A review on the potential benefits of phosphodiesterase inhibitors in various models of toxicities in animals

Asian Journal of Animal and Veterinary Advances

Volumn 7, Issue 3, 2012, Pages 210-224

  Ghiasi, Sima ^a,b   Ghiasi, Sindokht ^c   Abdollahi, Mohammad ^a,b  

^a TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c URMIA UNIVERSITY   (Iran)

Author keywords

Adverse effects; cAMP; cGMP; Phosphodiesterase inhibitors; Toxicity

Indexed keywords

ANIMALIA;

EID: 84855926234     PISSN: 16839919     EISSN: None     Source Type: Journal    
DOI: 10.3923/ajava.2012.210.224     Document Type: Review

References (102)

1. Abdel-Salam, O.M., F.H. Oraby and N.S. Hassan, 2007. Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats. Acta Biol. Hung., 58: 411-419.
2. Abdollahi, M., A.R. Dehpour and P. Kazemian, 2000. Interaction of cadmium with nitric oxide in rat submandibulary gland function. Pharmacol. Res., 42: 591-597.
3. Abdollahi, M., A. Bahreini-Moghadam, B. Emami, F. Fooladian and K. Zafari, 2003a. Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva. Comp. Biochem. Physiol. C. Toxicol. Pharmacol., 135: 331-336.
4. Abdollahi, M., F. Fooladian, B. Emami, K. Zafari and A. Bahreini-Moghadam, 2003b. Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva. Hum. Exp. Toxicol., 22: 587-592.
5. Aghababaeian, R., M. Ghazi-Khansari, K. Abdi, F. Taghadosinejad and M. Abdollahi, 2005. Protective effects of sildenafil and dipyridamol from lead-induced lipid peroxidation in perfused rat liver. Int. J. Pharmacol., 1: 157-160.
6. Akhgari, M., M. Abdollahi, A. Kebryaeezadeh, R. Hosseini and O. Sabzevari, 2003. Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for Subchronic toxicity of malathion in blood and liver of rats. Hum. Exp. Toxicol., 22: 205-211.
7. Alousi, A.A., J.M. Canter, M.J. Montenaro, D.J. Fort and R.A. Ferrari, 1983. Cardiotonic activity of milrinone, a new and potent cardiac bipyridine, on the normal and failing heart of experimental animals. J. Cardiovasc. Pharmacol., 5: 792-803.
8. Alousi, A.A., J.M. Canter and D.J. Fort, 1985. The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog. Cardiovasc. Res., 19: 483-494.
9. Amirkabirian, N., F. Teimouri, H. Esmaily, A. Mohammadirad, A. Aliahmadi and M. Abdollahi, 2007. Protection by pentoxifylline of diazinon-induced toxic stress in rat liver and muscle. Toxicol. Mech. Methods, 17: 215-221.
10. Amsallem, E., C. Kasparian, G. Haddour, J.P. Boissel and P. Nony, 2005. Phosphodiesterase III inhibitors for heart failure. Cochrane Database Syst. Rev., 10.1002/14651858.CD002230.pub2
11. Anttila, P. and H. Vapaatalo, 1972. Decreased toxicity of d-tubocurarine after pretreatment with drugs elevating the intracellular level of c-AMP in mice. Naunyn-Schmiedeberg's Arch. Pharmacol, 273: 175-178.
12. Azadbar, M, A. Ranjbar, A. Hosseini-Tabatabaei, A. Golestani, M. Baeeri, M. Sharifzadeh and M. Abdollahi, 2009. Interaction of phosphodiesterase 5 inhibitor with malathion on rat brain mitochondrial-bound hexokinase activity. Pestic. Biochem. Physiol, 95: 121-125.
13. Beavo, J.A, M. Conti and R.J. Heaslip, 1994. Multiple cyclic nucleotide phosphodiesterases. Mol. Pharmacol, 46: 399-405.
14. Beshay, E, F. Croze and G.J. Prud'homme, 2001. The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo. Clin. Immunol, 98: 272-279.
15. Boswell-Smith, V, D. Spina and C.P. Page, 2006. Phosphodiesterase inhibitors. Br. J. Pharmacol, 147: S252-S257.
16. Bristow, M.R, M.E. Billmgham, J.W. Mason and J.R. Daniels, 1978. Clinical spectrum of anthracycline antibiotic cardiotoxicity. Cancer Treat. Rep, 62: 873-879.
17. Clarkson, C.W. and L.M. Hondeghem, 1985. Mechanism for bupivacaine depression of cardiac conduction: Fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology, 62: 396-405.
18. Commins, D.L, G. Vosmer, R.M. Virus, W.L. Woolverton, C.R. Schuster and L.S. Seiden, 1987. Biochemical and histological evidence that methylene dioxy methyl amphetamine (MDMA) is toxic to neurons in the rat brain. J. Pharmacol. Exp. Ther, 241: 338-345.
19. Coyle, D.E. and N. Sperelakis, 1987. Bupivacaine and lidocaine blockade of calcium-mediated slow action potentials in guinea pig ventricular muscle. JPET, 242: 1001-1005.
20. DeMarch, Z, C. Giampa, S. Patassini, A. Martorana, G. Bernardi and F.R. Fusco, 2007. Beneficial effects of rolipram in a quinolinic acid model of striatal excitotoxicity. Neurobiol. Dis, 25: 266-273.
21. DeWitt, C.R. and J.C. Waksman, 2004. Pharmacology, pathophysiology and management of calcium channel blocker and P-blocker toxicity. Toxicol. Rev, 23: 223-238.
22. Decker, K, 1990. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur. J. Biochem, 192: 245-261.
23. Degerman, E, P. Belfrage, A.H. Newman, K.C. Rice and V.C. Manganiello, 1987. Purification of the putative hormone-sensitive cyclic AMP phosphodiesterase from rat adipose tissue using a derivative of cilostamide as a novel affinity ligand. J. Biol. Chem, 262: 5797-5807.
24. Dehmer, T, J. Lindenau, S. Haid, J. Dichgans and J.B. Schulz, 2000. Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J. Neurochem, 74: 2213-2216.
25. Dousa, T.P, 1999. Cyclic-3,-5,-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney. Kidney Int., 55: 29-62.
26. Erdogan, S, S. Celik, O. Aslantas, T. Kontas and S. Ocak, 2007. Elevated cAMP levels reverse Brucella melitensis-induced lipid peroxidation and stimulate IL-10 transcription in rats. Res. Vet. Sci, 82: 181-186.
27. Erdogan, S, O. Aslantas, S. Celik and E. Atik, 2008. The effects of increased cAMP content on inflammation, oxidative stress and PDE4 transcripts during Brucella melitensis infection. Res. Vet. Sci., 84: 18-25.
28. Essayan, D.M, 2001. Cyclic nucleotide phosphodiesterases. J. Allergy Clin. Immunol, 108: 671-680.
29. Fisher, P.W., F. Salloum, A. Das, H. Hyder and R.C. Kukreja, 2005. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation, 111: 1601-1610.
30. Folcik, V.A., T. Smith, S. O'Bryant, J.A. Kawczak and B. Zhu et al., 1999. Treatment with BBB022A or rolipram stabilizes the blood-brain barrier in experimental autoimmune encephalomyelitis: An additional mechanism for the therapeutic effect of type IV phosphodiesterase inhibitors. J. Neuroimmunol., 97: 119-128.
31. Frye, C.A. and M.E. Rhodes, 2003. Zaprinast, a phosphodiesterase 5 inhibitor, overcomes sexual dysfunction produced by fluoxetine, a selective serotonin reuptake inhibitor in hamsters. Neuropsychopharmacology, 28: 310-316.
32. Ghafour-Rashidi, Z., E. Dermenaki-Farahani, A. Aliahmadi, H. Esmaily, A. Mohammadirad, S.N. Ostad and M. Abdollahi, 2007. Protection by cAMP and cGMP phosphodiesterase inhibitors of diazinon-induced hyperglycemia and oxidative/nitrosative stress in ratlangerhans islets cells: Molecular evidence for involvement of non-cholinergic mechanisms. Pest. Biochem. Physiol., 87: 261-270.
33. Ghosh, R., O. Sawant, P. Ganpathy, S. Pitre and V.J. Kadam, 2009. Phosphodiesterase inhibitors: their role and implications. IJPTR, 1: 1148-1160.
34. Green, A.R., A.O. Mechan, J.M. Elliott, E. O'Shea and M.I. Colado, 2003. The pharmacology and clinical pharmacology of 3,4-methylene-dioxymethamphetamine (MDMA, ecstasy). Pharmacol. Rev, 55: 463-508.
35. Harrison, S.A, D.H. Reifsnyder, B. Gallis, G.C. Cadd and J.A. Beavo, 1986. Isolation and characterization of bovine cardiac muscle cGMP-inhibited phosphodiesterase: A receptor for new cardiotonic drugs. Mol. Pharmacol, 29: 506-514.
36. Herrerias, J.M, J.M. Esteban, A.M. Caballero-Plasencia, M. Valenzuela-Barranco and V. Motilva et al., 2003. Preventive effect of zaprinast and 3-Isobutyl, 1-methylxanthine (phosphodiesterase inhibitors) on gastric injury induced by nonsteroidal anti-inflammatory drugs in rats. Dig. Dis. Sci, 48: 986-991.
37. Holbrook, M, N. Gozzard, T. James, G. Higgs and B. Hughes, 1996. Inhibition of bronchospasm and ozone-induced airway hyperresponsiveness in the guinea-pig by CDP840, a novel phosphodiesterase type 4 inhibitor. Br. J. Pharmacol, 118: 1192-1200.
38. Hood, W.B, 1989. Controlled and uncontrolled studies of phosphodiesterases 3 inhibitors in contemporary cardiovascular medicine. Am. J. Cardiol, 63: A46-A53.
39. Hosogai, N, J. Seki and T. Goto, 2001. Reciprocal regulation of cyclic GMP content by cyclic GMP-phosphodiesterase and guanylate cyclase in SHR with CsA-induced nephrotoxicity. Br. J. Pharmacol, 134: 995-1002.
40. Hosogai, N, M. Tomita, K. Hamada, T. Ogawa, J. Hirosumi, T. Manda and S. Mutoh, 2003. Phosphodiesterase type 5 inhibition ameliorates nephrotoxicity induced by cyclosporin A in spontaneous hypertensive rats. Eur. J. Pharmacol, 477: 171-178.
41. Houslay, M.D. and D.R. Adams, 2003. PDE4 cAMP phosphodiesterases: Modular enzymes that orchestrate signaling cross-talk, desensitization and compartmentalization. Biochem. J, 370: 1-18.
42. Huang, Z, Y. Ducharme, D. Macdonald and A. Robichaud, 2001. The next generation of PDE4 inhibitors. Curr. Opm. Chem. Biol, 5: 432-438.
43. Hulley, P, J. Hartikka, S. AbdelAl, P. Engels and H.R. Buerki et al, 1995. Inhibitors of type IV phosphodiesterases reduce the toxicity of MPTP in substantia nigra neurons in vivo. Eur. J. Neurosci, 7: 2431-2440.
44. 2+/calmodulin-dependent multifunctional protein kinase. J. Biol. Chem., 265: 8975-8978.
45. Jacob, C, C. Szilagyi, J.M. Allen, C. Bertrand and V. Lagente, 2004. Role of PDE4 in superoxide anion generation through p44/42MAPK regulation: A cAMP and a PKA-independent mechanism. Br. J. Pharmacol., 143: 257-268.
46. Jeon, Y.H, Y.S. Heo, CM. Kim, Y.L. Hyun, T.G. Lee, S. Ro and J.M. Cho, 2005. Phosphodiesterase: Overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell Mol. Life Sci., 62: 1198-1220.
47. Kaneko, Y., K. Takashima, N. Suzuki and K. Yamana, 2007. Effects of theophylline on chronic inflammatory lung injury induced by LPS exposure in guinea pigs. Allergol. Int., 56: 445-456.
48. Karakaya, K., V. Hanci, S. Bektas, M. Can and H.B. Ucan et al., 2009. Mitigation of indomethacin- induced gastric mucosal lesions by a potent specific type 5 phosphodiesterase inhibitor. World J. Gastroenterol., 15: 5091-5096.
49. Khoshakhlagh, P., M. Bahrololoumi-Shapourabadi, A. Mohammadirad, L. Ashtaral-Nakhai, B. Minaie and M. Abdollahi, 2007. Beneficial effect of phosphodiesterase-5 inhibitor in experimental inflammatory bowel disease; molecular evidence for involvement of oxidative stress. Toxicol. Mech. Methods, 17: 281-288.
50. Koka, S., A. Das, S.G. Zhu, D. Durrant, L. Xi and R.C. Kukreja, 2010. Long-acting phosphodiesterase-5 inhibitor tadalafil attenuates doxorubicin-induced cardiomyopathy without interfering with chemotherapeutic effect. J. Pharmacol. Exp. Ther., 334: 1023-1030.
51. Kondo, N., S. Shibita, I. Kodama and K. Yamada, 1983. Electrical and mechanical effects of amrinone on isolated guinea pigs ventricular muscle. J. Cardiovasc. Pharmacol., 5: 903-912.
52. Kotera, J., K. Fujishige and K. Omori, 2000. Immunohistochemical localization of cGMP-binding cGMP-specific phosphodieterase (PDE 5) in rat tissues. J. Histochem. Cytochem., 48: 685-693.
53. Kotera, J., T. Sasaki and K. Omori, 2005. Recent progress in cyclic nucleotide phosphodiesterase research: Isozymes, function and inhibitors. Nihon. Yakurigaku. Zasshi., 126: 121-127.
54. Kwon, G., H. Jr. Hill, J.A. Corbette and M.L. Daniel, 1997. Effects of aspirin on nitric oxide formation and denovo protein synthesis by RIN% F cells and rat islets. Mol. Pharmacol., 52: 388-405.
55. Lad, P.M., B.J. Goldberg, P.A. Smiley and C.V. Olson, 1985. Receptor specific threshold effects of cyclic AMP are involved in the regulation of enzyme release and superoxide production from human neutrophils. Biochim. Biophys. Acta (BBA)., 846: 286-295.
56. Landon, E.J., R.J. Naukam and B.V. Rama-Sastry, 1986. Effects of calcium channel blocking agents on calcium and centrilobular necrosis in the liver of rats treated with hepatotoxic agents. Biochem. Pharmacol., 35: 697-705.
57. Lefrak, E.A., J. Pitha, S. Rosenheim and J.A. Gottlieb, 1973. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer., 32: 302-314.
58. Lindeman J.P., J. Bailey and A.M. Watanabe, 1983. Potential biochemical mechanisms for regulation of slow inward current: Theoretical basis for drug action. Am. Heart. J., 103: 746-756.
59. Lindgren, L., T. Randell, N. Suzuki, J. Kytta, A. Yli-Hankala and P.H. Rosenberg, 1992. The effect of Amrinon on recovery from severe bupivacaine intoxication in pigs Anesthesiology., 77: 309-315.
60. Lopez-Belmonte, J., B.J. Whittle and S. Moncada, 1993. The actions of nitricoxide donors in the prevention or induction of injury to the rat gastric mucosa. Br. J. Pharmacol., 108: 73-78.
61. Lugnier, C, 2006. Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific therapeutic agents. Pharmacol. Ther., 109: 366-398.
62. Lynch, C, 1986. Depression of myocardial contractility in vitro by bupivacaine, Etidocaine and lidocaine. Anesth. Analg., 65: 551-559.
63. Lynch, M.J., E.V. Hill and M.D. Houslay, 2006. Intracellular targeting of phosphodiesterase-4 underpins compartmentalized cAMP signaling. Curr. Topics. Dev. Biol., 75: 225-259.
64. Macphee, C.H., S.A. Harrison and J.A. Beavo, 1986. Immunological identification of the major platelet low-Km cAMP phosphodiesterase: Probable target for anti-thrombotic agents. Proc. Natl. Acad. Sci. USA, 83: 6660-6663.
65. Matsuhashi, T, M. Otaka, M. Odashima, M. Jin and K. Komatsuk et al., 2005. Specific type IV phosphodiesterase inhibit or ameliorates thioacet amide-induced liver injury in rats. J. Gastroenterol. Hepatol, 20: 135-140.
66. Matussek, A, J. Lauber, A. Bergau, W. Hansen and M. Rohde et al., 2003. Molecular and functional analysis of Shiga toxin induced response patterns in human vascular endothehalcells. Blood, 102: 1323-1332.
67. Melek, I.M, S. Erdogan, S. Celik, O. Aslantas and T. Duman, 2006. Evaluation of oxidative stress and inflammation in long term Brucella melitensis infection. Mol. Cell. Biochem, 293: 203-209.
68. Milani, E, S. Nikfar, R. Khorasani, M.J. Zamani and M. Abdollahi, 2005. Reduction of diabetes-induced oxidative stress by phosphodiestrase inhibitors in rats. Comparative Biochem. Physiol, 140 C: 251-255.
69. Milatovic, D, R.C. Gupta and M. Aschner, 2006. Anticholinesterase toxicity and oxidative stress. Sci. World. J, 28: 295-310.
70. Mohammadi, M, S. Atashpour, N. Pourkhahh, A. Nih-Ahmadabadi and M. Baeeri et al, 2011. Comparative improvement in function of isolated rat langerhans islets by various phosphodiesterase 3, 4 and 5 inhibitors. Asian J. Anim. Vet. Adv., 6: 1233-1240.
71. Muller, T, P. Engels and J.R. Fozard, 1996. Subtypes of the type4 cAMP phosphodiesterases: Structure, regulation and selective inhibition. Trends. Pharmacol. Sci, 17: 294-298.
72. Myers, B.D, 1986. Cyclosporine nephrotoxicity. Kidney Int., 30: 964-974.
73. Obrig, T.G, 1997. Shiga toxin mode of action in E. coli 0157: H7 disease. Front. Biosci, 15: d635-d642.
74. Okayama, A, K. Mikasa, N. Matsui, N. Higashi, M. Miyamoto and E. Kita, 2004. An interventional approach to block brain damage caused by Shiga toxin-producing Escherichia coli infection, by use of a combination of phosphodiesterase inhibitors. J. Infec. Dis, 190: 2129-2136.
75. Paton, J.C. and A.W. Paton, 1998. Pathogenesis and diagnosis of shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev, 11: 450-479.
76. Pere, A.K, L. Krogerus, E.M. Mervaala, J. Laakso and H. Karppanen et al., 1998. Detrimental effect of dietary sodium and beneficial effect of dietary magnesium on glomerular changes in cyclosporin-a treated spontaneously hypertensive rats. Nephrol. Dial. Transplantation, 13:904-910.
77. Polte, T, A. Hemmerle, G. Berndt, N. Grosser, A. Abate and H. Schroder, 2002. Atrial natriuretic peptide reduces cyclosporin toxicity in renal cells: Role of cGMP and heme oxygenase-1. Free Radical Biol. Med, 32: 56-63.
78. Puetra, E., I. Hervias, B. Goni-Allo, B. Lasheras, J. Jordan and N. Aguirre, 2009. Phosphodiesterase 5 inhibitors prevent 3,4-methylenedioxymethamphetamine-induced 5-HT deficits in the rat. J. Neurochem., 108: 755-766.
79. Radfar, M, B. Larrjam, M. Hadjibabaie, B. Rajabipour, A. Mojtahedi and M. Abdollahi, 2005. Effects of pentoxifylline on oxidative stress and levels of EGF and NO in blood of diabetic type-2 patients: A randomized, double-blind placebo-controlled clinical trial. Biomed. Pharmacother., 59: 302-306.
80. Rahimi, R., S. Ghiasi, H. Azimi, S. Fakhari and M. Abdollahi, 2010. A review of the herbal phosphodiesterase inhibitors: Future perspective of new drugs. Cytokine, 49: 123-129.
81. Ranjbar, A., M.H. Ghahremani, M. Sharifzadeh, A. Golestani, M. Ghazi-Khansari, M. Baeeri and M. Abdollahi, 2010. Protection by pentoxifylline of malathion-induced toxic stress and mitochondrial damage in rat brain. Hum. Exp. Toxicol., 29: 851-864.
82. Rezvanfar, M.A., M.A. Rezvanfar, A. Ranjbar, M. Baeeri, A. Mohammadirad and M. Abdollahi, 2010. Biochemical evidence on positive effects of rolipram a phosphodiesterase-4 inhibitor in malathion-induced toxic stress in rat blood and brain mitochondria. Pesticide Biochem. Physiol., 98: 135-143.
83. Romero, G., B. Lasheras, L. Sainz-Suberviola and E. Cenarruzabeitia, 1994. Protective effects of calcium channel blockers in carbon tetrachloride-induced liver toxicity. Life Sci., 55: 981-990.
84. Rotella, D.P., 2002. Phosphodiesterase 5 inhibitors: Current status and potential applications. Nat. Rev. Drug Discovery, 1: 674-682.
85. Ruth, P., 1999. Cyclic GMP-dependent protein kinases: Understanding in vivo functions by gene targeting. Pharmacol. Ther., 82: 355-372.
86. Saitoh, K., Y. Hirabayashi, R. Shimizu and H. Fukuda, 1995. Amrinon is superior to epinephrine in reversing bupivacaine-induced cardiovascular depression in sevoflurane-anesthetized dogs. Anesthesiology, 83: 127-133.
87. Sato, S., M.H. Tsuji, N. Okubo and H. Naito, 1994. Milrinone versus glucagon: Comparative hemodynamic effects in canine propranolol poisoning. J. Toxicol. Clin. Toxicol., 32: 277-289.
88. Scarpignato, C, 1995. Nonsteroidal anti-inflammatory drugs: How do they damage gastroduodenal mucosa? Digestive Dis., 13: 9-39.
89. Sekut, L., D. Yarnall, S.A. Stimpson, L.S. Noel and R. Bateman-Fite et al., 1995. Anti-inflammatory activity of phosphodiesterase (PDE)-IV inhibitors in acute and chronic models of inflammation. Clin. Exp. Immunol, 100: 126-132.
90. 2+ influx in myocardial cells by beta adrenergic receptors, cyclic nucleotides and phosphorylation. Mol. Cell. Biochem, 82: 19-28.
91. Steffan, J.S, A. Kazantsev, O. Spasic-Boskovic, M. Greenwald and Y.Z. Zhu et al., 2000. The Huntington's disease protein interacts with p53 and CREB binding protein and represses transcription. Proc. Nat. Acad. Sci, 97: 6763-6768.
92. Teimouri, F, N. Amirkabirian, H. Esmaily, A. Mohammadirad, A. Aliahmadi and M. Abdollahi, 2006. Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress. Hum. Exp. Toxicol, 25: 697-703.
93. Torphy, T.J, 1998. Phosphodiesterase isozymes: Molecular targets for novel antiasthma agents. Am. J. Respir. Crit. Care Med, 157: 351-370.
94. Toward, T.J. and K.J. Broadley, 2002. Goblet cell hyperplasia, airway function and leukocyte infiltration after chronic lipopolysaccharide exposure in conscious Guinea Pigs: Effects of Rolipram and Dexamethasone. J. Pharmacol. Exp. Ther, 302: 814-821.
95. Travadi, J.N. and S.K. Patole, 2003. Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: A review. Pediatr. Pulmonol., 36: 529-535.
96. Trevisan, R., M. Uliano-Silva, P. Pandolfo, J.L. Franco and P.S. Brocardo et al., 2008. Antioxidant and acetylcholinesterase response to repeated malathion exposure in rat cerebral cortex and hippocampus. Basic Clin. Pharmacol. Toxicol., 102: 365-369.
97. Tripp, M.A. and B.L. Tepperman, 1995. Effect of nitric oxide on integrity, blood flow and cyclic GMP levels in the rat gastric mucosa: Modulation by sialoadenectomy. Br. J. Pharmacol, 115:344-348.
98. Uckert, S, A. Kuthe, C.G. Stief and U. Jonas, 2001. Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male erectile dysfunction. World J. Urol, 19: 14-22.
99. Wu, D.C, P. Teismann, K. Tieu, M. Vila, V. Jackson-Lewis, H. Ischiropoulos and S. Przedborski, 2003. NADPH oxidase mediates oxidative stress in the l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc. Nat. Acad. Sci, 100: 6145-6150.
100. +channels: physiological role and pharmacology. Curr. Med. Chem, 10: 649-661.
101. Yang, L, N.Y. Calingasan, B.J. Lorenzo and M.F. Beal, 2008. Attenuation of MPTP neurotoxicity by rolipram, a specific inhibitor of phosphodiesterase IV. Exp. Neurol, 211: 311-314.
102. Zhong, Z, G.E. Arteel, H.D. Connor, M. Yin and M.V. Frankenberg et al, 1998. Cyclosporin A increases hypoxia and free radical production in rat kidneys: Prevention by dietary glycine. Am. J. Physiol, 275: F595-F604.