Examination of the effect of bupivacaine on brain tissue in rats with induced experimental renal failure

Neurotoxicity of bupivacaine in renal failure

Authors

Keywords:

bupivacaine, neurotoxicity, renal failure

Abstract

Background/Aim: Local anesthetics are frequently used and often considered harmless, but they can precipitate local anesthetic systemic toxicity (LAST) when accidentally administered intravascularly or when a toxic dose is rapidly absorbed, which can result in mortality. In cases of renal function impairment, the altered pharmacokinetics of local anesthetics lead to a lowered toxicity threshold. In this study, the aim was to histopathologically investigate the increase in neurotoxicity in the central nervous system due to bupivacaine in experimental renal failure.

Methods: In the study, a total of 28 male Wistar albino rats, aged 8-10 weeks, were evenly divided into four groups: Group C (control group) received intraperitoneal 1 mL/kg saline; Group G (glycerol group) received intramuscular 10 mL/kg glycerol, Group GB (glycerol+bupivacaine group) received intramuscular 10 mL/kg glycerol followed by intraperitoneal 4 mg/kg bupivacaine; and Group B (bupivacaine group) received intraperitoneal 4 mg/kg bupivacaine. All rats were sacrificed after the experimental period. Tissue samples were preserved and stained with hematoxylin-eosin for histopathological analyses. TRPM2 and Reelin levels in brain tissue were measured using immunohistochemical methods.

Results: In the histopathological examination, Group G exhibited higher Reelin and TRPM2 levels compared to all other groups (P<0.001). In Group GB, both Reelin and TRPM2 immunoreactivity were significantly higher compared to Group B (P<0.001).

Conclusion: It can be concluded that renal dysfunction increases neurotoxicity in brain tissue associated with bupivacaine.

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References

Fozzard HA, Lee PJ, Lipkind GM. Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des. 2005;11(21):2671-86. doi: 10.2174/1381612054546833. DOI: https://doi.org/10.2174/1381612054546833

Cherobin ACFP, Tavares GT. Safety of local anesthetics. An Bras Dermatol. 2020;95(1):82-90. doi: 10.1016/j.abd.2019.09.025. DOI: https://doi.org/10.1016/j.abd.2019.09.025

On'Gele MO, Weintraub S, Qi V, Kim J. Local Anesthetics, Local Anesthetic Systemic Toxicity (LAST), and Liposomal Bupivacaine. Clin Sports Med. 2022;41(2):303-315. doi: 10.1016/j.csm.2021.12.001. DOI: https://doi.org/10.1016/j.csm.2021.12.001

Sagir A, Goyal R. An assessment of the awareness of local anesthetic systemic toxicity among multi-specialty postgraduate residents. J Anesth. 2015;29(2):299-302. doi: 10.1007/s00540-014-1904-9. DOI: https://doi.org/10.1007/s00540-014-1904-9

Safety Committee of Japanese Society of Anesthesiologists. Practical guide for the management of systemic toxicity caused by local anesthetics. J Anesth. 2019;33(1):1-8. doi: 10.1007/s00540-018-2542-4. DOI: https://doi.org/10.1007/s00540-018-2542-4

Tsuchiya H, Mizogami M, Ueno T, Shigemi K. Cardiotoxic local anesthetics increasingly interact with biomimetic membranes under ischemia-like acidic conditions. Biol Pharm Bull. 2012;35(6):988-92. doi: 10.1248/bpb.35.988. DOI: https://doi.org/10.1248/bpb.35.988

Singh AP, Junemann A, Muthuraman A, Jaggi AS, Singh N, Grover K, et al. Animal models of acute renal failure. Pharmacol Rep. 2012;64(1):31-44. doi: 10.1016/s1734-1140(12)70728-4. DOI: https://doi.org/10.1016/S1734-1140(12)70728-4

Ahmed RF, Okasha AM, Hafiz SHI, Abdel-Gaber SA, Yousef RKM, Sedik WF. Guanosine protects against glycerol-induced acute kidney injury via up-regulation of the klotho gene. Iran J Basic Med Sci. 2022;25(3):399-404. doi: 10.22038/ijbms.2022.60579.13428.

Takahashi N, Kozai D, Kobayashi R, Ebert M, Mori Y. Roles of TRPM2 in oxidative stress. Cell Calcium. 2011;50(3):279-87. doi: 10.1016/j.ceca.2011.04.006. DOI: https://doi.org/10.1016/j.ceca.2011.04.006

Zhu T, Zhao Y, Hu H, Zheng Q, Luo X, Ling Y, et al. TRPM2 channel regulates cytokines production in astrocytes and aggravates brain disorder during lipopolysaccharide-induced endotoxin sepsis. Int Immunopharmacol. 2019 Oct;75:105836. doi: 10.1016/j.intimp.2019.105836. DOI: https://doi.org/10.1016/j.intimp.2019.105836

Uppal NN, Jhaveri M, Hong S, Shore-Lesserson L, Jhaveri KD, Izzedine H. Local anesthetics for the Nephrologist. Clin Kidney J. 2021;15(2):186-193. doi: 10.1093/ckj/sfab121. DOI: https://doi.org/10.1093/ckj/sfab121

Bhavna Gupta, Lalit Gupta. Anesthesia Consideration for Renal Disease. ARC J Anesth. 2018;3(1):9-14. DOI: dx.doi.org/10.20431/2455-9792.0301003 DOI: https://doi.org/10.20431/2455-9792.0301003

Park KK, Sharon VR. A Review of Local Anesthetics: Minimizing Risk and Side Effects in Cutaneous Surgery. Dermatol Surg. 2017;43(2):173-87. doi: 10.1097/DSS.0000000000000887. DOI: https://doi.org/10.1097/DSS.0000000000000887

Lili C, Shibata N, Yoshikawa Y, Takada K. Effect of glycerol-induced acute renal failure on the pharmacokinetics of lidocaine after transdermal application in rats. Biol Pharm Bull. 2003;26(8):1150-4. doi: 10.1248/bpb.26.1150. DOI: https://doi.org/10.1248/bpb.26.1150

Gallagher C, Tan JM, Foster CG. Lipid rescue for bupivacaine toxicity during cardiovascular procedures. Heart Int. 2010;5(1):e5. doi: 10.4081/hi.2010.e5. DOI: https://doi.org/10.4081/hi.2010.e5

Meuth SG, Budde T, Kanyshkova T, Broicher T, Munsch T, Pape HC. Contribution of TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 channels to the control of activity modes in thalamocortical neurons. J Neurosci. 2003;23(16):6460-9. doi: 10.1523/JNEUROSCI.23-16-06460.2003. DOI: https://doi.org/10.1523/JNEUROSCI.23-16-06460.2003

Gitman M, Barrington MJ. Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries. Reg Anesth Pain Med. 2018;43(2):124-30. doi: 10.1097/AAP.0000000000000721. DOI: https://doi.org/10.1097/AAP.0000000000000721

Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med. 2010;35(2):181-7. doi: 10.1097/aap.0b013e3181d2310b. DOI: https://doi.org/10.1097/AAP.0b013e3181d2310b

Tüzen AS, Arslan Yurtlu D, Çetinkaya AS, Aksun M, Karahan N. A Case of Late-Onset Local Anesthetic Toxicity Observed as Seizure Activity. Cureus. 2022;14(6):e25649. doi: 10.7759/cureus.25649. DOI: https://doi.org/10.7759/cureus.25649

Kien NT, Giang NT, Van Manh B, Cuong NM, Van Dinh N, Pho DC, et al. Successful intralipid-emulsion treatment of local anesthetic systemic toxicity following ultrasound-guided brachial plexus block: case report. Int Med Case Rep J. 2019;12:193-7. doi: 10.2147/IMCRJ.S207317. DOI: https://doi.org/10.2147/IMCRJ.S207317

Lavado P, Carvalho E, Almeida M, Taveira I, Pádua F. A Myriad of Symptoms After Spinal Anesthesia: A Case Report of Local Anesthetic Systemic Toxicity. Cureus. 2022;14(10):e29902. doi: 10.7759/cureus.29902. DOI: https://doi.org/10.7759/cureus.29902

Koo CH, Baik J, Shin HJ, Kim JH, Ryu JH, Han SH. Neurotoxic Effects of Local Anesthetics on Developing Motor Neurons in a Rat Model. J Clin Med. 2021;10(5):901. doi: 10.3390/jcm10050901. DOI: https://doi.org/10.3390/jcm10050901

Gao L, Yang Z, Zeng S, Li J, Wang N, Wang F. The potencies and neurotoxicity of intrathecal levobupivacaine in a rat spinal model: Effects of concentration. Pharmacol Res Perspect. 2023;11(4):e01116. doi: 10.1002/prp2.1116. DOI: https://doi.org/10.1002/prp2.1116

Zhang Y, Yan L, Cao Y, Kong G, Lin C. Long noncoding RNA BDNF-AS protects local anesthetic induced neurotoxicity in dorsal root ganglion neurons. Biomed Pharmacother. 2016;80:207-12. doi: 10.1016/j.biopha.2016.03.003. DOI: https://doi.org/10.1016/j.biopha.2016.03.003

Spitzer D, Wenger KJ, Neef V, Divé I, Schaller-Paule MA, Jahnke K, et al. Local Anesthetic-Induced Central Nervous System Toxicity during Interscalene Brachial Plexus Block: A Case Series Study of Three Patients. J Clin Med. 2021;10(5):1013. doi: 10.3390/jcm10051013. DOI: https://doi.org/10.3390/jcm10051013

Armstrong NC, Anderson RC, McDermott KW. Reelin: Diverse roles in central nervous system development, health and disease. Int J Biochem Cell Biol. 2019;112:72-5. doi: 10.1016/j.biocel.2019.04.009. DOI: https://doi.org/10.1016/j.biocel.2019.04.009

Tsuneura Y, Nakai T, Mizoguchi H, Yamada K. New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction. Int J Mol Sci. 2022;23(3):1829. doi: 10.3390/ijms23031829. DOI: https://doi.org/10.3390/ijms23031829

Dal Pozzo V, Crowell B, Briski N, Crockett DP, D'Arcangelo G. Reduced Reelin Expression in the Hippocampus after Traumatic Brain Injury. Biomolecules. 2020;10(7):975. doi: 10.3390/biom10070975. DOI: https://doi.org/10.3390/biom10070975

Huang S, Turlova E, Li F, Bao MH, Szeto V, Wong R, et al. Transient receptor potential melastatin 2 channels (TRPM2) mediate neonatal hypoxic-ischemic brain injury in mice. Exp Neurol. 2017;296:32-40. doi: 10.1016/j.expneurol.2017.06.023. DOI: https://doi.org/10.1016/j.expneurol.2017.06.023

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Published

2023-09-21

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Research Article

How to Cite

1.
Yılmaz N, Tepe M, Uludağ Öznur. Examination of the effect of bupivacaine on brain tissue in rats with induced experimental renal failure: Neurotoxicity of bupivacaine in renal failure. J Surg Med [Internet]. 2023 Sep. 21 [cited 2024 Apr. 23];7(9):598-601. Available from: https://jsurgmed.com/article/view/7924