidative phosphorylation would be expected to result in increased

generation of oxyradicals

and decreased production of ATP[17]. We hypothesized that RB-

induced alteration of

oxidative processes would not be homogeneous across all brain

regions but would reflect the

capacity of distinct brain regions to upregulate anti-oxidative

mechanisms and repair

processes. Parameters of oxidative stress measured included lipid

peroxidation

(thiobarbituric acid-reactive substances or TBARS), SOD activity,

oxidative DNA damage

and repair in each of six brain regions cerebellum (CB), cortex

(CX), hippocampus (HP),

midbrain (MB), caudate/putamen (CP) and pons/medulla (PM).

Accumulation of 8-oxodG

was chosen as an indicator of DNA damage and activity of DNA

glycosylase was used as an

index of DNA repair.

---------------------------------

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reduced mitochondrail function causes ageing

http://www.eurekalert.org/pub_releases/2004-05/src-rmf052704.php

http://sci.tech-archive.net/Archive/sci.med/2004-06/0282.html

V. Sava et al. 3

> INTRODUCTION

>

> http://stinet.dtic.mil/cgi-bin/GetTRDoc?

> AD=A452374 & Location=U2 & doc=GetTRDoc.pdf

>

> Mycotoxins are toxic fungal metabolites which are structurally

> diverse, common

> contaminants of the ingredients of animal feed and human food.

These

> fungal products

> exhibit a range of pharmacological activities that have been

> utilized in development of

> mycotoxins or mycotoxin derivatives as antibiotics, growth

> promoters, and other kinds of

> drugs; still others have been developed as biological and chemical

> warfare agents [1]. Bombs

> and ballistic missiles laden with biological agents including

> aflatoxin were believed to be

> deployed by Iraq during Operation Desert Storm[2]. In light of the

> excess incidence of

> amyotrophic lateral sclerosis in young Gulf War veterans [3], it is

> important not to forget the

> potential neurotoxic effects of low doses of mycotoxins. Although

> much is known about the

> lethal effects of the aflatoxins, little is known about the acute

> and long-term effects of less

> potent mycotoxins, such as Rubratoxin B (RB), on adult nervous

> system.

> Rubratoxin B (RB) is a metabolite of the molds Penicillum rubrum

and

> Penicillum

> purpurogenum. These molds commonly contaminate cereals, foodstuffs

> and grow on damp

> tents and fabrics. RB is not known to produce a serious health

> hazard in this naturally

> occurring form, but pure RB is a bisanhydride lactone with

> hepatotoxic [4] and teratogenic

> properties [5, 6, 7]. Investigation of the effects of acute and

> chronic exposure to RB on the

> nervous system has been scarce, even though neuronal tissue appears

> to be very susceptible to

> the deleterious effect of RB in teratogenic studies [8].

> RB has numerous biochemical actions including the inhibition of

(Na+-

> K+)-ATPase

> [9], inhibition of the hepatic cytochrome P-450-dependent

> monooxygenase system[10],

> reduction of hepatic and renal nonprotein sulfhydryl content [11]

> and inhibition of gap

> junctional intercellular communication [12]. It was found that RB

> caused shifts in the

> V. Sava et al. 4

> ultraviolet absorption spectra of DNA and RNA [13]. The observed

> binding properties of RB

> can disrupt the integrity of DNA and RNA. RB has been shown to

> induce apoptosis [14, 15]

> and internucleosomal fragmentation of DNA [14].

> Studies with isolated mouse liver mitochondria revealed that RB

> disrupted

> mitochondrial respiration and depressed oxygen consumption[8]. The

> principal site of action

> of RB in the mitochondrial electron transport system was found to

be

> between cytochrome C1

> and the termination of electron flow [8]. Ochratoxin, a related

> mycotoxin, has been

> reported to alter mitochondrial respiration and oxidative

> phosphorylation through impairment

> of the mitochondrial membrane and inhibition of the succinate-

> dependent electron transfer

> activities of the respiratory chain [16].

> The overall objective was to study RB neurotoxicity in the context

> of oxidative stress

> induced by inhibition of mitochondrial electron transport in brain

> tissues. Inhibition of

> oxidative phosphorylation would be expected to result in increased

> generation of oxyradicals

> and decreased production of ATP[17]. We hypothesized that RB-

> induced alteration of

> oxidative processes would not be homogeneous across all brain

> regions but would reflect the

> capacity of distinct brain regions to upregulate anti-oxidative

> mechanisms and repair

> processes. Parameters of oxidative stress measured included lipid

> peroxidation

> (thiobarbituric acid-reactive substances or TBARS), SOD activity,

> oxidative DNA damage

> and repair in each of six brain regions cerebellum (CB), cortex

> (CX), hippocampus (HP),

> midbrain (MB), caudate/putamen (CP) and pons/medulla (PM).

> Accumulation of 8-oxodG

> was chosen as an indicator of DNA damage and activity of DNA

> glycosylase was used as an

> index of DNA repair.

>

>

>

>

>

>

> ---------------------------------

> Ahhh...imagining that irresistible " new car " smell?

> Check outnew cars at Autos.

>

>