Mitigatory Roles of Asystasia Gangetica On Glutathione and Metabolic Enzyme Activities in The Cerebellum of Flunitrazepam-Induced Neurotoxicity in Wistar Rats

References

[1] Akhigbe RE, Oluwole DT, Adegoke TE, Hamed MA, Anyogu DC, Ajayi AF. Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury. Redox Rep. 2022;27(1):111–118. doi:10.1080/13510002.2022.2074128

[2] Ajayi AF, Oluwole DT, Akhigbe RE, Hamed MA, Ajayi LO. Proton pump dysfunction and upregulation of caspase-3 activity via oxidative-sensitive signaling mediate rohypnol-induced testicular toxicity. Andrologia. 2023;2023:7215328. doi:10.1155/2023/7215328

[3] Eze GI, Akonoafua KA. Effects of oral ingestion of flunitrazepam and alcohol mixture on the cerebellum of the adult Wistar rat. NISEB J. 2019;19(3).

[4] Udodi PS, Ezejindu DN. A study on the neurotoxicity of flunitrazepam (Rohypnol) administration on the cerebral cortex of adult Wistar rats. Adv Pharmacol Pharm. 2021;9(2):26–32. doi:10.13189/app.2021.090202

[5] Ohshima T. A case of drug-facilitated sexual assault by the use of flunitrazepam. J Clin Forensic Med. 2006;13(1):44–45. doi:10.1016/j.jcfm.2005.05.006

[6] Turina AV, Perillo MA, et al. Flunitrazepam–membrane binding. In: Neuropathology of Drug Addictions and Substance Misuse. 2016.

[7] United States Drug Enforcement Administration. Drug Fact Sheet: Rohypnol. October 2022. Available at: https://www.dea.gov/factsheets/rohypnol

[8] Griffin CE, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013;13(2):214–223.

[9] National Center for Biotechnology Information. PubChem Compound Summary for CID 3380, Flunitrazepam [Internet]. 2025. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Flunitrazepam

[10] Aoyama K. Glutathione in the brain. Int J Mol Sci. 2021;22(9):5010. doi:10.3390/ijms22095010

[11] Kumar KA, Umamaheswari M, Sivasanmugam AT, Subhadradevi V, Somanathan SS, Ravi T. Protective effect of Asystasia gangetica on oxidative damage in the small intestine of streptozotocin-induced diabetic rats. Orient Pharm Exp Med. 2009;9(4):307–314.

[12] Uroko RI, Amarachi A, Nweje-Anyalowu PC, Uko OE, Abuachi PT. Effects of Asystasia gangetica extract on biochemical parameters and liver histomorphology of monosodium glutamate-induced rats. Plant Biotechnol Persa. 2021;3(2):1–10.

[13] Dringen R, Hirrlinger J. Glutathione pathways in the brain. Biol Chem. 2003;384(4):505–516. doi:10.1515/BC.2003.059

[14] López-Pedrajas R, Ramírez-Lamelas DT, Muriach B, et al. Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum. Front Cell Neurosci. 2015;9:279. doi:10.3389/fncel.2015.00279

[15] Shukla GS, Srivastava RS, Chandra SV. Glutathione status and cadmium neurotoxicity: studies in discrete brain regions of growing rats. Fundam Appl Toxicol. 1988;11(2):229–235. doi:10.1016/0272-0590(88)90147-9

[16] Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97(6):1634–1658. doi:10.1111/j.1471-4159.2006.03907.x

[17] Pei J, Pan X, Wei G, Hua Y. Research progress of glutathione peroxidase family (GPX) in redoxidation. Front Pharmacol. 2023;14:1147414. doi:10.3389/fphar.2023.1147414

[18] Chen PH, Tjong WY, Yang HC, et al. Glucose-6-phosphate dehydrogenase, redox homeostasis and embryogenesis. Int J Mol Sci. 2022;23(4):2017. doi:10.3390/ijms23042017

[19] Meng Q, Zhang Y, Hao S, et al. Recent findings in the regulation of G6PD and its role in diseases. Front Pharmacol. 2022;13:932154. doi:10.3389/fphar.2022.932154

[20] Dave A, Maru L, Jain A. LDH (lactate dehydrogenase): a biochemical marker for the prediction of adverse outcomes in pre-eclampsia and eclampsia. J Obstet Gynaecol India. 2016;66(1):23–29. doi:10.1007/s13224-014-0645-x

@article{1719355,
      author = {Gabriel Emerson Ebito, Bamidele Ponle Fakunle, Adejinmi Suliat Opeyemi},
      title = {Mitigatory Roles of Asystasia Gangetica On Glutathione and Metabolic Enzyme Activities in The Cerebellum of Flunitrazepam-Induced Neurotoxicity in Wistar Rats},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {9},
      number = {12},
      pages = {3348-3353},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1719355.pdf},
      abstract = {non-pharmaceutical use of drugs negatively impacts individuals, communities, and global public health. Flunitrazepam (FNZ), a benzodiazepine commonly associated with drug abuse and drug-facilitated sexual assault, exerts its effects by acting on GABA-A receptors. The brain is particularly vulnerable to oxidative damage due to its high oxygen consumption, relatively low antioxidant reserves, and abundance of polyunsaturated lipids. This study evaluated the protective effect of Asystasia gangetica aqueous leaf extract (AGLE) against FNZ-induced neurotoxicity in the cerebellum of Wistar rats. Forty adult male Wistar rats (200–230 g) were randomly allocated into four groups (n = 10 per group): Group 1 (control, distilled water), Group 2 (FNZ, 3 mg/kg bw), Group 3 (FNZ 3 mg/kg bw + AGLE 500 mg/kg bw), and Group 4 (AGLE 500 mg/kg bw). All treatments were administered orally for 21 days. Biochemical parameters assayed in cerebellar homogenates included reduced glutathione (GSH), glutathione peroxidase (GPx), oxidized glutathione (GSSG), GSH/GSSG ratio, glucose-6-phosphate dehydrogenase (G6PD), and lactate dehydrogenase (LDH). FNZ administration caused significant reductions in GSH, GPx, and GSH/GSSG ratio, and significant elevations in GSSG and LDH activity, consistent with oxidative stress and neuronal injury. G6PD activity showed a non-significant decrease. Co-administration of AGLE with FNZ substantially reversed these biochemical alterations toward control values. These findings demonstrate that A. gangetica aqueous leaf extract confers protective effects against FNZ-induced cerebellar oxidative neurotoxicity, and warrants further investigation as a potential adjunct therapeutic agent.},
      keywords = {Flunitrazepam, Neurotoxicity, Glutathione, Cerebellum, Asystasia Gangetica},
      month = {June},
      doi = {https://doi.org/10.64388/IREV9I12-1719355}
  }