CHEMOPROTECTIVE ROLES OF DIPHENYL DISELENIDE(DPDS) ON CHLORPYRIFOS(CPF)- INDUCED NEUROTOXICITY IN MID-BRAIN OF MALE RATS

Adeigbe Victor 87 PAGES (16227 WORDS) Article
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ABSRACT

Chlorpyrifos [CPF; O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphorothionate] is a widely used organophosphate pesticide that is known to be toxic to the environment and to living beings. It affects several organs of the body especially the brain leading to impairment of normal functioning of the body. Diphenyl diselenide (DPDS), an organsoselenium compound is the simplest of the synthetic diaryldiselenides. Studies have shown that DPDS exhibits anti-inflammatory and antioxidant effects if administered in pharmacological doses. This present study was aimed at investigating the neurotoxic effects of CPF on the midbrain of male Wistar rats and the possible counter effects by DPDS.


This project work was carried out using a total of sixty (60) male Wistar rats which were grouped into five cages of twelve rats each. The animals underwent acclimatization before being treated for 5 weeks. Group A rats were given corn-oil as control; Group B rats received DPDS (5mg/kg) only dissolved in corn-oil; Group C rats were treated with CPF (5mg/kg) only dissolved in corn-oil; Group D rats were co-exposed to CPF (5mg/kg) + DPDS (2.5mg/kg) while Group E rats were co-exposed to CPF (5mg/kg) + DPDS (5mg/kg) for the whole of the 5 weeks after which they were euthanized. The mid-brain was excised, homogenized and centrifuged. Markers of brain oxidative damage and histopathology were evaluated in the rats.


Superoxide dismutase (SOD) activity, catalase (CAT) activity, reduced glutathione (GSH) level, Glutathione Peroxidase (GPx) activity, glutathione-S-transferase (GST) activity and acetylcholinesterase (AChE) activity were significantly(p < 0.05) reduced in the mid-brain of the rats treated with chlorpyrifos (CPF) alone as compared to the control rats. Also, oxidative and inflammatory markers such as hydrogen peroxide (H2O2) level, lipid peroxidation (LPO) and myeloperoxidase (MPO) activity respectively were significantly increased in the same rats. However, the co-exposure with DPDS ameliorated the neurotoxic effects of CPF by increasing the antioxidant level and suppressing the oxidative stress biomarkers. Also, the weights of the midbrain of rats treated with CPF showed no significant change.


Summarily, DPDS reversed the neurotoxic effects in midbrain induced by CPF via the antioxidant and anti-inflammatory properties which it possesses. 

TABLE OF CONTENTS
Title page i
Certification ii
Dedication iii
Acknowledgements iv
Table of contents v
List of figures ix
List of tables x
Abstract xi

CHAPTER ONE: INTRODUCTION AND LITERATURE REVIEW
1.1                   Introduction 1
1.1.1             Aim of study 4
1.1.2             Objectives of the study 4
1.2                   Literature review 5
1.2.1             The Nervous system 5
1.2.2             The Brain 6
1.2.3             Structure and function of the brain 7
1.2.3.1             The Brain stem 7
1.2.3.2             Cerebrum 8
1.2.3.3             Cerebellum 9
1.2.3.4 Hypothalamus 9
1.2.3.5             Thalamus 9
1.2.4             Chlorpyrifos (CPF) 10
1.2.4.1             Neurological effects of CPF 11
1.2.5             Physical and Chemical properties 11
1.2.6             Toxicity of CPF 12
1.2.7             Mechanism of action 13
1.2.8             Selenium 14
1.2.9             Diphenyl Diselenide (DPDS) 14
1.2.9.1 Antioxidant action of DPDS 15
1.2.9.2 Neuroprotective effects of DPDS 16
1.2.9.3 Anti-inflammatory activity of DPDS 16
1.2.10 Reactive oxygen species and free radicals 17
1.2.10.1 Superoxide anion 19
1.2.10.2 Hydrogen peroxide 20
1.2.10.3 Hydroxyl radical 20
1.2.10.4 Singlet oxygen 21
1.2.11             Oxidative stress 21
1.2.11.1 Lipid peroxidation 21
1.2.11.2 Protein oxidation 23
1.2.11.3 DNA damage 24
1.2.12             Antioxidant system 24
1.2.12.1 Antioxidant enzymes 25
1.2.12.2 Non-enzymatic antioxidants 27
 
CHAPTER TWO: MATERIALS AND METHODS
2.1 Chemicals 29
2.2 Experimental animals 29
2.3 Experimental design and treatment 29
2.4 Sacrifice of experimental animals 30
2.5 Homogenization 30
2.6 Reagents preparation 31
2.7 Biochemical assays 31
2.7.1 Determination of protein concentration 31
2.7.2 Determination of catalase 34
2.7.3 Assessment of lipid peroxidation 35
2.7.4 Estimation of reduced Glutathione GSH level 37
2.7.5 Determination of superoxide dismutase SOD activity 41
2.7.6 Determination of Hydrogen peroxide concentration 42
2.7.7 Estimation of Glutathione-S-Transferase activity 46
2.7.8 Assay for Glutathione peroxidase activity 47
2.7.9 Measurement of Myeloperoxidase activity 49
2.7.10 Determination of Acetylcholinesterase activity 51
2.8 Histopathology 53
2.9 Statistical analysis 53



CHAPTER THREE: RESULTS
3.1 Weight analysis 54
3.2 Biochemical analysis 56
3.3 Histopathological assessment 65

CHAPTER FOUR: DISCUSSION AND CONCLUSION
4.1 Discussion and Conclusion 66

References 70



















LIST OF FIGURES
Figure 1.1 Anatomy of the Brain 7
Figure 1.2 Structure of Chlorpyrifos 10
Figure 1.3 Structure of Diphenyl diselenide 14
Figure 2.1 Standard curve for protein determination by Bradford’s method 33
Figure 2.2 MDA reaction in Lipid Peroxidation assay 35
Figure 2.3 Reaction of reduced GSH with Ellman’s Reagent    37
Figure 2.4 GSH Standard curve 40
Figure 2.5 Calibration curve for Hydrogen Peroxide 45
Figure 3.1 Histopathogical photomicograph 65


















LIST OF TABLES
Table 1.1 Physical and chemical properties of Chlorpyrifos 11
Table 1.2 Clinical conditions involving reactive oxygen species 18
Table 2.1 GSH Standard Curve Protocol 39
Table 2.2 Preparation of H2O2 standard curve 43
Table 2.3 Glutathione-S-Transferase Assay Medium 47
Table 2.4 Protocol for Acetylcholinesterase activity 52
Table 3.1 Body weight change of male rats treated with CPF and DPDS 54
Table 3.2 Brain weight change of male rats treated with CPF and DPDS 55
Table 3.3 GPx activity in mid-brain of male rats treated with CPF and DPDS 56
Table 3.4 LPO level in mid-brain of male rats treated with CPF and DPDS 57
Table 3.5 CAT activity in mid-brain of male rats treated with CPF and DPDS 58
Table 3.6 SOD activity in mid-brain of male rats treated with CPF and DPDS 59
Table 3.7 GSH level in mid-brain of male rats treated with CPF and DPDS 60
Table 3.8 GST activity in mid-brain of male rats treated with CPF and DPDS 61
Table 3.9 H2O2 level in mid-brain of male rats treated with CPF and DPDS 62
Table 3.10 MPO activity in mid-brain of male rats treated with CPF and DPDS 63
Table 3.11 AChE activity in mid-brain of male rats treated with CPF and DPDS 64


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APA

Adeigbe, V (2020). CHEMOPROTECTIVE ROLES OF DIPHENYL DISELENIDE(DPDS) ON CHLORPYRIFOS(CPF)- INDUCED NEUROTOXICITY IN MID-BRAIN OF MALE RATS. Afribary.com: Retrieved November 27, 2020, from https://afribary.com/works/adeigbe-victors-project-work-feb-2018

MLA 8th

Victor, Adeigbe. "CHEMOPROTECTIVE ROLES OF DIPHENYL DISELENIDE(DPDS) ON CHLORPYRIFOS(CPF)- INDUCED NEUROTOXICITY IN MID-BRAIN OF MALE RATS" Afribary.com. Afribary.com, 18 Jun. 2020, https://afribary.com/works/adeigbe-victors-project-work-feb-2018 . Accessed 27 Nov. 2020.

MLA7

Victor, Adeigbe. "CHEMOPROTECTIVE ROLES OF DIPHENYL DISELENIDE(DPDS) ON CHLORPYRIFOS(CPF)- INDUCED NEUROTOXICITY IN MID-BRAIN OF MALE RATS". Afribary.com, Afribary.com, 18 Jun. 2020. Web. 27 Nov. 2020. < https://afribary.com/works/adeigbe-victors-project-work-feb-2018 >.

Chicago

Victor, Adeigbe. "CHEMOPROTECTIVE ROLES OF DIPHENYL DISELENIDE(DPDS) ON CHLORPYRIFOS(CPF)- INDUCED NEUROTOXICITY IN MID-BRAIN OF MALE RATS" Afribary.com (2020). Accessed November 27, 2020. https://afribary.com/works/adeigbe-victors-project-work-feb-2018