An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

Abstract

There is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stressinduced injuries that may contribute to disease progression. Pathogen invasion-and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete. In this review, we discuss the evidence for increased oxidative stress in chagasic disease, with emphasis on mitochondrial abnormalities, electron transport chain dysfunction and its role in sustaining oxidative stress in myocardium. We discuss the literature reporting the consequences of sustained oxidative stress in CCM pathogenesis.Key words: chagasic cardiomyopathy, reactive oxygen species, inflammation, mitochondria, oxidant/antioxidant status, oxidative damage. PARASITE, VECTOR AND TRANSMISSIONTrypanosoma cruzi, a parasitic protozoan of the ancient branch of eukaryotes (Kingdom Eukaryota, Order Kinetoplastida), is the etiological agent of Chagas disease in humans (Miles 2003). Currently, the World Health Organization estimates that 11-18 million individuals are infected worldwide (WHO 2002). Transmission of T. cruzi occurs predominantly via insect vectors of the subfamily Triatoma, family Reduviidae, referred to as " kissing bugs". Residing in the peridomestic habitat of mud-thatch Correspondence to: Nisha Garg Ph.D. E-mail: nigarg@utmb.edu houses in rural areas (Mott et al. 1978), Triatoma infestans in South America, Rhodnius prolixus in Venezuela, Colombia and Central America (Schofi eld and Dias 1999), and Triatoma barberi in Mexico (Guzman 2001), are the most common species responsible for transmission. Improvements in housing conditions and vector control measures instituted by the Southern Cone Initiative in 1991 have contributed to a decline in transmission in endemic countries (Schofi eld and Dias 1999). However, concern remains that reinfestation of homes by secondary sylvatic vectors, e.g. Triatoma sordida, will compromise the long-term effi cacy of vector control measures in Brazil and other Southern American countries (Monteiro et al. 2001, WHO 2002. Blood transfusion and organ transplantation represent further routes of T. cruzi transmission. Although many countries in Latin America screen blood donations for T. cruzi, infection rates ranging from 0.1% to 24.4% are estimated to occur through transfusion (WHO 2002).In the U.S., vector-transmitted human infections have been reported in the southern States (Ochs et al. 1996, Herwaldt et al. 2000. Several studies have shown the presence of the insect vector as well as infection of domestic dogs and wild animals in the US (Meurs et al. 1998, Bradley et al. 2000, Beard et al. 2003, Yabsley and Noblet 2002. Further, due to signifi cant increases in immigration to the USA and Canada from endemic countries and perinatal transmission, it is estimated that ∼ 100, 000 people residing...

Kinetics, subcellular localization, and contribution to parasite virulence of a Trypanosoma cruzi hybrid type A heme peroxidase ( Tc APx-CcP)

“…Recent studies have shown that T. cruzi lacking TcAPx is still capable of infecting cultured mammalian cells, albeit at a reduced level, and can still establish an infection in the mouse model of CD (20). Although the enzyme does not seem to be essential for parasite infectivity, its enhanced expression may represent an additional skill for the parasite to deal with host-derived oxidant toxicity both in the acute and chronic stages of the disease (6,21).…”

Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2 strain

“…Besides ROS, reactive nitrogen species (RNS), which are formed from the reaction of nitric oxide (NO) with superoxide radical 6,7 , may also lead to oxidative stress, responsible for many pathological conditions such as chagasic cardiomyopathy 8 .…”

Trypanosoma cruzi Induces the Reactive Oxygen Species-PARP-1-RelA Pathway for Up-regulation of Cytokine Expression in Cardiomyocytes

“…During the chronic phase, diffused inflammatory infiltrate persists in the myocardium (reviewed in Refs. 5,6). Besides infiltration of inflammatory infiltrate, cardiomyocytes are also reported to produce cytokines in response to T. cruzi infection (7), although the signaling events are not known.…”