DOSE-DEPENDENT CHRONIC TOXICITY SCREENING OF HINOKITIOL IN ZEBRAFISHES: BEHAVIORAL AND HISTOLOGICAL APPROACH
DOI:
https://doi.org/10.22159/ajpcr.2020.v13i1.34892Keywords:
Zebrafishes, Hinokitiol, Motor impairment, Anxiety, Vital organ toxicityAbstract
Objectives: Parkinson’s disease (PD) is categorized as a movement disorder symptomized by weakening the motor skills of the patients. The root cause of the disease is the neurodegenerative dopaminergic loss in the substantia nigra of the patient’s brain. This havoc disease majorly affects the people above the age of 60 years. Moreover, PD incidences strike almost 70% of the neurological disorders of the aged population worldwide. There are no perfect curative drugs in the medical world for the disease. Since the past few decades, several plant secondary compounds were in preclinical trials to treat this disease. Hinokitiol (HIN), a monoterpenoid from the heartwood of cupressaceous plants, is widely used in hair tonics, toothpaste, cosmetics, and food as an antimicrobial agent. It is well reported as an anti-stroke agent as well.
Methods: In the present study, the dose-dependent (5, 10, 15, 20, and 25 mg/kg) chronic toxicity of HIN was studied for 28 days using zebrafishes. The toxicity was analyzed in vital organs such as brain, liver, kidney, spleen, heart, and blood count followed by behavioral toxicity to target the drug against parkinsonism.
Results: The study revealed that the higher doses of 20 and 25 mg/kg HIN treatment were toxic to the fish brain, spleen, as well as cardiomyocytes. It showed a variation in blood count as well at 10 mg/kg dose itself.
Conclusion: Hence, the study revealed the protective efficacy of the HIN at its therapeutic dosage of 5 mg/kg as a neuroprotective drug, with minimal vital organ toxicities.
Downloads
References
Gourie-Devi M. Epidemiology of neurological disorders in India: Review of background, prevalence and incidence of epilepsy, stroke, Parkinson’s disease and tremors. Neurol India 2014;62:588-98.
Varier KM, Thangarajan S, Chinnasamy A. Effect of imperatorin in neuropathology of Parkinson’s disease: An in silico study. Int J Pharm Clin Res 2017;9:599-609.
Li LH, Wu P, Lee JY, Li PR, Hsieh WY, Ho CC, et al. Hinokitiol induces DNA damage and autophagy followed by cell cycle arrest and senescence in gefitinib-resistant lung adenocarcinoma cells. PLoS One 2014;9:e104203.
Jayakumar T, Hsu WH, Yen TL, Luo JY, Kuo YC, Fong TH, et al. Hinokitiol, a natural tropolone derivative, offers neuroprotection from thromboembolic stroke in vivo. Evid Based Complement Alternat Med 2013;2013:840487.
Westerfield M. The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Brachydanio rerio). Eugene, OR: University of Oregon Press; 1995.
Hill AJ, Howard CV, Cossins AR. Efficient embedding technique for preparing small specimens for stereological volume estimation: zebrafish larvae. J Microsc 2002;206:179-81.
Blechinger SR, Warren JT Jr., Kuwada JY, Krone PH. Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line. Environ Health Perspect 2002;110:1041-6.
Hill A, Howard CV, Strahle U, Cossins A. Neurodevelopmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations. Toxicol Sci 2003;76:392-9.
Tierney KB. Behavioural assessments of neurotoxic effects and neurodegeneration in zebrafish. Biochim Biophys Acta 2011;1812:381-9.
Ramachandran S, Thangarajan S. A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitroproponic acid induced Huntington’s disease-like symptoms in Wistar rats. Chem Biol Interact 2016;256:25-36.
Agrawal SS, Paridhavi M. Herbal Drug Technology. India: Universities Press; 2007. p. 607-14.
Klaassen CS. Principle of toxicology and treatment of poisoning. In: Parker BK, Blumenthal D, Buxton L, editors. Goodman and Gilman’s; Manual of Pharmacology and Therapeutics. New York: McGraw Hill; 2008. p. 1115-9.
Jayshree N, Aparna S, Deepti A, Cynthia PP, Karthick S, Raja N. Proteinaceous compounds from Fragaria ananassa fruit attenuates paraquat induced Parkinson like locomotor and mitochondrial alterations in zebrafish. Int J Pharm Pharm Sci 2015;7:246-51.
Hill AJ, Teraoka H, Heideman W, Peterson RE. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci 2005;86:6-19.
Griffiths BB, Schoonheim PJ, Ziv L, Voelker L, Baier H, Gahtan E. A zebrafish model of glucocorticoid resistance shows serotonergic modulation of the stress response. Front Behav Neurosci 2012;6:68.
Chen YC, Priyadarshini M, Panula P. Complementary developmental expression of the two tyrosine hydroxylase transcripts in zebrafish. Histochem Cell Biol 2009;132:375-81.
Krishnapriya MV, Sumathi T, Arulvasu C, Gopalsamy B, Renjith P. Comparative analysis of potentiality of esculin and hinokitiol (Β-thujaplicin) as anti-parkinsonism drugs: A pilot in silico study. Int J Pharm Pharm Sci 2017;9:108-15.
Anitha P, Bhargavi J, Sravani G, Aruna B, Ramkanth S. Recent progress of dendrimers in drug delivery for cancer therapy. Int J Appl Pharm 2018;10:34-42.
Shamima NA, Biswajit D, Jashabir C. Prospective and retrospective animal model used in the pharmacological screening of anti-cancer drug. Int J Appl Pharm 2018;10:13-8.
Doris K, Kwabena O. Dosage forms of herbal medicinal products and their stability considerations-an overview. J Crit Rev 2017;4:1-8.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.