Introduction. Lamivudine is a nucleoside reverse transcriptase inhibitor antiretroviral agent used in the treatment of human immunodeficiency virus type 1 infection. This study was to investigate the effects of coadministration of neurovite and lamivudine on the histomorphology of the cerebellum of Wistar rats. Materials and Methods. Twenty Wistar rats were divided equally into four groups. Group A animals were the control treated with distilled water. Groups B, C, and D animals were treated, respectively, with therapeutic dose of lamivudine (4.28？mg/kg), a combination of lamivudine (4.28？mg/kg) and neurovite (7.05？mg/kg), and neurovite (7.05？mg/kg) alone, daily. The rats were sacrificed using chloroform inhalation, processed, and stained using H&E method. Results. There was severe cellular degeneration with dystrophic changes, vacuolization in the molecular and granular layers, and aggregation of swollen Purkinje cells in group B animals compared with group C animals which showed only slight cellular dystrophy and inflammation. The mean cellular population was significantly ( ) higher in the treatment groups compared with the control. Conclusion. There was amelioration of damage of the cerebellum in the animals treated with neurovite and lamivudine combination compared to animals treated with only lamivudine. Therefore, there is need to give neurovite to patients on lamivudine therapy. 1. Introduction Lamivudine (INN)6 or 3TC is a levorotary pyrimidone-1,3-oxathiolane derivative and has the molecular formula C8H11N3O3S. Lamivudine is an effective and well-tolerated agent for treating chronic hepatitis B infection and acquired immunodeficiency syndrome [1, 2]. It is an antiretroviral drug in the therapeutic category of nucleoside reverse transcriptase inhibitor [2]. Lamivudine is very useful in preventing HIV and hepatitis B from multiplying by way of its active form, lamivudine triphosphate (3TCTP) which is generated via intracellular triple phosphorylation process. Lamivudine competitively inhibits viral transcriptase by causing termination of DNA replication, thus interrupting HIV replication [3]. Antiretroviral treatment can significantly prolong the lives of people living with HIV. Modern combination therapy is highly effective and people with HIV and on antiretroviral treatment could live for the rest of their lives without developing AIDS [4]. Despite these improvements, the prolonged use of highly active antiretroviral therapy (HAART) has led to certain neurologic complications such as myelopathy, neuropathy, neuropathic pain, and cognitive
References
[1]
P. D. Ziakas, P. Karsaliakos, and E. Mylonakis, “Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance,” Haematologica, vol. 94, no. 7, pp. 998–1005, 2009.
[2]
WHO, “Priotizing second-line antiretroviral drugs for adults and adolescents: a public health approach,” A Report of a WHO Working Group Meeting: World Health Organization, HIV Department, Geneva, Switzerland, pp. 1–44, 2007, http://www.who.int/hiv/pub/meetingreports/Second_Line_Antiretroviral.pdf.
[3]
GlaxoSmithkline, “Epivir？/Lamivudine. 3TC drug information online,” 2013, http://www.antimicrobe.org/drugpopup/Lamivudine.pdf.
[4]
Aidsmeds, “An almost normal life expectancy for people with HIV?” 2012, http://www.aidsmeds.com/articles/AM_Life_Expectancy_1667_23202.shtml.
[5]
G. J. Treisman and A. I. Kaplin, “Neurologic and psychiatric complications of antiretroviral agents,” AIDS, vol. 16, no. 9, pp. 1201–1215, 2002.
[6]
V. Tozzi, P. Balestra, R. Libertone, and A. Antinori, “Cognitive function in treated HIV patients,” Neurobehavioral HIV Medicine, vol. 2, pp. 95–113, 2010.
[7]
R. K. Heaton, T. D. Marcotte, M. Rivera Mindt et al., “The impact of HIV-associated neuropsychological impairment on everyday functioning,” Journal of the International Neuropsychological Society, vol. 10, no. 3, pp. 317–331, 2004.
[8]
A. Carr, A. Morey, P. Mallon, D. Williams, and D. R. Thorburn, “Fatal portal hypertension, liver failure, and mitochondrial dysfunction after HIV-1 nucleoside analogue-induced hepatitis and lactic acidaemia,” The Lancet, vol. 357, no. 9266, pp. 1412–1414, 2001.
[9]
K. Goodkin, M. A. Fletcher, and N. Cohen, “Clinical aspects of psychoneuroimmunology,” The Lancet, vol. 345, no. 8943, pp. 183–184, 1995.
[10]
J. Xu and T. Ikezu, “The comorbidity of HIV-associated neurocognitive disorders and alzheimer's disease: a foreseeable medical challenge in post-HAART era,” Journal of Neuroimmune Pharmacology, vol. 4, no. 2, pp. 200–212, 2009.
[11]
J. Schouten, P. Cinque, M. Gisslen, P. Reiss, and P. Portegies, “HIV-1 infection and cognitive impairment in the cART era: a review,” AIDS, vol. 25, no. 5, pp. 561–575, 2011.
[12]
D. D. Sewell, D. V. Jeste, J. H. Atkinson et al., “HIV-associated psychosis: a study of 20 cases,” American Journal of Psychiatry, vol. 151, no. 2, pp. 237–242, 1994.
[13]
E. Brooks, “Vitamin B12 Benefits,” 2010, http://ezinearticles.com/?Vitamin-B12-Benefits&id=5438902.
[14]
R. S. Beach, E. Mantero-Atienza, G. Shor-Posner et al., “Specific nutrient abnormalities in asymptomatic HIV-1 infection,” AIDS, vol. 6, no. 7, pp. 701–708, 1992.
[15]
J.-H. Gao, L. M. Parsons, J. M. Bower, J. Xiong, J. Li, and P. T. Fox, “Cerebellum implicated in sensory acquisition and discrimination rather than motor control,” Science, vol. 272, no. 5261, pp. 545–547, 1996.
[16]
J. A. Fiez, “Cerebellar contributions to cognition,” Neuron, vol. 16, no. 1, pp. 12–15, 1996.
[17]
V. Chizhikov and K. J. Millen, “Development and malformations of the cerebellum in mice,” Molecular Genetics and Metabolism, vol. 80, no. 1-2, pp. 54–65, 2003.
[18]
J. D. Schmahmann, “Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 16, no. 3, pp. 367–378, 2004.
[19]
J. H. Balsters, C. D. Whelan, I. H. Robertson, and N. Ramnani, “Cerebellum and cognition: evidence for the encoding of higher order rules,” Cerebral Cortex, vol. 23, pp. 1433–1443, 2012.
[20]
S. A. Lipton and H. E. Gendelman, “Dementia associated with the acquired immunodeficiency syndrome,” The New England Journal of Medicine, vol. 332, no. 14, pp. 934–940, 1995.
[21]
R. Ellis, D. Langford, and E. Masliah, “HIV and antiretroviral therapy in the brain: neuronal injury and repair,” Nature Reviews Neuroscience, vol. 8, no. 1, pp. 33–44, 2007.
[22]
E. O'Hearn and M. E. Molliver, “Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline,” Neuroscience, vol. 55, no. 2, pp. 303–310, 1993.
[23]
A. M. Tang, N. M. H. Graham, A. J. Kirby, L. D. McCall, W. C. Willett, and A. J. Saah, “Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV- 1)-infected homosexual men,” American Journal of Epidemiology, vol. 138, no. 11, pp. 937–951, 1993.
[24]
M. Tagliati, D. Simpson, S. Morgello, D. Clifford, R. L. Schwartz, and J. R. Berger, “Cerebellar degeneration associated with human immunodeficiency virus infection,” Neurology, vol. 50, no. 1, pp. 244–251, 1998.
[25]
L. Patrick, “Nutrients and HIV: part 2—vitamins A and E, zinc, B-vitamins, and magnesium,” Alternative Medicine Review, vol. 5, no. 1, pp. 39–51, 2000.
