Abstract
Objectives
To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats.
Methods
Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated.
Results
BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month.
Conclusion
BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR.
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References
Assi MA, Hezmee MNM, Sabri MYM, Rajion MA. The detrimental effects of lead on human and animal health. Vet World 2016;9:660.
Awaga M, Hamed NA, Hammad EE, Mohammed RH, Yassa H. Lead as a risk factor for attention deficit hyperactivity disorder (ADHD) in children. Zagazig J Forensic Med Toxicol 2020;18:21–33.
Naranjo VI, Hendricks M, Jones KS. Lead toxicity in children: an unremitting public health problem. Pediatr Neurol 2020;113:51–55.
Ilieva I, Sainova I. Free radicals and oxidative stress as the main mechanism of heavy metal toxicity in the male reprodutive system. Acta Morphol Anthropol 2022;29:69–79.
Mombeini MA, Kalantar H, Sadeghi E, Goudarzi M, Khalili H, Kalantar M. Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice. Naunyn Schmiedebergs Arch Pharmacol 2022;395:187–194.
Wang Y, Liu Y, Du X, Ma H, Yao J. The anti-cancer mechanisms of berberine: a review. Cancer Manag Res 2020;12:695.
Ahmed T, Abdollahi M, Daglia M, Nabavi SF, Nabavi SM. Berberine and neurodegeneration: a review of literature. Pharmacol Rep 2015;67:970–979.
Mohi-Ud-Din R, Mir RH, Wani TU, Shah AJ, Banday N, Pottoo FH. Berberine in the treatment of neurodegenerative diseases and nanotechnology enabled targeted delivery. Comb Chem 2022;25:616–633.
Pirmoradi Z, Yadegari M, Moradi A, Khojasteh F, Mehrjerdi FZ. Effect of berberine chloride on caspase-3 dependent apoptosis and antioxidant capacity in the hippocampus of the chronic cerebral hypoperfusion rat model. Iran J Basic Med Sci 2019;22:154.
Raeini AS, Hafizibarjin Z, Rezvani ME, Safari F, Aghda FA, Mehrjerdi FZ. Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion. Naunyn Schmiedebergs Arch Pharmacol 2020;393:581–589.
Aski ML, Rezvani ME, Khaksari M, Hafizi Z, Pirmoradi Z, Niknazar S, et al. Neuroprotective effect of berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia. Iran J Basic Med Sci 2018;21:53.
Nakhaee S, Mehrpour M, Mortazavi B, Weiss ST, Mehrpour O. Central nervous system infections versus lead toxicity in the differential diagnosis of encephalopathy. J Res Med Sci 2020;25:68.
da Silva DR, Bittencourt LO, Aragõ WA, Nascimento PC, Leão LK, Oliveira AC, et al. Long-term exposure to lead reduces antioxidant capacity and triggers motor neurons degeneration and demyelination in spinal cord of adult rats. Ecotoxicol Environ Saf 2020;194:110358.
Zucki F, Morata TC, Duarte JL, Ferreira MC, Salgado MH, Alvarenga KF. The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate. Braz J Otorhinolaryngol 2018;84:150–158.
Ortega DR, Esquivel DF, Ayala TB, Pineda B, Manzo SG, Quino JM, et al. Cognitive impairment induced by lead exposure during lifespan: mechanisms of lead neurotoxicity. Toxics 2021;9:23.
Sidhu GPS, Singh HP, Batish DR, Kohli RK. Effect of lead on oxidative status, antioxidative response and metal accumulation in Coronopus didymus. Plant Physiol Biochem 2016;105:290–296.
Chen H, Zhang W, Luo S, Li Y, Zhu Q, Xia Y, et al. Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway. Toxicology 2023;499:153654.
Bo JZ, Xue L, Li S, Yin JW, Li ZY, Wang X, et al. D-serine reduces memory impairment and neuronal damage induced by chronic lead exposure. Neural Regen Res 2021;16:836–841.
Okesola MA, Ajiboye BO, Oyinloye BE, Ojo OA. Neuromodulatory effects of ethyl acetate fraction of Zingiber officinale Roscoe extract in rats with lead-induced oxidative stress. J Integr Med 2019;17:125–131.
Bandaru LJ, Ayyalasomayajula N, Murumulla L, Challa S. Mechanisms associated with the dysregulation of mitochondrial function due to lead exposure and possible implications on the development of Alzheimer’s disease. Biometals 2022;35:1–25.
Han Q, Zhang W, Guo J, Zhu Q, Chen H, Xia Y, et al. Mitochondrion: a sensitive target for Pb exposure. J Toxicol Sci 2021;46:345–358.
Imenshahidi M, Hosseinzadeh H. Berberine and barberry (Berberis vulgaris): a clinical review. Phytother Res 2019;33:504–523.
Dang WT, Xu D, Zhou JG. Effect of berberine on activation of TLR4-NFκB signaling pathway and NLRP3 inflammasome in patients with gout. Chin J Integr Med 2023;29:10–18.
Cai Y, Xin Q, Lu J, Miao Y, Lin Q, Cong W, et al. A new therapeutic candidate for cardiovascular diseases: berberine. Front Pharmacol 2021;12:631100.
Zhao JV, Yeung WF, Chan YH, Vackova D, Leung JYY, Ip DKM, et al. Effect of berberine on cardiovascular disease risk factors: a mechanistic randomized controlled trial. Nutrients 2021;13:2550.
Rajasekhar K, Samanta S, Bagoband V, Murugan NA, Govindaraju T. Antioxidant berberine-derivative inhibits multifaceted amyloid toxicity. iScience 2020;23:101005.
Shou JW, Shaw PC. Therapeutic efficacies of berberine against neurological disorders: an update of pharmacological effects and mechanisms. Cells 2022;11:796.
Adefegha SA, Dada FA, Oyeleye SI, Oboh G. Effects of berberine on cholinesterases and monoamine oxidase activities, and antioxidant status in the brain of streptozotocin (STZ)-induced diabetic rats. J Basic Clin Physiol Pharmacol 2022;33:389–397.
Zhang JH, Zhang JF, Song J, Bai Y, Deng L, Feng CP, et al. Effects of berberine on diabetes and cognitive impairment in an animal model: the mechanisms of action. Am J Chin Med 2021;49:1399–1415.
Fan J, Zhang K, Jin Y, Li B, Gao S, Zhu J, et al. Pharmacological effects of berberine on mood disorders. J Cell Mol Med 2019;23:21–28.
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FZM and ASR actively participated in design, data analysis and collection, and writing of the article. FSZ, ZH, RM and FAA contributed in the data analysis and collection of the article. All the authors are fully aware of the final version of article. Article submission is done with the consent of all authors.
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Supported by the Research Project of Shahid Sadoughi University of Medical Sciences and Health Services (No. 5894)
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Mehrjerdi, F.Z., Raeini, A.S., Zebhi, F.S. et al. Berberine Hydrochloride Improves Cognitive Function and Hippocampal Antioxidant Status in Subchronic and Chronic Lead Poisoning. Chin. J. Integr. Med. (2024). https://doi.org/10.1007/s11655-024-3907-1
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DOI: https://doi.org/10.1007/s11655-024-3907-1