The Anti-obesity Agent d-norpseudoephedrine Protects Against Rotenone-induced Parkinson’s Disease in Mice
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Abstract
The effect of the ephedrine derivative D-norpseudoephedrine on rotenone-induced Parkinson’s disease in mice was studied. Mice received subcutaneous injections of rotenone (1.5 mg/kg, every other day for two weeks) and were treated with the vehicle, L-dopa (25 mg/kg) or pseudoephedrine at doses of 1.8, 5.4 and 10.8 mg/kg once daily orally. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) were determined and histopathological study of the brain was done. Motor testing included stair, wire hanging and wood walking tests. Results indicated that ompared with vehicle controls, rotenone caused significant increases in brain MDA and NO along with GSH depletion. Rotenone impaired neuromuscular strength, and motor balance and coordination. There were also marked decrease in size and number of substantia nigra pigmented cells and deeply stained neurons and karyorrhexis in the cerebral cortex and hippocampus. Treatment with pseudoephedrine reduced brain MDA, NO and increased GSH levels and improved motor performance. Furthermore, pseudoephedrine prevented substantia nigra dopaminergic cell death and neurodegeneration in the cortex and hippocampus brain regions in a dose-dependent manner. These data suggest that pseudoephedrine might prove of benefit adjunctive therapy of Parkinson’s disease.
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O. M.E.Abdel-Salam, M. E.-S. El-Shamarka, and N. Shaffie, “The Anti-obesity Agent d-norpseudoephedrine Protects Against Rotenone-induced Parkinson’s Disease in Mice”, Int.J.Halal.Res, vol. 4, no. 1, pp. 1-13, May 2022.
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References
Pankratz, N., & Foroud, T. (2007). Genetics of Parkinson disease. Genetics in Medicine, 9 (12), 801–811.
Alves, G., Forsaa, E.B., Pedersen, K.F., Gjerstad, M.D., & Larsen, J.P. (2008). Epidemiology of Parkinson’s disease. Journal of Neurology, 255 (Suppl 5), 18–32.
Berardelli, A., Rothwell, J.C., Thompson, P.D., & Hallett, M. (2001). Pathophysiology of bradykinesia in Parkinson’s disease. Brain, 124(Pt 11), 2131–2146.
Hughes, A.J., Daniel, S.E., Kilford, L., & Lees, A.J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson's disease: A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery and Psychiatry, 55(3), 181‒184.
Santens, P., Boon, P., Van Roost, D., & Caemaert, J. (2003).The pathophysiology of motor symptoms in Parkinson’s disease. Acta Neurologica Belgica,103(3), 129–134.
Wirdefeldt, K., Adami, H.O., Cole, P., Trichopoulos, D., & Mandel, J. (2011). Epidemiology and etiology of Parkinson's disease: a review of the evidence. European Journal of Epidemiology, 26 (Suppl 1), S1‒58.
Ritz, B.R., Paul, K.C., & Bronstein, J.M. (2016). Of pesticides and men: a California story of genes and environment in Parkinson's disease. Current Environmental Health Reports, 3, 40-52.
Sherer, T.B., Betarbet, R., Testa, C.M., Seo, B.B., Richardson, J.R., & Kim, J.H.( 2003). Mechanism of toxicity in rotenone models of Parkinson's disease. Journal of Neuroscience, 23(34),10756–64.
Nagatsu, T., & Sawada, M. (2007). Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. Journal of Neural Transmission, 72, 113-120.
Hermida-Ameijeiras, A., Méndez-Alvarez, E., Sánchez-Iglesias, S., Sanmartín-Suárez, C., & Soto-Otero, R. (2004). Autoxidation and MAO-mediated metabolism of dopamine as a potential cause of oxidative stress: role of ferrous and ferric ions. Neurochemistry International, 45(1), 103–116.
Dexter, D.T., Wells, F.R., Lees, A.J., Agid, F., Agid, Y., Jenner, P., & Marsden, C.D. (1989). Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. Journal of Neurochemistry, 52, 1830–1836.
Abdel-Salam, O.M.E. (2015). Drug therapy for Parkinson's disease: an update. World Journal of Pharmacology, 4(1), 117-143.
Eccles, R., Jawad, M.S.M., Jawad, S.S.M., Angello, G.T., & Druce, H.M. (2005) Efficacy and safety of single and multiple doses of pseudoephedrine in the treatment of nasal congestion associated with common cold. Journal of Rhinology, 19(1), 25–31.
Hauner, H., Hastreiter, L., Werdier, D., Chen-Stute, A., Scholze, J., & Blüher, M. (2017). Efficacy and safety of cathine (nor-pseudoephedrine) in the treatment of obesity: A randomized dose-finding study. Obesity Facts, 10(4), 407–419.
Kumarnsit, E., Harnyuttanakorn, P., Meksuriyen, D., Govitrapong, P., Baldwin, B.A., & Kotchabhakdi, N. (1999). Pseudoephedrine, a sympathomimetic agent, induces Fos-like immunoreactivity in rat nucleus accumbens and striatum. Neuropharmacology, 38(9), 1381-1387.
Wagner, G.C., Preston, K., Ricaurte, G.A., Schuster, C.R., & Seiden, L.S. (1982). Neurochemical similarities between d, l-cathinone and d-amphetamine. Drug and Alcohol Dependence, 9(4), 279–284.
Guantai, A.N., & Maitai, C.K. (1983). Metabolism of cathinone to d-norpseudoephedrine in humans. Journal of Pharmaceutical Sciences, 72(10), 1217-8.
Kalix, P. (1990). Pharmacological properties of the stimulant khat. Pharmacology & Therapeutics, 48(3), 397–416.
Abdel-Salam, O.M.E., Morsy, S.M.Y., Youness, E.R., Yassen, N.N., & Sleem, A.A. (2020). The effect of low dose amphetamine in rotenone-induced toxicity in a mice model of Parkinson’s disease. Iranian Journal of Basic Medical Sciences, 23(9), 1207-1217.
Paget, G.E., & Barnes, J.M. (1964). Toxicity testing. In: Laurence DR, Bacharach AL (eds) Evaluation of drug activities pharmacometics. Academic, London, pp 1–135.
Nair, V., & Turner, G.A. (1984). The thiobarbituric acid test for lipid peroxidation: structure of the adduct with malondialdehyde. Lipids, 19(10), 804-805.
Ellman, G.L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70‒77.
Archer, S. (1993). Measurement of nitric oxide in biological models. The FASEB Journal, 7(2), 349–60.
Crawley, J.N. (2017). What’s wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice. Second edition ed. Hoboken: Wiley.
Rogers, D.C., Campbell, C.A., Stretton, J.L., & Mackay, K.B. (1997). Correlation between motor impairment and infarct volume after permanent and transient middle cerebral artery occlusion in the rat. Stroke, 28(10), 2060–2065.
Baird, A.L., Meldrum, A., & Dunnett, S.B. (2001). The staircase test of skilled reaching in mice. Brain Research Bulletin, 54(2), 243–250.
Testa, C.M., Sherer, T.B., & Greenamyre, J.T. (2005). Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Brain Research. Molecular Brain Research, 134(1), 109–118.
Abdel-Salam, O.M.E., Omara, E.A., Youness, E.R., Khadrawy, Y.A., Mohammed, N.A., & Sleem, A.A. (2014). Rotenone-induced nigrostriatal toxicity is reduced by methylene blue. Journal of Neurorestoratology, 2(1), 65–80.
Li, N., Ragheb, K., Lawler, G., Sturgis, J., Rajwa, B., & Melendez, J.A. (2003). Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Journal of Biological Chemistry, 278(10), 8516-25.
Michelini, L.G., Figueira, T.R., Siqueira-Santos, E.S., & Castilho, R.F. (2015). Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain mitochondria from young-adult and old rats. Neuroscience Letters, 589, 25–30.
Gao, H.M., Liu, B., & Hong, J.S. (2003). Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. Journal of Neuroscience, 23(15), 6181–7.
Chang, C.Y., Song, M.J., Jeon, S.B., Yoon, H.J., Lee, D.K., & Kim, I.H. (2011). Dual functionality of myeloperoxidase in rotenone-exposed brain-resident immune cells. American Journal of Pathology, 179(2), 964–79.
Abdel-Salam, O.M.E., Sleem, A.A., Youness, E.R., Mohammed, N.A., Omara, E.A., & Shabana, M.E. (2019). Neuroprotective effects of the glutathione precursor N-acetylcysteine against rotenone-induced neurodegeneration. Reactive Oxygen Species, 8(22), 231–244.
Pacher, P., Beckman, J.S., & Liaudet, L. (2007). Nitric oxide and peroxynitrite in health and disease. Physiological Reviews, 87(1), 315–424.
He, Y., Imam, S.Z., Dong, Z., Jankovic, J., Ali, S.F., & Appel, S.H. (2003). Role of nitric oxide in rotenone induced nig.ro-striatal injury. Journal of Neurochemistry, 86(6), 1338–45.
Gao, B., Chang, C., Zhou, J., Zhao, T., Wang, C., & Li, C. (2015). Pycnogenol protects against rotenone-induced neurotoxicity in PC12 cells through regulating NF-κB-iNOS signaling pathway. DNA Cell Biolology, 34(10), 643-649.
Kanfer, I., Dowse, R., & Vuma, V. (1993). Pharmacokinetics of oral decongestants. Pharmacotherapy, 13(6 Pt 2), 116S-128S.
Drew, C.D., Knight, G.T., Hughes, D.T., & Bush, M. (1978). Comparison of the effects of D-(-)-ephedrine and L-(+)-pseudoephedrine on the cardiovascular and respiratory systems in man. British Journal of Clinical Pharmacology 6(3), 221-225.
Shi, C., Li, J. & Li, J. (2020). Ephedrine attenuates cerebral ischemia/reperfusion injury in rats through NF-kappaB signaling pathway. Human & Experimental Toxicology, 40(6), 994-1002.
Li, Q., Wu, J., Huang, L., Zhao, B., & Li, Q. (2021). Ephedrine ameliorates cerebral ischemia injury via inhibiting NOD-like receptor pyrin domain 3 inflammasome activation through the Akt/GSK3β/NRF2 pathway. Human & Experimental Toxicology, 40(12S), S540–S552.
Ruksee, N., Tongjaroenbuangam, W., Casalotti, S.O., & Govitrapong, P. (2008). Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats. BMC Neuroscience, 9,99.
World Drug Report. (2019). United Nations publication, Sales No. E.19.XI.8.
Hurwitz, B.E., Dietrich, W.D., McCabe, P.M., Alonso, O., Watson, B.D., & Ginsberg, M.D. (1991). Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex. Stroke, 22(5), 648-654.
Broadley, K.J. (2010). The vascular effects of trace amines and amphetamines. Pharmacology & Therapeutics, 125(3), 363–375.
Xie, Z., & Miller, G.M. (2008). Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. Journal of Pharmacology and Experimental Therapeutics, 325(2), 617-628.
Janssen, P.A.J., Leysen, J.E., Megens, A.A.H.P., & Awouters, F.H.L. (1999). Does phenylethylamine act as an endogenous amphetamine in some patients?. International Journal of Neuropsychopharmacology, 2(3), 229-240.
Alves, G., Forsaa, E.B., Pedersen, K.F., Gjerstad, M.D., & Larsen, J.P. (2008). Epidemiology of Parkinson’s disease. Journal of Neurology, 255 (Suppl 5), 18–32.
Berardelli, A., Rothwell, J.C., Thompson, P.D., & Hallett, M. (2001). Pathophysiology of bradykinesia in Parkinson’s disease. Brain, 124(Pt 11), 2131–2146.
Hughes, A.J., Daniel, S.E., Kilford, L., & Lees, A.J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson's disease: A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery and Psychiatry, 55(3), 181‒184.
Santens, P., Boon, P., Van Roost, D., & Caemaert, J. (2003).The pathophysiology of motor symptoms in Parkinson’s disease. Acta Neurologica Belgica,103(3), 129–134.
Wirdefeldt, K., Adami, H.O., Cole, P., Trichopoulos, D., & Mandel, J. (2011). Epidemiology and etiology of Parkinson's disease: a review of the evidence. European Journal of Epidemiology, 26 (Suppl 1), S1‒58.
Ritz, B.R., Paul, K.C., & Bronstein, J.M. (2016). Of pesticides and men: a California story of genes and environment in Parkinson's disease. Current Environmental Health Reports, 3, 40-52.
Sherer, T.B., Betarbet, R., Testa, C.M., Seo, B.B., Richardson, J.R., & Kim, J.H.( 2003). Mechanism of toxicity in rotenone models of Parkinson's disease. Journal of Neuroscience, 23(34),10756–64.
Nagatsu, T., & Sawada, M. (2007). Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. Journal of Neural Transmission, 72, 113-120.
Hermida-Ameijeiras, A., Méndez-Alvarez, E., Sánchez-Iglesias, S., Sanmartín-Suárez, C., & Soto-Otero, R. (2004). Autoxidation and MAO-mediated metabolism of dopamine as a potential cause of oxidative stress: role of ferrous and ferric ions. Neurochemistry International, 45(1), 103–116.
Dexter, D.T., Wells, F.R., Lees, A.J., Agid, F., Agid, Y., Jenner, P., & Marsden, C.D. (1989). Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. Journal of Neurochemistry, 52, 1830–1836.
Abdel-Salam, O.M.E. (2015). Drug therapy for Parkinson's disease: an update. World Journal of Pharmacology, 4(1), 117-143.
Eccles, R., Jawad, M.S.M., Jawad, S.S.M., Angello, G.T., & Druce, H.M. (2005) Efficacy and safety of single and multiple doses of pseudoephedrine in the treatment of nasal congestion associated with common cold. Journal of Rhinology, 19(1), 25–31.
Hauner, H., Hastreiter, L., Werdier, D., Chen-Stute, A., Scholze, J., & Blüher, M. (2017). Efficacy and safety of cathine (nor-pseudoephedrine) in the treatment of obesity: A randomized dose-finding study. Obesity Facts, 10(4), 407–419.
Kumarnsit, E., Harnyuttanakorn, P., Meksuriyen, D., Govitrapong, P., Baldwin, B.A., & Kotchabhakdi, N. (1999). Pseudoephedrine, a sympathomimetic agent, induces Fos-like immunoreactivity in rat nucleus accumbens and striatum. Neuropharmacology, 38(9), 1381-1387.
Wagner, G.C., Preston, K., Ricaurte, G.A., Schuster, C.R., & Seiden, L.S. (1982). Neurochemical similarities between d, l-cathinone and d-amphetamine. Drug and Alcohol Dependence, 9(4), 279–284.
Guantai, A.N., & Maitai, C.K. (1983). Metabolism of cathinone to d-norpseudoephedrine in humans. Journal of Pharmaceutical Sciences, 72(10), 1217-8.
Kalix, P. (1990). Pharmacological properties of the stimulant khat. Pharmacology & Therapeutics, 48(3), 397–416.
Abdel-Salam, O.M.E., Morsy, S.M.Y., Youness, E.R., Yassen, N.N., & Sleem, A.A. (2020). The effect of low dose amphetamine in rotenone-induced toxicity in a mice model of Parkinson’s disease. Iranian Journal of Basic Medical Sciences, 23(9), 1207-1217.
Paget, G.E., & Barnes, J.M. (1964). Toxicity testing. In: Laurence DR, Bacharach AL (eds) Evaluation of drug activities pharmacometics. Academic, London, pp 1–135.
Nair, V., & Turner, G.A. (1984). The thiobarbituric acid test for lipid peroxidation: structure of the adduct with malondialdehyde. Lipids, 19(10), 804-805.
Ellman, G.L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70‒77.
Archer, S. (1993). Measurement of nitric oxide in biological models. The FASEB Journal, 7(2), 349–60.
Crawley, J.N. (2017). What’s wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice. Second edition ed. Hoboken: Wiley.
Rogers, D.C., Campbell, C.A., Stretton, J.L., & Mackay, K.B. (1997). Correlation between motor impairment and infarct volume after permanent and transient middle cerebral artery occlusion in the rat. Stroke, 28(10), 2060–2065.
Baird, A.L., Meldrum, A., & Dunnett, S.B. (2001). The staircase test of skilled reaching in mice. Brain Research Bulletin, 54(2), 243–250.
Testa, C.M., Sherer, T.B., & Greenamyre, J.T. (2005). Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Brain Research. Molecular Brain Research, 134(1), 109–118.
Abdel-Salam, O.M.E., Omara, E.A., Youness, E.R., Khadrawy, Y.A., Mohammed, N.A., & Sleem, A.A. (2014). Rotenone-induced nigrostriatal toxicity is reduced by methylene blue. Journal of Neurorestoratology, 2(1), 65–80.
Li, N., Ragheb, K., Lawler, G., Sturgis, J., Rajwa, B., & Melendez, J.A. (2003). Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Journal of Biological Chemistry, 278(10), 8516-25.
Michelini, L.G., Figueira, T.R., Siqueira-Santos, E.S., & Castilho, R.F. (2015). Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain mitochondria from young-adult and old rats. Neuroscience Letters, 589, 25–30.
Gao, H.M., Liu, B., & Hong, J.S. (2003). Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. Journal of Neuroscience, 23(15), 6181–7.
Chang, C.Y., Song, M.J., Jeon, S.B., Yoon, H.J., Lee, D.K., & Kim, I.H. (2011). Dual functionality of myeloperoxidase in rotenone-exposed brain-resident immune cells. American Journal of Pathology, 179(2), 964–79.
Abdel-Salam, O.M.E., Sleem, A.A., Youness, E.R., Mohammed, N.A., Omara, E.A., & Shabana, M.E. (2019). Neuroprotective effects of the glutathione precursor N-acetylcysteine against rotenone-induced neurodegeneration. Reactive Oxygen Species, 8(22), 231–244.
Pacher, P., Beckman, J.S., & Liaudet, L. (2007). Nitric oxide and peroxynitrite in health and disease. Physiological Reviews, 87(1), 315–424.
He, Y., Imam, S.Z., Dong, Z., Jankovic, J., Ali, S.F., & Appel, S.H. (2003). Role of nitric oxide in rotenone induced nig.ro-striatal injury. Journal of Neurochemistry, 86(6), 1338–45.
Gao, B., Chang, C., Zhou, J., Zhao, T., Wang, C., & Li, C. (2015). Pycnogenol protects against rotenone-induced neurotoxicity in PC12 cells through regulating NF-κB-iNOS signaling pathway. DNA Cell Biolology, 34(10), 643-649.
Kanfer, I., Dowse, R., & Vuma, V. (1993). Pharmacokinetics of oral decongestants. Pharmacotherapy, 13(6 Pt 2), 116S-128S.
Drew, C.D., Knight, G.T., Hughes, D.T., & Bush, M. (1978). Comparison of the effects of D-(-)-ephedrine and L-(+)-pseudoephedrine on the cardiovascular and respiratory systems in man. British Journal of Clinical Pharmacology 6(3), 221-225.
Shi, C., Li, J. & Li, J. (2020). Ephedrine attenuates cerebral ischemia/reperfusion injury in rats through NF-kappaB signaling pathway. Human & Experimental Toxicology, 40(6), 994-1002.
Li, Q., Wu, J., Huang, L., Zhao, B., & Li, Q. (2021). Ephedrine ameliorates cerebral ischemia injury via inhibiting NOD-like receptor pyrin domain 3 inflammasome activation through the Akt/GSK3β/NRF2 pathway. Human & Experimental Toxicology, 40(12S), S540–S552.
Ruksee, N., Tongjaroenbuangam, W., Casalotti, S.O., & Govitrapong, P. (2008). Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats. BMC Neuroscience, 9,99.
World Drug Report. (2019). United Nations publication, Sales No. E.19.XI.8.
Hurwitz, B.E., Dietrich, W.D., McCabe, P.M., Alonso, O., Watson, B.D., & Ginsberg, M.D. (1991). Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex. Stroke, 22(5), 648-654.
Broadley, K.J. (2010). The vascular effects of trace amines and amphetamines. Pharmacology & Therapeutics, 125(3), 363–375.
Xie, Z., & Miller, G.M. (2008). Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. Journal of Pharmacology and Experimental Therapeutics, 325(2), 617-628.
Janssen, P.A.J., Leysen, J.E., Megens, A.A.H.P., & Awouters, F.H.L. (1999). Does phenylethylamine act as an endogenous amphetamine in some patients?. International Journal of Neuropsychopharmacology, 2(3), 229-240.