Jobelyn® ameliorates anxiety response and oxido-inflammatory markers induced by tramadol use and discontinuation in rats
Taiwo O. Afe, Akinyinka Alabi, Abayomi M. Ajayi, Ayotunde O. Ale, Oluwatoyin A. Fasesan, Olawale O. Ogunsemi
Abstract
Jobelyn® is a multi-functional natural dietary supplement made from Sorghum bicolour with very high anti-oxidant and anti-inflammatory capacities. The study investigated the role of Jobelyn® in the attenuation of oxido-inflammatory markers induced by tramadol use, abuse and discontinuation over 17 days in rats. The experimental observational study was carried out using male adult albino rats weighing between 100 and 170 g. The experimental design involved five groups. Rats were randomly divided into groups of five, consisting of group 1 (normal control rats), and group 2 (rats treated with tramadol at 40 mg/kg/day) were administered for 10 days and discontinued for seven days. Group 3 administered incremental doses of tramadol from 40 mg/kg/day to 100 mg/kg/day over 10 days and discontinued for seven days. A similar treatment protocol was administered for group 4 and group 5 but were treated with Jobelyn® at a dose of 200 mg/kg/day at the discontinuation phases for seven days. Behavioral assessments (elevated plus maze model of anxiety and open field model of locomotor activity) and biomarkers of oxido-inflammatory stress were assessed. Tramadol-treated groups had significant anxiety responses and locomotory deficits in comparison to the control group. Tramadol-treated groups had significant elevations of nitrites and malondehyde and reduced enzymatic markers such as catalase, glutathione, reduced glutathione, superoxide dismutase, G-s-transferase, glutamic acid decarboxylase and increased activity of acetylcholinesterase when compared to control group. Administration of Jobelyn® attenuated the responses and ameliorated the oxido-inflammatory biomarkers similar to levels in control group. Tramadol induces oxido-inflammatory stress markers in the prefrontal, striatum and hippocampus in rats. Anxiety and locomotory behavioral actions on tramadol treatment were elevated despite discontinuation for seven days. Thus, Jobelyn® at 200 mg/kg/day ameliorated oxido-inflammatory markers induced by tramadol and decreased anxiety responses in albino rats.
Keywords
References
- Rostam‐Abadi Y, Gholami J, Amin‐Esmaeili M, Safarcherati A, Mojtabai R, Ghadirzadeh MR, Rahimi H, Rahimi‐Movaghar A (2020) Tramadol use and public health consequences in Iran: a systematic review and meta‐analysis. Addiction. 115 (12): 2213-2242. doi: 10.1111/add.15059
- Subedi M, Bajaj S, Kumar MS, Mayur YC (2019) An overview of tramadol and its usage in pain management and future perspective. Biomedicine and Pharmacotherapy. 111: 443-451. doi: 10.1016/j.biopha.2018.12.085
- Ojha R, Bhatia SC (2010) Tramadol dependence in a patient with no previous substance history. The Primary Care Companion for CNS Disorders. 12 (1): PCC.09100779. doi: 10.4088/PCC.09100779ecr
- Klein A (2019) Drug problem or medicrime? Distribution and use of falsified tramadol medication in Egypt and West Africa. Journal of Illicit Economies and Development. 1 (1): 52-62. doi: 10.31389/jied.10
- Bassiony MM, Salah El-Deen GM, Yousef U, Raya Y, Abdel-Ghani MM, El-Gohari H, Atwa SA (2015) Adolescent tramadol use and abuse in Egypt. The American Journal of Drug and Alcohol Abuse. 41 (3): 206-211. doi: 10.3109/ 00952990.2015.1014959
- Sharma AP, Sharma G, Tyagi S, Devana SK, Mavuduru RS, Bora GS, Singh SK (2021) Safety and efficacy of “on-demand” tramadol in patients with premature ejaculation: an updated meta-analysis. International Brazilian Journal of Urology. 47 (5): 921-934. doi: 10.1590/S1677-5538.IBJU.2020.0561
- Bumpus JA (2020) Low-dose tramadol as an off-label antidepressant: a data mining analysis from the patients’ perspective. ACS Pharmacology and Translational Science. 3 (6): 1293-1303. doi: 10.1021/acsptsci.0c00132
- Salah S, Wagih M, Zaki A, Fathy W, Eid A (2020) Long-term effects of tramadol on the reproductive function of male albino rats: an experimental biochemical and histopathological study. Middle East Fertility Society Journal. 24 (3): 1-6. doi: 10.1186/s43043-019-0003-0
- Nakhaee S, Hoyte C, Dart RC, Askari M, Lamarine RJ, Mehrpour O (2021) A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment. Forensic Toxicology. 39: 293-310. doi: 10.1007/s11419-020-00569-0
- Mahmoud AM, Hassanein EH (2022) Tramadol as an analgesic. The neurosciences of anaesthetics and analgesics: treatments, mechanisms, and adverse reactions of anesthetics and analgesics. 181-191. Academic press. ISBN: ISBN 9780128202371. doi: 10.1016/B978-0-12-820237-1.00018-1
- Mousavi K, Manthari RK, Najibi A, Jia Z, Ommati MM, Heidari R (2021) Mitochondrial dysfunction and oxidative stress are involved in the mechanism of tramadol-induced renal injury. Current Research in Pharmacology and Drug Discovery. 2: 100049. doi: 10.1016/j.crphar.2021.100049
- ORCD/OCDE (2001) OECD guideline for testing of chemicals. Acute oral toxicity-fixed dose procedure. Organization for Economic Co-Operation and Development. Paris, France. 420: 1-14.
- Ali HA, Afifi M, Saber TM, Makki AA, Keshta AT, Baeshen M, Al-Farga A (2020) Neurotoxic, hepatotoxic and nephrotoxic effects of tramadol administration in rats. Journal of Molecular Neuroscience. 70 (12): 1934-1942. doi: 10.1007/s12031-020-01592-x
- Omogbiya AI, Ben-Azu B, Eduviere AT, Eneni AE, Nwokoye PO, Ajayi AM, Umukoro S (2021) Monosodium glutamate induces memory and hepatic dysfunctions in mice: ameliorative role of Jobelyn® through the augmentation of cellular antioxidant defense machineries. Toxicological Research. 37 (3): 323-335. doi: 10.1007/ s43188-020-00068-9
- Aghajanpour F, Boroujeni ME, Jahanian A, Soltani R, Ezi S, Khatmi A, Amini A (2020) Tramadol: a potential neurotoxic agent affecting prefrontal cortices in adult male rats and PC-12 cell line. Neurotoxicity Research. 38 (2): 385-397. doi: 10.1007/s12640-020-00214-z
- Rafati A, Yasini SM, Dashti-Rahmatabadi MH, Pakdel S, Norani F (2006) Tramadol dependence rate as compared with morphine in rats. World Journal of Medical Science. 1 (1): 40-43. Corpus ID:13667675.
- Sherif F, Oreland L (1995) Effect of the GABA-transaminase inhibitor vigabatrin on exploratory behaviour in socially isolated rats. Behavioral Brain Research. 72 (1-2): 135-40. doi: 10.1016/0166-4328(96)00047-2
- Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. The Journal of Biological Chemistry. 247 (10): 3170-3175. PMID: 4623845.
- Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Analytical Biochemistry. 126 (1): 131-138. doi: 10.1016/0003-2697(82) 90118-x
- Jollow DJ, Mitchell JR, Zampaglione NA, Gillette JR (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 11 (3): 151-169. doi: 10.1159/000136485
- Goth L (1991) A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta. 196 (2-3): 143-151. doi: 10.1016/0009-8981(91)90067-m
- Yu K, Hu S, Huang J, Mei LH (2011) A high-throughput colorimetric assay to measure the activity of glutamate decarboxylase. Enzyme and Microbial Technology. 49 (3): 272-276. doi: 10.1016/j.enzmictec.2011.06.007
- Ellman GL, Courtney KD, Andres Jr V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 7 (2): 88-95. doi: 10.1016/0006-2952(61)90145-9
- Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the biuret reaction. The Journal of Biological Chemistry. 177 (2): 751-766. doi: 10.1016/s0021-9258(18)57051-6
- Omorogbe O, Ajayi AM, Ben-Azu B, Oghwere EE, Adebesin A, Aderibigbe AO, Okubena O, Umukoro S (2018) Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice. Biomedical Pharmacotherapy. 98: 585-593. doi: 10.1016/j.biopha.2017.12.098
- Nagababu E, Rifkind JM, Boindala S, Nakka L (2010) Assessment of antioxidant activity of eugenol in vitro and in vivo. Methods Molecular Biology. 610: 165-180. doi: 10.1007/978-1-60327-029-8_10
- George O, Koob GF (2010) Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. Neuroscience and Biobehavioral Review. 35 (2): 232-247. doi: 10.1016/j.neubiorev.2010.05.002
- Omara-Reda H, Ouachikh O, Hamdi D, Lashin M, Hafidi A (2023) Reinforcing effect of tramadol in the rat. Neuroscience Letters. 796: 137053. doi: 10.1016/j.neulet.2023.137053
- Hussein SA, Abdel Aal SA, Isamil HK (2017) Neurodegeneration and oxidative stress induced by tramadol administration in male rats: the effect of its withdrawal. Benha Veterinary Medical Journal. 33 (2): 149-159. doi: 10.21608/BVMJ.2017.30017
- Soltani R, Boroujeni ME, Aghajanpour F, Khatmi A, Ezi S, Mirbehbahani SH, Abdollahifar MA, Akhlaghpasand M, Aliaghaei A, Heidari MH (2020) Tramadol exposure upregulated apoptosis, inflammation and autophagy in PC12 cells and rat’s striatum: An in vitro-in vivo approach. Journal of Chemical Neuroanatomy. 109: 101820. doi: 10.1016/j.jchemneu.2020.101820
- Lobo MK, Nestler EJ (2011) The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons. Frontiers in Neuroanatomy. 5: 41. doi: 10.3389/fnana.2011.00041
- Mandyam CD (2022) The hippocampus and addiction: focus on plasticity and circuitry in the hippocampus. In handbook of substance misuse and addictions: From Biology to Public Health. 1-22. Springer International Publishing. doi: 10.1007/978-3-030-67928-6_24-1
- El-Hadidy MA, Helaly AM (2015) Medical and psychiatric effects of long-term dependence on high dose of tramadol. Substance Use and Misuse. 50 (5): 582-589. doi: 10.3109/10826084.2014.991406
- Ezi S, Boroujeni ME, Khatmi A, Vakili K, Fathi M, Abdollahifar MA, Aghajanpour F, Soltani R, Mirbehbahani SH, Khodagholi F, Aliaghaei A, Farahani RM (2021) Chronic exposure to tramadol induces neurodegeneration in the cerebellum of adult male rats. Neurotoxicity Research. 39 (4): 1134-1147. doi: 10.1007/ s12640-021-00354-w
- Singh A, Kukreti R, Saso L, Kukreti S (2019) Oxidative stress: a key modulator in neurodegenerative diseases. Molecules. 24 (8): 1583. doi: 10.3390/molecules24081583
- Pierini D, Bryan NS (2015) Nitric oxide availability as a marker of oxidative stress. Methods in Molecular Biology. 1208: 63-71. doi: 10.1007/978-1-4939-1441-8_5
- Dib M, Garrel C, Favier A, Robin V, Desnuelle C (2002) Can malondialdehyde be used as a biological marker of progression in neurodegenerative disease?. Journal of Neurology. 249 (4): 367-374. doi: 10.1007/s004150200025
- Rinne JO, Kaasinen V, Järvenpää T, Någren K, Roivainen A, Yu M, Oikonen V, Kurki T (2003) Brain acetyl cholinesterase activity in mild cognitive impairment and early Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry. 74 (1): 113-115. doi: 10.1136/jnnp.74.1.113
- Eskandari Z, Mostafavi H, Hosseini M, Mousavi SE, Ramazani S, Dadashi M (2021) A sham-controlled clinical trial to examine the effect of bilateral tDCS on craving, TNF-α and IL-6 expression levels, and impulsivity of males with opioid use disorder. Journal of addictive diseases. 39 (3): 347-356. doi: 10.1080/10550887.2021.1883208
- ElShebiney S, Elgohary R, El-Shamarka M, Mowaad N, Abulseoud OA (2023) Natural polyphenols-resveratrol, quercetin, magnolol, and β-catechin-block certain aspects of heroin addiction and modulate striatal IL-6 and TNF-α. Toxics. 11 (4): 379. doi: 10.3390/toxics11040379
- Asehinde S, Ajayi A, Bakre A, Omorogbe O, Adebesin A, Umukoro S (2018) Effects of Jobelyn® on isoniazid-induced seizures, biomarkers of oxidative stress and glutamate decarboxylase activity in mice. Basic and Clinical Neuroscience. 9 (6): 389-396. doi: 10.32598/bcn.9.6.389
Submitted date:
01/07/2024
Reviewed date:
02/19/2024
Accepted date:
02/28/2024
Publication date:
02/29/2024