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INFLUENCE OF MELATONIN ON ARSENIC MEDIATED PANCREATIC DAMAGE IN SWISS ALBINO MICE DIMPLE DAMORE Bhavan’s Sheth R.A.College of Science, Gujarat University,

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Presentation on theme: "INFLUENCE OF MELATONIN ON ARSENIC MEDIATED PANCREATIC DAMAGE IN SWISS ALBINO MICE DIMPLE DAMORE Bhavan’s Sheth R.A.College of Science, Gujarat University,"— Presentation transcript:

1 INFLUENCE OF MELATONIN ON ARSENIC MEDIATED PANCREATIC DAMAGE IN SWISS ALBINO MICE
DIMPLE DAMORE Bhavan’s Sheth R.A.College of Science, Gujarat University, Ahmedabad, Gujarat, India

2 INTRODUCTION Arsenic - 20th most abundant element
Arsenic toxicity - global health problem affecting millions of people Arsenic Contamination in the world – US, Mexico, Chile, Bolivia, Argentina, Hungary, Romania, India, Bangladesh, Thailand, Vietnam, Taiwan, China Nepal Asia - Bangladesh, Taiwan and India (West Bengal)

3 ARSENIC CONTAMINATION IN THE WORLD

4 CONTAMINATION Natural geological sources Mining Industrial processes Commercial products Pesticides, Herbicides, Fungicides Food - Seafood & Fish

5 Absorption - predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation Absorbed arsenic accumulates in the liver, pancreas, kidney, heart, and lungs and deposited in the keratin rich tissues: nails, hair, and skin.

6 EFFECTS Gastrointestinal Renal Dermal Haematological
Developmental Musculoskeletal Reproductive Endocrine Respiratory Neurological Cardiovascular Hepatic

7 HALLMARK SIGNS OF ARSENIC TOXICITY skin lesions on palm , blackfoot disease

8 ARSENIC TOXICITY Formation of ROS/RNS, Alter sulfhydryl homeostasis
Lipid peroxidation Conformational changes to biomolecules DNA damage Depletion of glutathione Carcinogenicity of Lung, Skin, Kidney, Liver, Bladder, GI tract

9 Antioxidants used to combact Arsenic toxicity
Vitamins A, C, D & E Calcium Supplementation Protein Supplementation Combination of Vitamins and Calcium Selenium Antioxidants like SOD, GSH, Catalase Amino acids ( Methionine, Cystine & Cysteine Plant Extracts ( Curcumin & Kalmegh-Andrographis paniculata) Antioxidant Used in this study - Melatonin

10 MELATONIN (5-methoxy-N-acetyl tryptamine)

11 MELATONIN (MLT) Regulation of retinal function, Circadian rhythm, Reproduction Oncostatic effects Anti inflammatory functions Immune system stimulations Powerful antioxidant

12 MELATONIN (MLT) Direct free radical scavenger Detoxifies ROS/RNS
Stimulation of antioxidant enzymes Augmenting the efficiency of other antioxidants Increasing the efficiency of mitochondrial oxidative phosphorylation and reduces electron leakage there by lowers free radical generation

13 OBJECTIVES : IN VIVO STUDIES
To study the effect of arsenic trioxide (As2O3) on biochemical parameters, serum indices & histological analysis of Pancreas To investigate the ameliorative effect of melatonin (MLT) on arsenic induced pancreatitis

14 EXPERIMENTAL PROTOCOL
Animals : Adult Swiss Female Mice. (Mus musculus) (30-35g) Experimental Groups : Control As2O3 treated (LD – 0.5mg/kg bw ) As2O3 treated (HD – 1.0mg/kg bw) Melatonin (MLT) alone As2O3 (HD) + MLT Mode of administration : As2O3 (po) and MLT (ip) Duration of Treatment : 30 days

15 PARAMETERS STUDIED Gravimetric : Body weight & organ weight
Biochemical : Protein (Lowry et al., 1951) Total –SH ( Sedlak & Lindsay., 1968 ) Blood Glucose (Nelson & Somogyi., 1945) Serum Amylase (Schwiara., 1972) Serum Lipase (Moss & Henderson., 1999) Arsenic Retention Estimation STATISTICAL ANALYSIS

16 General Mechanism of Arsenic Induced Toxicity
As - High affinity for –SH groups –Protein degradation ↓ Carbohydrate metabolism ↓ Enzymes - ROS/Radicals/H2O 2 - ↓ Antioxidant system – ↑ LPO Oxidative Stress – Protein degradation - Accumulation in mitochondria - ↓ Carbohydrate metabolism ↓ Enzymes – Metabolic Insult - Pancreatitis

17 GRAVIMETRIC

18 PROTEIN & TOTAL -SH

19 SERUM AMYLASE BLOOD GLUCOSE

20 SERUM LIPASE

21 HISTOPATHOLOGICAL ANALYSIS
CONTROL Normal architecture of Pancreas Normal Islet size & cell population Normal acinar tissue Normal capillary number in Islet ARSENIC TREATED (Pathological changes ) Shrunken islets with vacuolization Reduction in Islet cell number Damaged acinar tissue Increased capillary number & diameter

22 T.S of pancreas of MLT+ As2O3 treated mouse showing revival in the morphology and population of cells

23 CONCLUSION Arsenic trioxide treatment
- Reduction in body and organ weights - Declined levels of protein and total sulfhydryl groups - Elevated levels of serum amylase, serum lipase & blood glucose - Arsenic retention Histological analysis - Destruction of the exocrine and endocrine tissue

24 Administration of melatonin (MLT)
Reversed the above toxic effects and improved the arsenic induced altered function in pancreas

25 PROBABLE MECHANISM BY WHICH MELATONIN
PROTECTS AGAINST ARSENIC TOXICITY MELATONIN (MLT) quenches superoxide radical Suppresses NO formation Attenuates Accumulation of H2O2 Prevents ROS formation Protective effects in activities of antioxidant system Oxidative Stress

26 Thank you

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