Presented By Duquesne Marilyn - PowerPoint Presentation

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Presented By

Duquesne MarilynBelgium

3rd International Conference and Exhibition on Traditional & Alternative MedicineAugust 03-05, 2015 Birmingham, UK 

In A

ssociation with

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IntroductionPurpose of the researchMethodResultsConclusion

Herbal remedies : Natural but

not

unhazardous

Study cases

of

Aristolochic

Acid intoxication

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Introduction

Herbal remedies : natural but not unhazardous. Study cases of AA intoxication Introduction 2

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Common termMixture of :

Aristolochic

Acid I (AAI)

Aristolochic

Acid II (AAII)

&

nitrophenantrene

carboxylic acid derivatives

What’s

Aristolochic Acid ?

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

3

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Produced by :

Aristolochia

Asarum

www.fr-academic.ru

Bragantia

www.afleurdepau.com

etc.usf.edu

What’s

Aristolochic

Acid ?

Aristolochiaceae

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

4

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found in :

>

>

>

What’s Aristolochic Acid ?

Medicinal

properties

of

Aristolochia

Rhizomes

: Gastric stimulantFevers treatmentMalaria Roots:Type 2 diabetesSnakebites

Leaves : Skin disordersDyspepsia Leishmania Stems:Anti-inflammatoryDiureticCirculation stimulating

Fruits : Respiratory diseasesSkin woundsMalaria Seeds:BiliousnessAbdominal pain

Flowers : DiureticHypoglycaemic effect

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

5

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Aristolochic

acid toxicity

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

6

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Tubular atrophy

Interstitial fibrosis

Low

molecular

weight

proteinuria

I) Nephrotoxicity

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

7

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I)

Nephrotoxicity

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

8

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II)

Carcinogenicity

Induced by metabolisation of AA

Aristolochic acid I/II

Aristolactam

nitronium ion

R

NQO1

CYP1A1

CYP1A2

NQ

O1

COX

CPR

Adenine

Guanine

R

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

9

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II) Carcinogenicity

Properties of AA-DNA adducts

Cortex

Medulla

Localisation:

Responsible

for:

TP53

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

10

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TP53

Histochemistry

Genomic

Proteomic

Metabonomic

α

-1µglob.

β

-2

µ

glob

.

α

-2

glycoprot

.

INVASIVE

METHOD

+

- NON INVASIVE

METHOD

INVASIVE

METHOD

- NON INVASIVEMETHOD

- EARLY !!

- LATE

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

11

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Balkan Endemic Nephropathy (BEN)Chronic Kidney disease

13

Pr.

Grollman

(thepoisongarden.co.uk)

Etiology:Dietary intoxication

Diseased or suspects : 25000 At risks : >100000

Herbal remedies : natural but

not

unhazardous

. Study cases of AA intoxication

Introduction

12

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Purpose of research

Metabonomic

Mechanism

of

toxicity

Exposure

Absorption

Distribution

metabolism

Primary

target

Target

cell

damage

Target

organ

Damage to

organism

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Purpose

of

research

13

BEN

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Metabonomic procedure

Method :

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Method 14

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What’s

Metabonomic

?

Metabolites

portrait

Mass spectrometry

NMR

Temporal changes

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Method 15

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Samples

collection & preparation

4°C

Antibacterial

Phosphate

buffer

E

xternal

Reference (TSP)

Metabonomic

procedure

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Method 16

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Metabonomic procedure

Spectroscopic

analysisNMR

Proton

electron

Magnetic

field

Z

Y

X

O

Bo

RF

Time

Intensity

Fourier

transform

Frequency

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Method 17

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Spectroscopic

analysis

Spectrum

treatment

&Multivariate analysis

Metabonomic procedure

PC1

PC2

SCORES plot

PC1

PC2

3.40

2.50

1.24

3.80

5.70

3.24

0.80

Observations

Variables

PC1

LOADINGS plot

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Method 18

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Spectroscopic

analysis

Spectrum

treatment

&

Multivariate analysis

Biological interpretation

Metabonomic

procedure

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA intoxication;

Method 19

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Acute

toxicity

Chronic

toxicity

Diseased

Suspects At risks

Herbal remedies : natural but not unhazardous. Study cases of AA intoxication Results 20

Results

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Physiological

data

AAIAAI/AAIIAAIAAI/AAIIAAIAAI/AAIIBody WeightFood intakeWater intakeUrinary volume+ +N.D++ +- --++ ++N.D++ +- - -- --N.D--- - + + + - - - -- - - - - +

Clinical chemistryAAIAAI/AAIIAAIAAI/AAIIAAIAAI/AAIIBUNSr. Creatinine Albumin≠≠≠+ + +++≠+ ++≠+ + + ++++≠+ ++≠+ + + + +++≠

50mg/kg75mg/kg100mg/kg

↘

 

Polyuria

↗↗

↗

75

100

AAII

- - - - -

- - - -

- - - - -

- - - -

+ + + +

+++≠+ + + + + + +≠

Toxicity : AAI < AAI/AAII

 ? AAII ?

Results AA acute toxicityI) Physiological Parameters

AAI

AAI/AAIIAAIAAI/AAIIAAIAAI/AAII

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

: Acute

toxicity

(rats) 21

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A

50 mg/kg AAIB 75 mg/kg AAIC 100 mg/kg AAID 50 mg/kg AAI/AAIIE 75 mg/kg AAI/AAIIF 100 mg/kg AAI/AAII

Results

AA acute

toxicity

I

) Metabonomic results

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

: Acute

toxicity

(rats) 22

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H

ippurate

Glucose

Betaine

Osmoprotectants

Lactate

&

acetate

Results

AA acute

toxicity

I

)

Metabonomic results

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

: Acute

toxicity

(rats) 23

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↘ Hippurate

↗ Glucose

G

lomerulus

Proximal

tubule

Distal

tubule

↘ Cycle Krebs components

↗

Osmoprotectants

↗

Betaine

↗ Lactate &

acetate

Results AA acute toxicityBiological interpretation

Cortex

Medulla

↗↗

Bun

↗

Ser. Creat.

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

: Acute

toxicity

(rats) 24

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↗ Nitrogenous waste in blood↗ Osmoprotectants in urine

Plasma

↘

Reabs

. Glucose

AA

Hippurate

Results

AA acute toxicityBiological interpretation

OAT1

↘

Hippurate

Deficient

cycle Krebs

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

: Acute

toxicity

(rats) 25

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Metabonomic

profile

reflecting the severity of renal damage in proximal tubules and/or interstitial tissue: Psihogios, N ; Kalaitzidis, R ; Dimou, S ; Seferiadis,K ; Siamopoulos, K ; and Bairaktari, E. Evaluation of Tubulointerstitial lesions severity in patients with glomerulonephritides : An NMR-based metabonomic study. J.Proteome Res. 2007, 6, 3760-3770

Results AA chronic toxicity

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

:

Chronic

toxicity

(

Humans

) 26

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Creatinine

filtration : V

Hippurate

secretion

: VGlucose reabsorption : V

Creatinine filtration : XHippurate secretion: XGlucose reabsorption : X

Metabonomic profile : Healthy

Creatinine

filtration : XHippurate secretion : XGlucose reabsorption : V

Metabonomic profile:Moderate renal injury

Metabonomic profile:Severe renal injury

Metabonomic comparison diseased, suspects, at risks, others , NEN with Belgium control samples.

Metabonomics

: on the Road to Detect Diagnostic Biomarkers in Endemic (Balkan) Nephropathy. Evaluation in a Retrospective Pilot Project. Duquesne et al., J Cancer Sci Ther 2012

Results AA chronic toxicity

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

:

Chronic

toxicity

(

Humans

) 27

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H

ealthy

Moderate

renal injurySevere renal injury

Comparison of the different metabonomic profiles : healthy , moderale and severe renal injury

Renal damage severity

Results AA chronic toxicity

Herbal remedies : natural

bu

t not

unhazardous

. Study cases of AA

intoxication

Results

:

Chronic

toxicity

(

Humans

) 28

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Perspectives & Conclusions

Acute toxicity model

Chronic toxicity model

In process

Metabolites

identification

:

early & easily biomarkers ( ↗ Glucose, betaine, osmoprotectants ; ↘ hippurate, cycle Krebs components )

New

samples

BEN

Biological

hypotheses

(

renal

functions

, transport injuries,…)

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Perspectives & Conclusion

Metabonomic

- NON INVASIVE

METHOD

- EARLY

Biomarkers

Lab.

Human

Biology

&

Toxicology

UMONS

(

Belgium

)

High

possibility

of human AA intoxication cases

!!

Preventive

action

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Duquesne Marilyn

PhD student

Human

Biology &

Toxicology

laboratory

University

of Mons(Belgium)

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Profile :  Familial history  Proteinuria :  ACR, alpha-1  Azotemia   (serum creatinine)  anemia  15 years in EN  Diseased  v  v  v  v    v  v    v  v    v  v  v  v  Suspects  v  v          v    v    At risks  v          Others :  x  x  x  x    

 

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http://biology-igcse.weebly.com/dialysis.htmlhttp://www.nuhospitals.com/renal-kidney-transplant.htmlhttps://sites.google.com/a/montessori.edu.co/biology-projects/dna-vocabulary-2/_draft_post-12http://www.medicinenet.com/kidney_infection/article.htmhttp://carcin.oxfordjournals.org/content/24/10/1695/F1.large.jpghttp://www.google.be/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=&url=http%3A%2F%2Fwww.ayurvedindia.in%2FOthers%2FLiver-Disorders%2F961&ei=inE3VeL7GdbsaMyxgYAE&psig=AFQjCNFvJDXErveYz2GG_VmWaQIoHQKqeA&ust=1429783307048964https://www.flickr.com/photos/14179358@N05/3678083407/WWW.stjude.comtutocours.frwww.michigananimalhospital.comwww.vcahospitals.comwww.riversideonline.comwww.mhhe.comhyperphysics.phy-astr.gsu.edu

Herbal remedies : natural but unhazardous. Study cases of AA intoxication ; Introduction

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Meet the eminent gathering once again atTraditional Medicine-2016London, UKOctober 03-05, 2016

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