Buchholzia coriacea seed extract attenuates mercury-induced cerebral and cerebellar oxidative neurotoxicity via NO signaling and suppression of oxidative stress, adenosine deaminase and acetylcholinesterase activities in rats

Document Type : Original Research Article

Authors

1 Department of Biochemistry, Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria

2 Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Alex-Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria

Abstract

Objective: Mercury (Hg) is a classic cumulative neurotoxicant implicated in neuronal deficit via oxidative damage and inflammatory responses. We sought to investigate whether Buccholzia coriacea seed methanol extract (BCSE) would modulate oxidative neurotoxicity induced by Hg in rats.
Materials and Methods: Rats were orally treated with BCSE (200 or 400 mg/kg body weight of rat) for 28 days, while Hg was administered from day 15 to day 28. After sacrifice, antioxidant enzyme activities, reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), and acetylcholinesterase (AchE) and adenine deaminase (ADA) activities were evaluated in the cerebrum and cerebellum of rats.
Results: Mercury induced significant depressions in catalase (CAT) and glutathione peroxidase (GPx) activities and GSH levels, whereas levels of NO and activities of AchE and ADA markedly increased. The histopathology of the brain tissues confirmed these changes. In contrast, BCSE administration prominently modulated the brain NO production and reversed the Hg-induced biochemical alterations comparable to normal control.
Conclusion: Methanol extract of B. coriacea seeds protects the cerebrum and cerebellum against Hg-induced brain damage via its antioxidant and NO modulatory actions.    

Keywords


Abdel-Salam OM, Youness ER, Mohammed
NA, Yassen NN, Khadrawy YA, El-Toukhy
SE, Sleem AA. 2016. Novel neuroprotective
and hepatoprotective effects of citric acid in
acute malathion intoxication. Asian Pac J
Trop Med, 9: 1181-1194.
Adedara IA, Fasina OB, Ayeni MF, Ajayi OM,
Farombi EO. 2019. Protocatechuic acid
ameliorates neurobehavioral deficits via
suppression of oxidative damage,
B. coriacea prevents mercury toxicity
AJP, Vol. 12, No. 1, Jan-Feb 2022 51
inflammation, caspase-3 and
acetylcholinesterase activities in diabetic
rats. Food Chem Toxicol, 125: 170-181.
Adisa RA, Choudhary MI, Olorunsogo OO.
2011. Hypoglycemic activity of Buchholzia
coriacea (Capparaceae) seeds in
streptozotocin-induced diabetic rats and
mice. Exp Toxicol Pathol, 63: 619-625.
Olaiya CO, Omolekan TO. 2013.
Antihypercholesterolemic activity of
ethanolic extract of Buchholzia coriacea in
rats. Afr Health Sci, 13: 1084-1090.
Aebi H. 1983. Catalase. In H. U. Bergmeyer
(Eds.), Methods in enzymatic analysis, pp.
276–286). New York, NY: Academic Press.
Ajaiyeoba EO, Onocha PA, Olanrewaju OT.
2001. In vitro anti-helminthic properties of
Buchholzia coriacea and Gynandropsis
gynandra. Pharm Biol, 39: 217-220.
Akinyemi AJ, Oboh G, Ademiluyi AO. 2015.
Local salt substitutes “Obu-otoyo” activate
acetylcholinesterase and
butyrylcholinesterase and induce lipid
peroxidation in rat brain. Interdis Toxicol, 8:
139-145.
Ansar S. 2015. Pretreatment with
diallylsulphide modulates mercury-induced
neurotoxicity in male rats. Acta Biochim
Pol, 62: 599-603.
Aoyama K, Nakaki T. 2013. Impaired
glutathione synthesis in neurodegeneration.
Int J Mol Sci, 14: 21021-21044.
Bainy AD, de Medeiros MDH, Di Mascio P, de
Almeida EA. 2006. In vivo effects of metals
on the acetylcholinesterase activity of the
Perna perna mussel’s digestive gland.
Biotemas, 19: 35-39.
Bakulski KM, Lee H, Feinberg JI, Wells EM,
Brown S, Herbstman JB, Witter FR, Halden
RU, Caldwell K, Mortensen ME, Jaffe AE,
Moye J, Caulfield LE, Pan Y, Goldman LR,
Feinberg AP, Fallin MD. 2015. Prenatal
mercury concentration is associated with
changes in DNA methylation at TCEANC2
in newborns. Int J Epidemiol, l44: 1249-
1262.
Belaïd-Nouira Y, Bakhta H, Bouaziz M, FlehiSlim I, Haouas Z, Cheikh HB. 2012. Study
of lipid profile and parieto-temporal lipid
peroxidation in AlCl3 mediated
neurotoxicity: Modulatory effect of
fenugreek seeds. Lipids Health Dis, 11: 16-
23.
Cardenas A, Rifas-Shiman SL, Godderis L,
Duca R, Navas-Acien A, Litonjua AA,
DeMeo DL, Brennan KJ, Amarasiriwardena
CJ, Hivert M-F, Gillman MW, Oken E,
Baccarelli AA. 2017. Prenatal exposure to
mercury: associations with global DNA
methylation and hydroxymethylation in
cord blood and in childhood. Environ Health
Perspec, 125: 087022.
Castoldi AF, Coccini T, Manzo L. 2003.
Neurotoxic and molecular effects of
methylmercury in humans. Rev Environ
Health, 18: 19-32.
Cho YM. 2017. Fish consumption, mercury
exposure, and the risk of cholesterol
profiles: findings from the Korea National
Health and Nutrition Examination Survey
2010-2011. Environ Health Toxicol, 32:
e2017014.
Ellman GL, Courtney KD, Andres VJ, Feather‐
Stone RM. 1961. A new and rapid
colorimetric determination of
acetylcholinesterase activity. Biochem
Pharmacol, 7: 88-95.
Eze JI, Ekelozie CF, Nweze NE. 2017.
Immunomodulatory activity of Buchholzia
coriacea seed methanol extract on
Trypanosoma brucei brucei infected mice.
Pharm Biol, 55: 636-640.
Fadillioglu E, Yilmaz HR, Erdogan H, Sogut S.
2003. The activities of tissue xanthine
oxidase and adenosine deaminase and the
levels of hydroxyproline and nitric oxide in
rat hearts subjected to doxorubic: protective
effect of erdosteine. Toxicol, 191: 153-158.
Famurewa AC, Aja PM, Nwankwo OE, Awoke
JN, Maduagwuna EK, Aloke C. 2019.
Moringa oleifera seed oil or virgin coconut
oil supplementation abrogates cerebral
neurotoxicity induced by antineoplastic
agent methotrexate by suppression of
oxidative stress and neuroinflammation in
rats. J Food Biochem, 43: e12748.
Famurewa AC, Ufebe OG, Egedigwe CA,
Nwankwo OE, Obaje GS. 2017. Virgin
coconut oil supplementation attenuates
acute chemotherapy hepatotoxicity induced
by anticancer drug methotrexate via
inhibition of oxidative stress in rats. Biomed
Pharmacother, 87: 437-442.
Flohe L, Gunzler W. 1984. Assays of
glutathione peroxidase. In: S. P. Colowick &
N. O. Kaplan (Eds.), Methods enzymology,
pp. 114–121. New York, NY: Academic
Press.
Gill TS, Teware H, Pande J. 1991. In vivo and
in vitro eff ects of cadmium on selected
Egba et al.
AJP, Vol. 12, No. 1, Jan-Feb 2022 52
enzymes in diff erent organs of the fish
Barbus conchonius Ham. (Rosy barb).
Comp Biochem Physiol Part C, 100: 501-
505.
Giusti G. 1974. Adenosine deaminase. In:
Bergmeyer, M.V. (Ed.), Methods of
Enzymatic Analysis, 2nd ed. Academic
Press, New York, pp. 1092-1098.
Goudarzi M, Kalantar M, Kalantar H. 2017.
The hepatoprotective effect of gallic acid on
mercuric chloride-induced liver damage in
rats. Jundishapur J Natural Pharm Prod, 12:
e12345.
Hegazy HG, Ali EH, Sabry HA. 2016. The
neuroprotective action of naringenin on
oseltamivir (Tamiflu) treated male rats. J
Basic Appl Zool, 77: 83-90.
Ishola IO, Adamson FM, Adeyemi OO. 2017.
Ameliorative effect of kolaviron, a
biflavonoid complex from Garcinia kola
seeds against scopolamine-induced memory
impairment in rats: role of antioxidant
defense system. Metab Brain Dis, 32: 235-
245.
Jollow DJ, Michell JR, Zampaglione N, Gillete
J. 1974. Bromobenzene‐induced liver
necrosis: Protective role of glutathione and
evidence for 3, 4‐bromobenzene oxide as the
hepatotoxic metabolite. Pharmacol, 11: 151-
169.
Lakshmana MK, Desiraju T, Raju TR. 1993.
Mercuric chloride-induced alterations of
levels of noradrenaline, dopamine, serotonin
and acetylcholine esterase activity in
different regions of rat brain during
postnatal development. Arch Toxicol, 67:
422-427.
Lucena GM, Franco JL, Ribas CM, Azevedo
MS, Meotti FC, Gadotti VM, Dafre AL,
Santos AR, Farina M. 2007. Cipura
paludosa extract prevents methyl mercuryinduced neurotoxicity in mice. Basic Clin
Pharmacol Toxicol, 101: 127-131.
Mahmud HA, Seo H, Kim S, Islam MI, Nam KW, Cho H-D, Song H-Y. 2017.
Thymoquinone (TQ) inhibits the replication
of intracellular Mycobacterium tuberculosis
in macrophages and modulates nitric oxide
production. BMC Complement Altern Med,
17: 279-286.
Mesquita M, Pedroso TF, Oliveira CS, Oliveira
VA, Francisco do Santos R, Bizzi CA,
Pereira ME. 2016. Effects of zinc against
mercury toxicity in female rats 12 and 48
hours after HgCl2 exposure. EXCLI J, 15:
256-267.
Mieiro CL, Pereira ME, Duarte AC, Pacheco
M. 2011. Brain as a critical target of mercury
in environmentally exposed fish
(Dicentrarchus labrax)--bioaccumulation
and oxidative stress profiles. Aquatic
Toxicol, 103: 233-240.
Miyazono Y, Gao F, Horie T. 2004. Oxidative
stress contributes to methotrexate- induced
small intestinal toxicity in rats. Scand J
Gastroenterol, 39: 1119-1127.
Moneim AE. 2015. The neuroprotective effect
of berberine in mercury-induced
neurotoxicity in rats. Metab Brain Dis, 30:
935-942.
Ohkawa H, Ohishi N, Yagi K. 1979. Assay for
lipid peroxides in animal tissues by
thiobarbituric acid reaction. Annals
Biochem, 95: 351-358.
Owoeye O, Gabriel MO. 2016. Protective
effects of aqueous extract of Telfairia
occidentalis on mercury-induced
histological and oxidative changes in the rat
hippocampus and cerebellum. Afr J Biomed
Res, 19: 241-247.
Pandya JD, Dave KR, Katyare SS. 2004. Effect
of long-term aluminum feeding on
lipid/phospholipid profiles of rat brain
myelin. Lipids Health Dis, 3: 13-18.
Rao MV, Purohit AR. 2011. Neuroprotection
by melatonin on mercury induced toxicity in
the rat brain. Pharmacol Pharm, 2: 375-385.
Romani R, Antognelli C, Baldracchini F, De
Santis A, Isani G, Giovannini E. 2003.
Increased acetylcholinesterase activities in
specimens of Sparus auratus exposed to sub
lethal copper concentrations. Chem Biol
Interact, 145: 321-329.
Salman MM, Kotb AM, Haridy MA, Hammad
S. 2016. Hepato- and nephroprotective
effects of bradykinin potentiating factor
from scorpion (Buthus occitanus) venom on
mercuric chloride-treated rats. EXCLI J, 15:
807-816.
Sreejayam N, Rao MN. 1997. Nitric oxide
scavenging activity by curcummoids. J
Pharm Pharmacol, 49: 105-107.
Sutton DJ, Tchounwou PB. 2006. Mercuryinduced externalization of
phosphatidylserine and caspase 3 activation
in human liver carcinoma (HepG2) cells. Int
J Environ Res Public Health, 3: 38-42.
Thiagarajan K, Gamit N, Mandal S, Ayyathan
DM, Chandrasekaran R. 2018. Amelioration
of methylmercury induced neural damage
B. coriacea prevents mercury toxicity
AJP, Vol. 12, No. 1, Jan-Feb 2022 53
by essential oil of Selinum vaginatum
(Edgew) C. B. Clarke. Pak J Pharm Sci, 31:
399-404.
Uzar E, Koyuncuoglu HR, Uz E, Yilmaz AR,
Kutluhan S, Kilbas S, Gultekin F. 2006a.
The activities of antioxidant enzymes and
the level malondialdehyde in cerebellum of
rats subjected to methotrexate: protective
effect of caffeic acid phenetyl ester. Mol
Cell Biochem, 291: 63-68.
Uzar E, Sahin O, Koyuncuoglu HR, Uz E, Bas
O, Kilbas S, Yilmaz HR, Yurekli VA,
Kucuker H, Songur A. 2006b. The activity
of adenosine deaminase and the level of
nitric oxide in spinal cord of methotrexate
administered rats: Protective effect of
caffeic acid phenethyl ester. Toxicol, 218:
125-133.
Vardi N, Parlakpinar H, Ozturk F, Ates B, Gul
M, Cetin A, Erdogan A, Otlu A. 2008.
Potent protective effect of apricot and βcarotene on methotrexate-induced intestinal
oxidative damage in rats. Food Chem
Toxicol, 46: 3015-3022.
Vardi N, Parlakpinar H, Cetin A, Erdogan A,
Ozturk IC. 2010. Protective effect of betacarotene on methotrexate-induced oxidative