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Biomarkers for environmental
toxicologyPRESENTED BY -MOHAMMAD ANASDBT-JRFCSIR-IITR
Biomarkers : definition
“A characterstic that is objectively measured and evaluated as an indicator
of normal biological processes, pathogenic processes or
pharmacological responses to a therapeutic intervention”
- NIH
Development of biomarkers
Cherry red colour• CO poisoning
Kayser- fliecher ring• Wilson’s disease
Lead lines in gums• Pb toxicity
Cholinesterase• Organophosphate poisoning
Biomarkers in toxicological studies
Biomarker of Exposure
Biomarker of Effect
Biomarker of Susceptibility
Eg. Methyl Hg Eg. Paraoxonase
Eg. Metallothionein
Stages of toxic phenomenon and timing of three types of biomarkers
Phase I:Exposure and
Absorption
Phase II:Distribution
and metabolism
Phase III:Interaction with
endogenous macromolecules
Phase IV:Early
Subclinical changes
Phase V : Clinical signs
Biomarkers of susceptibility
Biomarkers of effect (response)
Biomarkers of exposure
Aldridge, N. (2001) Stages in the induction of toxicology. Mechanisms and Concepts in Toxicology.
Requirements of a good biomarker in toxicological testing
Biomarker requirements
Easy chemical analysis
Simplicity for sampling
Ethically acceptable
Relevancy
Reflect a reversible change
Validity
Some examples of biomarkers used in environmental toxicology
Biomarkers
1-hydroxypyrene
Blood Pb
Methyl HgMetallothionein
Cotinine
Metallothionein : biomarker for heavy metal contamination
Heavy Metals
Non essentialBa, Li, Zr
Less toxicSn, Al
Highly toxicPb, Hg, Cd,
As
Essential Cu, Zn, Co, Cr, Mn, Fe
On health effects basis
Metal having atomic weight greater than sodium (23) and specific gravity (density) > 5gm/cm3
(Mukesh K. Raikwar et al.,2008)
Heavy metal toxicity in fishes
• Loss of equilibrium• Increased operculum movement• Irregular vertical movements Cd, Pb, Hg and As – - Severe renal and nervous system damage - Gill damage
Lamellar telanejctasis
Lamellar necrosis
Global Veterinaria 12 (2): 219-231, 2014 ISSN 1992-6197 © IDOSI Publications, 2014
Metallothionein
• Synthesized in reponse to elevated heavy metal concentrations.
• Strong affinity to bind many metal cations – As, Cd, Cu, Pb, and Hg
• Reported in about 50 different aquatic invertebrates from 5 phyla.
Nordberg, M., and Nordberg, G.F. (2000) Toxicological aspects of metallothionein.
Rohu Katla Mrigel0
5
10
15
20
25
30
35
Umcontaminated
Contaminated
GillGill
Rohu Katla Mrigel0
510
1520253035
404550
Uncontaminated
Contaminated
Liver
Rohu Katla Mrigel0
5
10
15
20
25
30
35
Uncontaminatedcontaminated
Muscle
Heavy metal decreases total protein concentration in fishes
Environmental Research, Engineering and Management, 2011.
Liver
MuscleMuscle
Gill
Muscle Liver Gill
ROHU KATLA MRIGEL0
10
20
30
40
50
60
70
80
Uncontaminated
Contaminated
Muscle
ROHU KATLA MRIGEL0
5
10
15
20
25
30
UncontaminatedContaminated
Met
allo
thio
nein
con
c. µ
g/g
ww Gill
ROHU KATLA MRIGEL0
50
100
150
200
250
UncontaminatedContaminated
Liver
Heavy metal increases Metallothionein concentration in fishes
Environmental Research, Engineering and Management, 2011.
Methyl mercury : A biomarker of exposure
Hg – in emissions (smoke)
50-75% from anthropogenic (human) sources
Hg - Deposited on land and into water
Methyl-mercury (MeHg)
Bacteria
Phytoplankton (algae)
MeHg
Zooplankton
MeHg
MeHg MeHg
Small fishLarge fish
Me-Hg : Gets in the food web
Methyl-Hg poisoning
• Methyl-Hg exposure causes neurotoxic effects- - Paraesthesia - Ataxia - Visual and hearing loss• Children more vulnerable to Me-Hg toxicity than adults.• Minimata disease in Japan.
Jakubowski and Trzcinka-Ochocka, 2005
Me-Hg as a biomarker of exposure
• High levels of Hg acts as a biomarker of exposure to Methyl-Hg• Biological sample – Hair, nail, blood, urine• Normal Hg level - Non fish eating individuals - < 1 μg/g Fish eating individuals - > 30 μg/g • Mercury level in maternal hair - 70 μg/g ---- 30 % risk in children 10 – 20 μg/g ---- 5% risk in children
• Detection by Atomic Absorption Spectroscopy.
Jakubowski and Trzcinka-Ochocka, 2005
Summary
• There is a need for combining data from multiple biomarkers.
• Environmental toxicology has benefitted with the use of biomarkers.
• Biomarkers range from very simple to complex ones.
• Methyl-Hg and Metallothionein are some examples of biomarkers.
Future perspective
• Biomarkers can provide valuable predictive tools in biomonitoring and ecological risk assessment.
• Important role in the model for 21st Century Toxicology – “ Toxicity testing in the 21st Century : A Vision and Strategy.” -(NAS 2007)
• Continued research in validation of biomarkers and use of highthroughput technology.
Acknowledgements
• AcSIR 2015 batchmates• DBT
Thank You