Amelioration of Lead-Induced Neurotoxicity by Cucurbita pepo (Pumpkin) Fruit Extract in Wister Rats


Authors

  • Bawa Y. Muhammad Department of Biochemistry and Molecular Biology, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi, Nigeria
  • Sulaiman A. Barau ORCiD Department of Biochemistry and Molecular Biology, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi, Nigeria
  • Moses Z. Zaruwa Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Jos 930105, Nigeria
  • Yahaya Abubakar Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Jos 930105, Nigeria
  • Mustapha Salihu Department of Biochemistry and Molecular Biology, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi, Nigeria

DOI:

https://doi.org/10.3923/pjn.2023.11.18

Keywords:

Lead toxicity, molecular docking, nephrotoxicity, neurotoxicity, pumpkin fruit

Abstract

Background and Objective: Lead toxicity is one of the most significant heavy metal toxicities ravaging biotic life especially human and animals. This study aimed to investigate the ameliorative potential of Cucurbita pepo fruit against lead acetate-induced neurotoxicity in rats. Materials and Methods: Rats were orally administered lead acetate (100 mg kg–1 body weight) with or without the fruit extract (200 mg kg–1 body weight) or resveratrol (3.57mg kg–1 body weight) co-administration for 2 weeks. The activity of brain acetylcholinesterase (AchE) was significantly increased among lead acetate-induced animals but decreased significantly in animals administered with pumpkin extract and resveratrol. Similarly, a decreased in glutathione level (GSH) and increased level of hippocampal nitric oxide (NO) was observed in group 2. This was reversed in groups 3 and 4 administered pumpkin fruit extract and resveratrol respectively. Results: Molecular docking studies revealed mild inhibition of AchE and neuronal nitric oxide synthase (nNOS) by 2 compounds of the fruit and resveratrol through weak interaction. Para aminobenzoic and γ-aminobutyric acid have the highest binding affinity to AchE with docking score of -7.1 and -4.1 kcal mol–1, respectively, while γ-aminobutyric acid exhibit higher binding affinity to nNOS than para aminobenzoic acid with docking scores of -3.5 and -2.8 kcal mol–1, respectively. The levels of liver biomarkers increased significantly in group 2 but decreased in group 1, 3 and 4. Similarly, significant increase in urea, creatinine and Na+ with a concomitant reduction in potassium and bicarbonate ions in group 2 compared to other groups were observed. Conclusion: The study revealed that administration of C. pepo fruit extracts has the potential to ameliorate lead acetate-induced neurotoxicity and better liver and kidneys functions.

References

Kumar, A., A. Kumar, M.M.S. Cabral-Pinto, A.K. Chaturvedi and A.A. Shabnam et al., 2020. Lead toxicity: health hazards, influence on food chain, and sustainable remediation approaches. Int. J. Environ. Res. Public Health, Vol. 17.

Muhammad, B.Y., N.Z. Shaban, F.H. Elrashidy and D.A. Ghareeb, 2020. Antioxidant, anti-inflammatory, antiproliferative and antimicrobial activities of combretum glutinosum and gardenia aqualla extracts in vitro. Free Radicals Antioxid., 9: 66-72.

Debnath, B., W.S. Singh and K. Manna, 2019. Sources and toxicological effects of lead on human health. Indian J Med. Spec., 10: 66-71.

IHME., 2019. GBD Compare. Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA. https://vizhub.healthdata.org/gbd-compare.

Rogan, W.J., K.N. Dietrich, J.H. Ware, D.W. Dockery and M. Salganik et al., 2001. The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead. New Engl. J. Med., 344: 1421-1426.

Dalda-Åžekerci, A., K. Karaman and H. YetiÅŸir, 2020. Characterization of ornamental pumpkin (Cucurbita pepo L. var. ovifera (L.) alef.) genotypes: molecular, morphological and nutritional properties. Genet. Resour. Crop Evol., 67: 533-547.

Chawla, R., 2014. Practical Clinical Biochemistry: Methods and Interpretations. 4th Edn., Jaypee Brothers Medical Publ., India, ISBN-13: 978-9350909423, Pages: 345.

Green, L.C., D.A. Wagner, J. Glogowski, P.L. Skipper, J.S. Wishnok and S.R. Tannenbaum, 1982. Analysis of nitrate, nitrite and [15N]nitrate in biological fluids. Anal. Biochem., 126: 131-138.

Hiroaki, O., S. Kazuyo, N. Nobuyuki and N. Akio, 1977. New enzymatic assay of cholinesterase activity. Clinica Chim. Acta, 80: 87-94.

Jollow, D.J., J.R. Mitchell, N. Zampaglione and J.R. Gillette, 1974. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 11: 151-169.

Badr, S.E.A., M. Shaaban, Y.M. Elkholy, M.H. Helal, A.S. Hamza, M.S. Masoud and M.M.E. Safty, 2011. Chemical composition and biological activity of ripe pumpkin fruits (Cucurbita pepoL.) cultivated in Egyptian habitats. Nat. Prod. Res., 25: 1524-1539.

Berroukche, A., M. Terras, S. Hebri and A. Amara, 2019. GC-SM analysis composition and antibacterial activity of Cucurbita pepo (Pumpkin) seeds harvested in Western Algeria. Proceeding of 5th International Meeting on Traditional & Alternative Medicine, February, 23 and 24. 2019, J. Regener. Med., 38-38.

Pettersen, E.F., T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng and T.E. Ferrin, 2004. UCSF chimera-A visualization system for exploratory research and analysis. J. Comput. Chem., 25: 1605-1612.

Tai, W., L. He, X. Zhang, J. Pu and D. Voronin et al., 2020. Characterization of the receptor-binding domain (rbd) of 2019 novel coronavirus: implication for development of rbd protein as a viral attachment inhibitor and vaccine. Cell. & Mol. Immunol., 17: 613-620.

Johnson, T.O., A.O. Abolaji, S. Omale, I.Y. Longdet and R.J. Kutshik et al., 2021. Benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced locomotor and reproductive senescence and altered biochemical parameters of oxidative damage in Canton-S Drosophila melanogaster. Toxicol. Rep., 8: 571-580.

Trang, A. and P.B. Khandhar, 2020. Physiology, Acetylcholinesterase. In: StatPearls, Aboubakr, S., A. Abu-Ghosh, A.B. Acharya, P.A. Sedeh and T.C. Aeby et al, (Eds.). StatPearls Publishing LLC, USA,.

Bellinger, D.C., 2008. Very low lead exposures and children`s neurodevelopment. Curr. Opin. Pediatr., 20: 172-177.

Akhoon, B.A., S. Choudhary, H. Tiwari, A. Kumar and M.R. Barik et al., 2020. Discovery of a new donepezil-like acetylcholinesterase inhibitor for targeting Alzheimer's disease: Computational studies with biological validation. J. Chem. Inform. Model., 60: 4717-4729.

McHardy, S.F., H.Y.L. Wang, S.V. McCowen and M.C. Valdez, 2017. Recent advances in acetylcholinesterase inhibitors and reactivators: An update on the patent literature (2012-2015). Expert Opin. Ther. Pat., 27: 455-476.

Sahin, Z., A. Ozkaya, M. Uckun, E. Yologlu and M. Kuzu et al., 2019. Evaluation of the effects of cyclotrichium niveum on brain acetylcholinesterase activity and oxidative stress in male rats orally exposed to lead acetate. Cell. Mol. Biol., 65: 3-8.

Saxena, G., U. Pathak and S.J.S. Flora, 2005. Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats. Toxicology, 214: 39-56.

Picón-Pagès, P., J. Garcia-Buendia and F.J. Muñoz, 2019. Functions and dysfunctions of nitric oxide in brain. Biochim. Biophys. Acta (BBA) Mol. Basis Dis., 1865: 1949-1967.

Abdel Moneim, A.E., 2012. Flaxseed oil as a neuroprotective agent on lead acetate-induced monoamineric alterations and neurotoxicity in rats. Biol. Trace Elem. Res., 148: 363-370.

Abirami, N., V.S. Raju and K. Rajathi, 2007. Effect of Semecarpus anacardium against lead induced toxicity in rats. Anc. Sci. Life, 27: 24-27.

Sharma, A., V. Sharma and L. Kansal, 2010. Amelioration of lead-induced hepatotoxicity by Allium sativum Extracts in Swiss albino mice. Libyan J. Med., Vol. 5.

Downloads

Published

11.01.2023

Issue

Section

Research Article

How to Cite

Muhammad, B. Y., Barau, S. A., Zaruwa, M. Z., Abubakar, Y., & Salihu, M. (2023). Amelioration of Lead-Induced Neurotoxicity by Cucurbita pepo (Pumpkin) Fruit Extract in Wister Rats. Pakistan Journal of Nutrition, 22, 11–18. https://doi.org/10.3923/pjn.2023.11.18