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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 199-208

Neuroprotective effect of phoenix dactylifera (date palm) on paraquat triggered cortico-nigral neurotoxicity


1 Department of Human Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Ahmadu Bello University (ABU); Neuroanatomy and Neurosciences Research Unit, Department of Human Anatomy, ABU, Zaria, Nigeria
2 Department of Human Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Ahmadu Bello University (ABU); Microscopy and Stereology Research Unit, Department of Human Anatomy, ABU; Neuroanatomy and Neurosciences Research Unit, Department of Human Anatomy, ABU, Zaria, Nigeria
3 Department of Human Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Ahmadu Bello University (ABU); Microscopy and Stereology Research Unit, Department of Human Anatomy, ABU, Zaria, Nigeria

Date of Submission04-Jun-2021
Date of Decision23-Nov-2021
Date of Acceptance30-Nov-2021
Date of Web Publication27-Dec-2021

Correspondence Address:
Gbenga Peter Oderinde
Department of Human Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Kaduna
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnbs.jnbs_28_21

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  Abstract 


Background: Herbicides including paraquat (PQ) have been reported to have deleterious effects on biological systems and normal functioning of the brain, especially regions related to motor functionality and coordination like the cerebrum and substantia nigra resulting in neurodegenerative conditions such as Parkinson's disease. Phoenix dactylifera has high nutritional value and is beneficial in the management and treatment of diverse ailments. Aim: This study assessed the protective properties of Aqueous fruit extract of P. dactylifera (AFPD) on PQ-triggered cortico-nigral neurotoxicity in rats. Neuroprotective properties of AFPD were assessed using beam walking performance (BWP) for motor coordination, oxidative stress biomarkers (Malondialdehyde [MDA], superoxide dismutase [SOD], and glutathione [GSH]) and histological examination (H and E stained) for cytoarchitectural changes. BWP across the study period revealed no motor coordination deficit with PQ exposure. Materials and Methods: Twenty-five rats were categorized into five groups (n = 5); the control was administered 2 ml/kg distilled H2O, another group received 11.35 mg/kg PQ, another received 11.35 mg/kg PQ + 10 mg/kg L-dopa as reference drug, while two other groups received 11.35 mg/kg PQ + 500 mg/kg AFPD and 11.35 mg/kg PQ + 1,000 mg/kg AFPD, respectively, for 28 days. Results: PQ-treated group revealed oxidative stress by significant elevation of MDA levels and decrease in antioxidant enzymes (SOD and GSH). Remarkable cytoarchitectural distortions were observed with PQ treatment. However, AFPD treatment showed ameliorative properties by a significant decrease in MDA levels and increased SOD and GSH activities. Mild distortion-to-relatively normal neuronal cytoarchitecture relative to the control was also observed with AFPD treatment. Conclusion: AFPD possesses potential neuroprotective properties against PQ-triggered pathological changes in cortico-nigral structures of Wistar rats.

Keywords: Beam walking performance, cytoarchitecture, motor coordination, neurodegeneration, oxidative stress


How to cite this article:
Edobor HD, Musa SA, Umana UE, Oderinde GP, Agbon AN. Neuroprotective effect of phoenix dactylifera (date palm) on paraquat triggered cortico-nigral neurotoxicity. J Neurobehav Sci 2021;8:199-208

How to cite this URL:
Edobor HD, Musa SA, Umana UE, Oderinde GP, Agbon AN. Neuroprotective effect of phoenix dactylifera (date palm) on paraquat triggered cortico-nigral neurotoxicity. J Neurobehav Sci [serial online] 2021 [cited 2022 Jan 17];8:199-208. Available from: http://www.jnbsjournal.com/text.asp?2021/8/3/199/333757




  Introduction Top


Exposure to environmentally based substances including chemicals, heavy metals and herbicides have been documented to have lethal effects on the health status and normal brain functioning of humans and animals.[1],[2],[3],[4] Agrochemicals, especially those used as weed control are a major hazard challenge in some nations of the world. Paraquat (PQ) is considered to be among the main herbicide involved in intentional and accidental poisoning and is responsible for a high rate of illnesses including alteration of normal biological functions and neurological disease conditions.[5],[6],[7] PQ causes toxicity in vital regions of the brain including cerebrum and substantial nigra that play a critical role in motor coordination, supporting the idea that exposure to this herbicide may contribute to the pathophysiology of neurodegenerative diseases like Parkinson's disease (PD).[8],[9],[10] Protein aggregation, mitochondrial dysfunction, altered dopamine levels, and increased oxidative stress are majorly reported mechanisms by which PQ causes neurological disease conditions.[11],[12],[13]

Cerebral cortex (CC) is an imperative part of the brain responsible for the execution of higher-order cerebral functions, including cognition, sensory perception, and motor control,[14] with multiple functions connected to different brain parts.[15],[16] Substantia nigra (SN), a neuronal structure located in the ventral midbrain, with vital connections with CC (cortico-nigral pathway) exerts regulatory function within the basal ganglia circuitry.[17] SN is involved in several neurological and neuropsychiatric disorders.[17],[18],[19] Secondary damage to SN has been associated with cerebral infarction with the development of sustained dementia, PD, and poor neurofunctional outcomes.[19],[20],[21]

Date palm (Phoenix dactylifera) is one of the members of the palm family Arecaceae.[22] There have been several reports of the high nutritional value of P. dactylifera and, properties that acknowledged it as potential nutraceutical agents.[23],[24] Dates and their constituents are useful in the prevention and treatment of diverse ailments through antioxidant, anti-inflammatory, and antimicrobial activities.[25] The deleterious effects and health implication of PQ exposure is moderately established, especially the corticonigral structures of the brain in animal models. There is a need to assess the phytotherapeutic potentials of this plant in PQ-induced neurotoxicity. This study assessed the neuroprotective properties of P. dactylifera on PQ-induced corticonigral neurotoxicity in rats.


  Materials and Methods Top


This study was performed in line with the principles of the Declaration of Helsinki, as revised in 2013. Ethical clearance for this study was provided by the Ethics Committee on Animal Use and Care, Ahmadu Bello University (ABU), Zaria: ABUCAUC/2018/097.

Plant material collection and identification

P. dactylifera L.(date palm) dried fruits were collected in Zaria, Kaduna State, Nigeria. Collected plant material was identified (Voucher Specimen Number: 21104) in the Department of Botany, Faculty of Life Sciences, ABU, Zaria.

Plant material extraction

Date palm fruit pulp was separated from the seed (pit) for preparation of aqueous fruit pulp extract of P. dactylifera (AFPD). Maceration method of extraction as described by Agbon et al.[26] was adopted. Extraction of the fruit pulp was carried out in the Department of Pharmacognosy and Drug Development, Faculty of Pharmaceutical Sciences, ABU, Zaria.

Experimental animals

Apparently healthy adult male Wistar rats (100–150 g) were obtained from the Animal House facility of the Faculty of Pharmaceutical Sciences, ABU, Zaria. The rats were transported to the Animal House, Human Anatomy Department, Faculty of Basic Medical Sciences, ABU, Zaria, housed under standard laboratory conditions, light and dark cycles of 12 h provided and fed with rat chow and water ad libitum and allowed to acclimatize for a period of fourteen (14) days before the commencement of experimentation.

Drugs

Paraquat

PQ (Paracot® PQ Dichloride) was obtained and used as neurotoxin in this study. The product is manufactured by Hubei Xianlong Chemical Industry Co, China.

Levodopa (L-dopa)

Levodopa (Sinemet) tablet was obtained and used as a reference drug to evaluate the therapeutic property of AFPD. The product is manufactured by Mylan Pharmaceuticals, Inc., Morgantown, USA.

Ketamine

Ketamine (Ketamine Hydrochloride injection USP, 50 mg/ml) was obtained and used for anesthesia. The product is manufactured by Swiss Parenterals PVT Ltd, Gujarat, India.

Experimental protocol

Twenty-five (25) rats were categorized into five (5) groups (groups A to E) of five rats each for a twenty-eight (28) day period of treatments via oral route; group A served as the control group, treated with distilled H2O (2 ml/kg), group B was treated with PQ (11.35 mg/kg; 28.4% LD50 oral, Haley, 1979[27]), group C was treated with PQ (11.35 mg/kg) + L-dopa (10 mg/kg), groups D and E were treated with PQ + AFPD (500 mg/kg) and PQ + AFPD (1,000 mg/kg), respectively [Figure 1]. Following experimentation, rats were euthanized using Ketamine (75 kg/mg i. p)[28] anesthesia, the rats were decapitated and skull dissected to remove the brain. Harvested whole brains were dissected sagittally at the midline into two equal halves, one part homogenized for biochemical analysis and the other part fixed in Bouin's fluid for histological processing.
Figure 1: Experimental protocol. N = 5; AFPD = Aqueous fruit pulp extract of Phoenix dactylifera; PQ = Paraquat

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Neurobehavioural study

Neurobehavioral assessment was conducted using beam walking apparatus (BWA). Beam walking test in this study assessed motor coordination and balance by measuring the beam walking performance (BWP) as the rats' ability to traverse a narrow beam to reach a safety platform according to the method described by Perry et al.[29] A modification of BWA described by Carter et al.[30] was adopted.

The BWA consisted of an elevated platform connected by a 100 cm long wood beam with a width of 3 cm. The beam was placed horizontally, 50 cm above the floor surface, with one end mounted on narrow support (connected to start platform 10 cm × 10 cm) and the other end attached to a goal box (20 cm × 20 cm × 20 cm). The start point was placed by a bright light source to motivate the rats to traverse the beam. Protection for falling rats was provided by a sawdust-filled box placed at the base of the platform.

The latency until the rat's nose entered the enclosed safety box (within 60 s) was recorded. Rats that slipped off the beam or could not make their way into the goal box were assigned latencies of 60 s. Beam-walking scores were based on an average of three (3) trials, cleaned with methylated spirit at inter-trial intervals. The rats were habituated to the apparatus for 3 days before treatment. BWP was assessed across the study period (from pretreatment through week four (4) of treatment) and data analyzed statistically.

Biochemical studies

Brains were weighed using digital weighing scale (Acculab Vicon VIC-511 Precision Balance/Scale, USA, 0.001 g) and mechanically homogenized in 0.1 M phosphate buffer (pH 7.4) (1 g tissue/4 ml) according to the method described by Ige et al.[31] Homogenate was analyzed for oxidative stress biomarkers (Malondialdehyde, [MDA]; superoxide dismutase, [SOD] and reduced glutathione, [GSH]). Biochemical analysis was conducted at the Department of Human Anatomy, ABU, Zaria. MDA (thiobarbituric-acid reactive substance) assay estimated lipid peroxidation levels according to the method of Ohkawa et al.[32] Enzymatic antioxidant activity was estimated by assaying SOD activity according to the methods of Fridovich,[33] and GSH activity according to the methods Ellman[34] as described by Rajagopalan et al.[35] Data obtained were subjected to statistical analysis.

Histological studies

Fixed brain samples were processed using histological techniques by making sections to target the cerebrum (layer V: internal pyramidal layer of the CC) and SN using Rats Brain  Atlas More Details as a guide.[36] The tissue sections were examined for histopathological changes using light microscopy (Optical Microscope; HM-LUX, Leitz Wetzlar, Germany) [Figure 2]. Histological paraffin sections were processed and stained with Hematoxylin and Eosin (H and E) stains for demonstration of cytoarchitecture of brain regions of interest in the Histology Unit of the Department of Human Anatomy, ABU, Zaria. Microscopy and micrography (using Digital Microscopic Camera, MA 500 AmScope®, USA) were conducted in the Microscopy and Stereology Research Laboratory of the same facility.
Figure 2: Structures of the cortico-nigral pathway

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Data analysis

Data obtained from this study were expressed as mean ± SEM. One-way analysis of variance was used to compare mean difference between groups followed by Tukey post hoc test. Paired t-test was employed for the comparisons of means as appropriate. Values were considered significant when P < 0.05. Analyses were done using the statistical software, Statistical Package for the Social Sciences (IBM SPSS v21.0, Armonk, NY, USA: IBM Corp).


  Results Top


Neurobehavioural study

Beam walking, oxidative stress, cerebrum, substantia nigra

In this study, BWP was assessed as a pointer to motor coordination and balance. Increased BWP values (latency time to cross the beam) indicate deficit in motor coordination and balance, while decreased BWP values indicate improved functionality.

Results revealed significant (P < 0.05) improvement in BWP in the PQ-treated, control, and PQ + L-dopa-treated groups when latency time to traverse the beam were compared between pre-treatment and week 1 of the experiment [Figure 3]a.
Figure 3: (a) Comparison of beam walking performance (pretreatment and Week 1) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = 0.046, bp = 0.018, cp = 0.002 were the significant difference when pre-treatment (t) was compared with week 1 (WK1). CTL = Control (distilled water 2 ml/kg); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1,000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (b) Comparison of beam walking performance (Pre-treatment and Week 2) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = 0.017, bp = <0.001, cp = 0.049 were the significant difference when pretreatment (t) was compared with week 2 (WK2). CTL = Control (2 ml/kg distilled water); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (c) Comparison of beam walking performance (pretreatment and Week 3) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = <0.001, bp = 0.018, cp = 0.008 were the significant difference when pre-treatment (t) was compared with week 3 (WK3). CTL = Control (distilled water 2ml/kg); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (d) Comparison of beam walking performance (Pre-treatment and Week 4) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = 0.021, bp = 0.040, cp = 0.001, dp = 0.043, ep = 0.028 were the significant difference when pre-treatment (t) was compared with week 4 (WK4). CTL = Control (2 ml/kg distilled water); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera

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Results revealed significant (P < 0.05) improvement in BWP in the PQ-treated and PQ + L-dopa-treated, PQ + AFPD (1000 mg/kg) groups when latency time to traverse the beam were compared between pre-treatment and week 2 of the experiment [Figure 3]b.

Results revealed significant (P < 0.05) improvement in BWP in the PQ-treated, control and PQ + AFPD (500 mg/kg)-treated groups when latency time to traverse the beam were compared between pretreatment and week 3 of the experiment [Figure 3]c.

Results revealed significant (P < 0.05) improvement in BWP in all the groups when latency time to traverse the beam were compared between pretreatment and week 4 of the experiment [Figure 3]d.

Results revealed difference in BWP especially (P < 0.05) in PQ-treated group when latency time to traverse the beam were compared between week 1 and week 2 of the experiment [Figure 4]a.
Figure 4: (a) Comparison of beam walking performance (Week 1and Week 2) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = 0.16 was the significant difference when week 1 (WK1) was compared with week 2 (WK2). CTL = Control (2 ml/kg distilled water); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1,000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (b) Comparison of beam walking performance (Week 2 and Week 3) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = 0.018, bp = 0.006 were the significant difference when week 2 (WK2) was compared with week 3 (WK3). CTL = Control (2 ml/kg distilled water); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (c) Comparison of beam walking performance (Week 3 and Week 4) in Wistar rats. N = 5; mean ± SEM, Paired t-test; ap = 0.010 was the significant difference when week 3 (WK3) was compared with week 4 (WK4). CTL = Control (2 ml/kg distilled water); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1,000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera

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Results revealed significant (P < 0.05) improvement in BWP in the PQ-treated and PQ + AFPD (1000 mg/kg)-treated groups when latency time to traverse the beam were compared between week 2 and week 3 of the experiment [Figure 4]b.

Results revealed significant (P < 0.05) improvement in BWP in the PQ + AFPD (1,000 mg/kg)-treated group when latency time to traverse the beam was compared between week 3 and week 4 of the experiment [Figure 4]c.

Biochemical studies

Results for the estimation of lipid peroxidation (MDA level) showed a significant (P < 0.05) increase in MDA levels in PQ-treated group, but a decrease (P < 0.05) in PQ + L-dopa-and PQ + AFPD (1000 mg/kg)-treated groups when compared to the control group. Besides, a significant decrease in MDA levels was observed in PQ + L-dopa-and PQ + AFPD (500 mg/kg and 1000 mg/kg)-treated groups when compared to the PQ-treated group [Figure 5]a.
Figure 5: (a) Effect of P. dactylifera on Malondialdehyde levels exposed to Paraquat. N = 5; mean ± SEM; One way analysis of variance, LSD post hoc test; * = P < 0.05 when compared with control. A = p<0.05 when compared to Paraquat. CTL = Control (distilled water 2ml/kg); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1,000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (b) Effect of P. dactylifera on SOD activity following PQ treatment. N = 5; mean ± SEM; One way analysis of variance, LSD post hoc test; * = P < 0.05 when compared with control. A = P < 0.05 when compared to PQ. CTL = Control (distilled water 2ml/kg); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera. (c) Effect of P. dactylifera on GSH activity following PQ treatment. N = 5; mean ± SEM; One way ANOVA, LSD post hoc test; *= P < 0.05 when compared with control. A = P < 0.05 when compared to PQ. CTL = Control (distilled water 2ml/kg); PQ = Paraquat (11.35 mg/kg); L-dopa = L- dopa (10 mg/kg); PDLo = AFPD (500 mg/kg); PDHi = AFPD (1000 mg/kg); AFPD = Aqueous fruit extract of Phoenix dactylifera

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The SOD activity showed a significant decrease in PQ-treated group when compared to control group. However, an increase (P < 0.05) in SOD activity was observed in PQ + L-dopa-treated and PQ + AFPD-treated (1000 mg/kg) groups when compared to the PQ-treated group [Figure 5]b.

GSH activity showed differences (P < 0.05) in all the groups when compared to the control group. Moreover, significant increase in GSH activity was observed in PQ + L-dopa-and PQ + AFPD (500 mg/kg and 1000 mg/kg)-treated groups when compared to the PQ-treated group [Figure 5]c.

Histological studies

Histological examination of cortical cerebral region (LV) and the SN of rats revealed:

In the control, cortical cerebral region presented with normal histoarchitectural features with characteristic six layers of the CC. In particular, layer V revealed pyramidal neuron with normal cytoarchitectural features, well preserved cytoplasm, prominent nuclei and moderately dispersed neuroglia cells [Figure 2]. Relative to the control, section of the PQ-treated group showed neurodegenerative changes as cytoarchitectural distortion: pyknotic nucleus/necrosis, chromatolysis, perineuronal vacuolation and satelliotosis. The L-dopa and AFPD (500 mg/kg)-treated groups revealed mild distortion of the cytoarchitecture as perineuronal vacuolation and satelliotosis. AFPD (1000 mg/kg) showed relatively normal cytoarchitecture when compared to the control [Figure 6].
Figure 6: Micrograph of cerebral cortex (layer V) of Wistar rats (H and E ×250). (a) = Control (distilled water 2 ml/kg) group with normal histoarchitecture. B: Blood Vessel; P: Pyramidal cell; N: Neuropil. (b) = Paraquat (11.35 mg/kg) treated group with histoarchitectural distortions. Pk: Pyknotic nucleus/necrosis; C: Chromatolysis. (c) = Paraquat (11.35 mg/kg) and L- dopa (10 mg/kg) treated group with mild histoarchitectural distortions. V: Perineuronal vacuolation. (d) = Paraquat (11.35 mg/kg) and AFPD (500 mg/kg) treated group with relatively normal histoarchitecture. (e) = Paraquat (11.35 mg/kg) and AFPD (1000 mg/kg) group with relatively normal histoarchitecture. B: Blood Vessel

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SN region of the control showed normal histoarchitecture with variety of cells types and neurons with normal cytoarchitectural features [Figure 2]. Relative to the control, section of the PQ-treated group showed neurodegenerative changes as cytoarchitectural distortion: pyknotic nucleus/necrosis, and perineuronal vacuolation. The L-dopa and AFPD (500 mg/kg)-treated groups revealed mild distortion of the cytoarchitecture as karyorrhexis. AFPD (1000 mg/kg) showed relatively normal cytoarchitecture when compared to the control [Figure 7].
Figure 7: Micrograph of substantia nigra of Wistar rats (H and E, ×250). (a) Control (distilled water 2ml/kg) group with normal histoarchitecture. N: Neuron; Np: Neuropil. (b) Paraquat (11.35 mg/kg) treated group with histoarchitectural distortions. N: Pyknotic nucleus/necrosis/perineuronal vacuolation. (c) Paraquat (11.35 mg/kg) and L- dopa (10 mg/kg) treated group with mild histoarchitectural distortions. N: karyorrhexis. (d) Paraquat (11.35 mg/kg) and AFPD (500 mg/kg) treated group with mild histoarchitectural distortions. N: karyorrhexis. (e) Paraquat (11.35 mg/kg) and AFPD (1000 mg/kg) group with relatively normal histoarchitecture

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  Discussion Top


In this study, the neuroprotective property of aqueous fruit extract of P. dactylifera on cortico-nigral structures of Wistar rats exposed to PQ neurotoxicity was studied using neurobehavioral, biochemical and histological assessments.

BWP is an established tool for the measurement of motor coordination and balance, and is useful to detect motor deficits associated with neurologic conditions including aging, central nervous system (CNS) lesions, genetic and pharmacologic manipulation in rodents.[37] In this study, BWP was assessed for deficit or improved motor coordination and balance functionality. Comparison of BWP across the study period revealed no motor coordination deficit with PQ treatment. This finding is at variance with reports on PQ-induced motor deficit. Following PQ exposure, Mollace et al.,[38] Thiruchelvam et al.[39] and Fahim et al.[40] reported significant difficulties and reduced motor activities, and modified motor coordination which attributed these adverse observations to PQ neurotoxicity. Variance in findings with other reports could be attributed to differences in PQ dosage administered, duration and routes of administration and possibly the age (young adults) of the animal model adopted in this study. Besides, Tinakoua et al.[41] reported slight motor deficits after several weeks of PQ administration in rats which could be similar to the findings of this study.

However, L-dopa and AFPD-treated groups, especially AFPD (1000 mg/kg) showed improvement in motor coordination across the period of study. This is suggestive of potential ameliorative properties of these treatments against PQ-induced motor deficit. Antioxidant agents have been reported to improve motor coordination functions in PQ-induced motor deficit in rodents.[42],[43] An established mechanism of action of L-dopa is the downregulation of reactive oxygen species (ROS) in biological system.[44] P. dactylifera contains beneficial compounds with strong antioxidant activities such as polyphenolics.[24],[45]

MDA is an important biomarker of cellular lipid peroxidation process strongly associated with oxidative stress levels and, the levels of endogenous enzymatic antioxidants including SOD and GSH are critical in the biochemical process of detoxifying ROS production in a pathological state.[42] In this study, remarkable elevation of MDA levels and decline in SOD and GSH activity is suggestive of PQ-triggered oxidative stress. Findings are in line with Mollace et al.,[38] Tinakoua et al.[31] and Ateş et al.[42] who reported significant elevation of MDA levels following PQ administration in animal models.

In this study, observed remarkable decline in lipid peroxidation levels and elevation of endogenous enzymatic antioxidant with L-dopa and AFPD treated groups is indicative of ameliorative activities of the treatments against PQ-triggered oxidative stress conditions. Olanow[44] reported L-dopa protection against ROS-induced neuronal toxicity by eliciting upregulation of endogenous antioxidant molecules such as GSH. In this study AFPD treatment relative to the control, normalized and modulated endogenous antioxidant enzymatic activities which are suggestive of antioxidant activity against PQ generated oxidative stress. Extracts of P. dactylifera has been reported to ameliorate oxidative stress in in vivo and in vitro models by downregulation of MDA levels and upregulation of endogenous antioxidant enzymes.[24],[46] Pheonix dactylifera fruits contain phytonutrients that are high in antioxidants and scavenge free radicals, which is beneficial in relieving oxidative stress associated with several neurological diseases conditions including neurodegeneration and movement disorders.[24],[47]

Neuropathological changes are associated with neurodegeneration triggered by neurotoxins in different regions of the brain.[48] Neurodegenerative changes observed as cytoarchitectural distortions including pyknotic nuclei and necrosis, central chromatolysis, perineuronal vacuolation, and satelliotosis in the brain regions of focus (CC-layer V and SN) following PQ exposure is suggestive of PQ-triggered neurotoxicity. Findings agree with reported toxic properties of PQ on the brain. CNS is vulnerable to PQ-related toxicity which results in cytoarchitectural distortions, neuronal damage, cell death, and glial cells reactivity in different regions of the brain.[12],[49]

Fahim et al.[40] reported remarkably decreased number of dopaminergic neurons in SN exposed to PQ and attributed the loss of neurons to PQ-triggered oxidative stress. PQ exposure triggers mitochondrial dysfunction and glial reactivity, which results in the generation of ROS and neurodegenerative changes.[13] Neuronal damage has been associated with neurological disease conditions including PD with motor impairments as a major clinical hallmark.[50],[51]

Observed mild distortion-to-relatively normal neuronal cytoarchitecture relative to the control with L-dopa and AFPD treated groups is suggestive of ameliorative properties of the treatments against PQ triggered neurodegenerative changes. This finding is in agreement with reports related to therapeutic properties of L-dopa as a established drug in the treatment and management of oxidative stress-associated neurodegenerative disease conditions like PD.[52],[54] Olanow[44] reported L-dopa neuroprotective activity against oxidative stress triggered neurotoxicity. Additionally, findings agreed with the reported neuroprotective properties of P. dactylifera following neuronal pathological changes related to oxidative stress generated as a result of exposure to environmental toxins. Several studies have demonstrated extracts of P. dactylifera fruit to possess neuroprotective activities against neuronal cytoarchitectural changes triggered by exposure to environmental neurotoxins in different regions of the brain.[54],[55],[56]

P. dactylifera contains a variety of phytonutrients such as carotenoids, sterols, tannins, and polyphenols including flavonoids.[57],[58] Abundant in dates are phenolic compounds reported to have strong antioxidant and free radical scavenging activities. These activities have been associated with neuroprotective properties of P. dactylifera.[45],[59],[60],[61],[62] Thus, AFPD, especially at dose 1000 mg/kg, possesses neuroprotective properties comparable to the reference drug, L-dopa.


  Conclusion Top


In conclusion, aqueous fruit pulp extract of P. dactylifera possesses potential neuroprotective properties against PQ-triggered pathological changes in cortico-nigral structures of Wistar rats. Neuroprotective properties could be attributed to bioactive compounds present in AFPD with potent antioxidant activities against ROS-associated PQ-triggered pathologies. Further investigation is recommended to ascertain the efficacy and potentiality of AFPD and other solvent extract forms as a medicament for oxidative stress-associated biochemical and physiological alterations and neuropathologies to enable formulation for therapy.

Patient informed consent

There is no need for patient informed consent.

Ethics committee approval

Ethical clearance for this study was provided by the Ethics Committee on Animal Use and Care, Ahmadu Bello University (ABU), Zaria: ABUCAUC/2018/097.

Financial support and sponsorship

No funding was received.

Conflicts of interest

There are no conflicts of interest to declare.

Author contribution subject and rate

  • Hope Dike Edobor (30%): Design the research, data collection and analyses.
  • Sunday Abraham Musa (20%): Organized the research and supervised the article write up.
  • Uduak Emmanuel Umana (20%): Contributed with comments on research design and slides interpretation.
  • Gbenga Peter Oderinde (15%): Contributed with comments on manuscript organization and write up.
  • Abel Nosereme Agbon (15%): organized the research and supervised the article write-up




 
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