The applications of nanotechnology to pharmacology are the potential appliance of biodegradable polymers and convection-enhanced drug delivery in the diagnostics and treatment of diseases. Chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades. The present study was to evaluate the possible effects of chitosan tripolyphosphate conjugated nanochloroquine against Plasmodium berghei infection on select makers of oxidative damage and antioxidant status in mitochondria of liver and spleen. P. berghei infection was developed in Swiss mice by intraperitoneal injection of 200？μL of infected blood. Parasite-infected mice were treated with chloroquine and nanoconjugated chloroquine. Superoxide radical generation, nitrate level, and oxidized glutathione were increased significantly ( ) in the mitochondria of infected group as compared to control group, and reduced glutathione level, activity of SOD, GPx, GR, and GST, and mitochondrial transmembrane potential were decreased significantly ( ), which were increased or decreased significantly ( ) near to normal in nanoconjugated chloroquine treated group than chloroquine treated group. So, the findings may suggest the advantageous role of nanoconjugated chloroquine against the P. berghei induced oxidative damage in hepatic and splenic mitochondria. 1. Introduction Despite years of effort, the developments of effective drug against malaria are available. To date, antimalarial drugs remain the major way to treat the disease. Presently, the most effective way of dealing with malaria is the administration of chemotherapeutic agents. Although drug treatments of malaria are currently the best means of disease management, there is an urgent need for the development of structurally novel and effective antimalarial drugs because of increasing resistance to most presently available antimalarial drugs [1–3]. The multiplication of the malaria parasite in the blood causes the pathology such as anemia, hemolysis, and damage of the essential organs of the host by the parasite products. Like other microbes, P. berghei is also a causative agent that should change the normal condition of host by utilizing or protecting defence factors. It is generally accepted that ROS, NO, and peroxynitrite kill intraerythrocytic malarial parasites [4, 5], but the parasite protect itself by antioxidant enzyme [6]. Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in malaria. After a short period of development and multiplication, these parasites
References
[1]
P. L. Olliaro and P. I. Trigg, “Status of antimalarial drugs under development,” Bulletin of the World Health Organization, vol. 73, no. 5, pp. 565–571, 1995.
[2]
W. Peters, “The problem of drug resistance in malaria,” Parasitology, vol. 90, pp. 705–715, 1985.
[3]
N. J. White, “Antimalarial drug resistance: the pace quickens,” Journal of Antimicrobial Chemotherapy, vol. 30, no. 5, pp. 571–585, 1992.
[4]
L. R. Brunet, “Nitric oxide in parasitic infections,” International Immunopharmacology, vol. 1, no. 8, pp. 1457–1467, 2001.
[5]
M. M. Stevenson and E. M. Riley, “Innate immunity to malaria,” Nature Reviews Immunology, vol. 4, no. 3, pp. 169–180, 2004.
[6]
A. Holmgren, “Antioxidant function of thioredoxin and glutaredoxin systems,” Antioxidants and Redox Signaling, vol. 2, no. 4, pp. 811–820, 2000.
[7]
P. Srivastava, S. K. Puri, G. P. Dutta, and V. C. Pandey, “Hepatic superoxide-scavenging system during Plasmodium berghei infection and chloroquine treatment,” Medical Science Research, vol. 19, no. 10, pp. 307–308, 1991.
[8]
C. Guinovart, M. M. Navia, M. Tanner, and P. L. Alonso, “Malaria: burden of disease,” Current Molecular Medicine, vol. 6, no. 2, pp. 137–140, 2006.
[9]
S. Dey, M. Guha, A. Alam et al., “Malarial infection develops mitochondrial pathology and mitochondrial oxidative stress to promote hepatocyte apoptosis,” Free Radical Biology and Medicine, vol. 46, no. 2, pp. 271–281, 2009.
[10]
I. Landau and P. Gautret, “Animal models: rodents,” in Malaria: Parasite Biology, Pathogenesis, and Protection, I. W. Sherman, Ed., pp. 401–417, ASM Press, Washington, DC, USA, 1998.
[11]
W. Peters, J. H. Portus, and B. L. Robinson, “The chemotherapy of rodent malaria, XXII. The value of drug resistant strains of P. berghei in screening for blood schizontocidal activity,” Annals of Tropical Medicine and Parasitology, vol. 69, no. 2, pp. 155–171, 1975.
[12]
E. C. Ibezim, C. T. Andrade, C. M. B. Barretto, D. C. Odimegwu, and F. F. D. Lima, “Ionically cross-linked chitosan/tripolyphosphate microparticles for the controlled delivery of pyrimethamine,” Ibinosina Journal of Medicine and Biological Sciences, vol. 3, no. 3, pp. 77–87, 2011.
[13]
J. W. Loh, M. Saunders, and L. Y. Lim, “Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells,” Toxicology and Applied Pharmacology, vol. 262, no. 3, pp. 273–282, 2012.
[14]
S. Tripathy, S. Das, S. P. Chakraborty, S. K. Sahu, P. Pramanik, and S. Roy, “Synthesis, characterization of chitosan-tripolyphosphate conjugated chloroquine nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: a dose and duration dependent approach,,” International Journal of Pharmaceutics, vol. 434, pp. 292–305, 2012.
[15]
S. Tripathy, S. P. Chakraborty, and S. Roy, “Superoxide radical generation mediated Plasmodium berghei infection in Swiss mice,” Al Ameen Journal of Medical Sciences, vol. 5, pp. 69–81, 2012.
[16]
J. R. Aprille and J. Austin, “Regulation of the mitochondrial adenine nucleotide pool size,” Archives of Biochemistry and Biophysics, vol. 212, no. 2, pp. 689–699, 1981.
[17]
A. Boveris, “Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria,” Methods in Enzymology, vol. 105, pp. 429–435, 1984.
[18]
S. KarMahapatra, S. P. Chakraborty, S. Das, and S. Roy, “Methanol extract of Ocimum gratissimum protects murine peritoneal macrophages from nicotine toxicity by decreasing free radical generation, lipid and protein damage and enhances antioxidant protection,” Oxidative Medicine and Cellular Longevity, vol. 2, no. 4, pp. 222–230, 2009.
[19]
O. H. Lowry, N. J. Rosenbrough, A. L. Farr, and R. J. Randall, “Protein measurement with the Folin phenol reagent,” The Journal of Biological Chemistry, vol. 193, no. 1, pp. 265–275, 1951.
[20]
P. Reungpatthanaphong and S. Mankhetkorn, “Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines,” Biological and Pharmaceutical Bulletin, vol. 25, no. 12, pp. 1555–1561, 2002.
[21]
B. R. Moore, J. D. Jago, and K. T. Batty, “Plasmodium berghei: parasite clearance after treatment with dihydroartemisinin in an asplenic murine malaria model,” Experimental Parasitology, vol. 118, no. 4, pp. 458–467, 2008.
[22]
R. Carter and D. Walliker, “New observations on the malaria parasites of rodents of the Central African Republic. Plasmodium vinckei petteri subsp. nov. and Plasmodium chabaudi Landau, 1965,” Annals of Tropical Medicine and Parasitology, vol. 69, no. 2, pp. 187–196, 1975.
[23]
B. S. Das and N. K. Nanda, “Evidence for erythrocyte lipid pepoxidation in acute falciparum malaria,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 93, no. 1, pp. 58–62, 1999.
[24]
J. H. Santos, B. S. Mandavilli, and B. Van Houten, “Measuring oxidative mtDNA damage and repair using quantitative PCR,” Methods in Molecular Biology, vol. 197, pp. 159–176, 2002.
[25]
N. Evelyne, P. Nathaline, F. Candau, et al., “Biopolymer and polymer nanoparticles and their biomedical applications,” Handbook of Nanostructure and Nanotechnology, vol. 5, pp. 577–635, 2000.
[26]
K. A. Janes, P. Calvo, and M. J. Alonso, “Polysaccharide colloidal particles as delivery systems for macromolecules,” Advanced Drug Delivery Reviews, vol. 47, no. 1, pp. 83–97, 2001.
[27]
H. Swai, B. Semete, L. Kalombo, and P. Chelule, “Potential of treating tuberculosis with a polymeric nano-drug delivery system,” Journal of Controlled Release, vol. 132, p. e48, 2008.
[28]
I. Landau and A. G. Chabaud, “Natural infection by 2 plasmodia of the rodent Thamnomys rutilans in the Central African Republic,” Comptes Rendus Hebdomadaires des Seances de l"Academie des Sciences D, vol. 261, no. 1, pp. 230–232, 1965.
[29]
M. Yoeli, B. Hargreaves, R. Carter, and D. Walliker, “Sudden increase in virulence in a strain of Plasmodium yoelii,” Annals of Tropical Medicine and Parasitology, vol. 69, no. 2, pp. 173–178, 1975.
[30]
B. S. Das and N. K. Nanda, “Evidence for erythrocyte lipid pepoxidation in acute falciparum malaria,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 93, no. 1, pp. 58–62, 1999.
[31]
A. Pabon, J. Carmona, L. C. Burgos, and S. Blair, “Oxidative stress in patients with non-complicated malaria,” Clinical Biochemistry, vol. 36, pp. 71–78, 2003.
[32]
M. J. Czaja, “Induction and regulation of hepatocyte apoptosis by oxidative stress,” Antioxidants and Redox Signaling, vol. 4, no. 5, pp. 759–767, 2002.
[33]
T. A. Sarafian and D. E. Bredesen, “Is apoptosis mediated by reactive oxygen species?” Free Radical Research, vol. 21, no. 1, pp. 1–8, 1994.
[34]
K. Biswas, U. Bandyopadhyay, I. Chattopadhyay, A. Varadaraj, E. Ali, and R. K. Banerjee, “A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical,” Journal of Biological Chemistry, vol. 278, no. 13, pp. 10993–11001, 2003.
[35]
D. R. Green and J. C. Reed, “Mitochondria and apoptosis,” Science, vol. 281, no. 5381, pp. 1309–1312, 1998.
[36]
H. U. Simon, A. Haj-Yehia, and F. Levi-Schaffer, “Role of reactive oxygen species (ROS) in apoptosis induction,” Apoptosis, vol. 5, no. 5, pp. 415–418, 2000.
[37]
M. Guha, S. Kumar, V. Choubey, P. Maity, and U. Bandyopadhyay, “Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway,” The FASEB Journal, vol. 20, no. 8, pp. E439–E449, 2006.
[38]
L. Sanchez-Torres, A. Rodriguez-Ropon, M. Aguilar-Medina, and L. Favila-Castillo, “Mouse splenic CD4+ and CD8+ T cells undergo extensive apoptosis during a Plasmodium chabaudi chabaudi AS infection,” Parasite Immunology, vol. 23, no. 12, pp. 617–626, 2001.
