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Disorders of Hippocampus Facilitated by Hypertension in Purine Metabolism Deficiency is Repressed by Naringin, a Bi-flavonoid in a Rat Model via NOS/cAMP/PKA and DARPP-32, BDNF/TrkB Pathways

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Abstract

Individuals who are hypertensive have a higher tendency of predisposition to other genetic diseases including purine metabolism deficiency. Therefore, the search for nontoxic and effective chemo protective agents to abrogate hypertension-mediated genetic disease is vital. This study therefore investigated the repressive effect of naringin (NAR) against disorder of hippocampus facilitated by hypertension in purine metabolism deficiency. Male albino rats randomly assigned into nine groups (n = 7) were treated for 35 days. Group I: control animals, Group II was treated with 100 mg/kg KBrO3, Group III was treated with 250 mg/kg caffeine, and Group IV was treated with 100 mg/kg KBrO3 + 250 mg/kg caffeine. Group V was administered with 100 mg/kg KBrO3 + 100 mg/kg haloperidol. Group VI was administered with 100 mg/kg KBrO3 + 50 mg/kg NAR. Group VII was administered with 250 mg/kg caffeine + 50 mg/kg NAR, and Group VIII was administered with 100 mg/kg KBrO3 + 250 mg/kg caffeine + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The sub-acute exposure to KBrO3 and CAF induced hypertension and mediated impairment in the hippocampus cells. This was apparent by the increase in PDE-51, arginase, and enzymes of ATP hydrolysis (ATPase and AMPase) with a simultaneous increase in cholinergic (AChE and BuChE) and adenosinergic (ADA) enzymes. The hypertensive-mediated hippocampal impairment was associated to alteration of NO and AC signaling coupled with lower expression of brain-derived neurotrophic factor and its receptor (BDNF-TrkB), down regulation of Bcl11b and DARPP-32 which are neurodevelopmental proteins, and hypoxanthine accumulation. However, these features of CAF-mediated hippocampal damage in KBrO3-induced hypertensive rats were repressed by post-treatment with NAR via production of neuro-inflammatory mediators, attenuation of biochemical alterations, stabilizing neurotransmitter enzymes, regulating NOS/cAMP/PKA and DARPP-32, BDNF/TrkB signaling, and restoring hippocampal tissues.

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Abbreviations

ACh:

Acetylcholine

AChE:

Acetylcholinesterase

ADA:

Adenosine deaminase

AMP:

Adenosine monophosphate

ATP:

Adenosine triphosphate

BCl11b:

B cell leukemia 11B

BDNF:

Brain-derived neurotrophic factor

BuCh:

Butyrylcholine

BuChE:

Butyrylcholinesterase

CAF:

Caffeine

CaMKII:

Calcium/calmodulin-regulated protein kinases

cDNA:

Cyclic deoxyribonucleic acid

cGMP:

Cyclic guanosine monophosphate

DBP:

Diastolic blood pressure

DNA:

Deoxyribonucleic acid

DMAB:

Dimethyl amino benzaldehyde

DTNB:

5,5-Dithio-bis 2-benzoic acid

DARPP-32:

Dopamine- and cAMP-regulated phosphoprotein-32

GC:

Guanylate cyclase

GMP:

Guanosine monophosphate

HAL:

Haloperidol

HLNS:

Hepatic Lesch-Nyhan syndrome

hMDA:

Hippocampus malondialdehyde

HGPRT:

Hypoxanthine guanine phosphoribosyl transferase

IMP:

Inosine monophosphate

KBrO3 :

Potassium bromate

LNS:

Lesch-Nyhan syndrome

NAR:

Naringin

NO:

Nitric oxide

MDA:

Malondialdehyde

MAO-A:

Monoamine oxidase-A

MRNA:

Messenger ribonucleic acid

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PDE-5:

Phosphodiesterase-5

PCR:

Polymerase chain reaction

PUFAs:

Poly unsaturated fatty acid

PKA:

Protein kinase A

PKG:

Protein kinase A

PNPP:

P-nitrophenyl phenyl phosphate

ROS:

Reactive oxygen species

RT:

Reverse transcriptase

RNA:

Ribonucleic acid

SEM:

Standard mean error

SBP:

Systolic blood pressure

TBA:

Thiobarbituric acid

TBARS:

Thiobarbituric reactive substance

TCA:

Trichloroacetic acid

TrkB:

Tropomyosin receptor kinase B

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Authors and Affiliations

  1. Applied Biochemistry and Molecular Toxicology Research Group, Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria

    J. K. Akintunde, O. S. Abinu, K. F. Taiwo, R. A. Sodiq, A. D. Folayan & A. D. Ate

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  1. J. K. Akintunde
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  2. O. S. Abinu
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  3. K. F. Taiwo
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Contributions

Akintunde J.K: Conceptualization; methodology; investigation; supervision; software; writing, original draft; writing, review and editing. Abinu O.S: Investigation. Taiwo K.F: Investigation Sodiq R.A: Investigation Folayan A.D: Writing manuscript draft. Ate A.D: Editing.

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Akintunde, J.K., Abinu, O.S., Taiwo, K.F. et al. Disorders of Hippocampus Facilitated by Hypertension in Purine Metabolism Deficiency is Repressed by Naringin, a Bi-flavonoid in a Rat Model via NOS/cAMP/PKA and DARPP-32, BDNF/TrkB Pathways. Neurotox Res 40, 2148–2166 (2022). https://doi.org/10.1007/s12640-022-00578-4

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