Selective modulation of antioxidant enzyme activities in host tissues during Rickettsia conorii infection.
The involvement of oxidative mechanisms in the pathogenesis of rickettsiosis was investigated using infection of C3H/HeN mice with sub-lethal and lethal infectious doses of Rickettsia conorii, the causative agent of Mediterranean spotted fever. Microscopic examination of tissues at 48 and 96 h post-infection revealed characteristic pathologic features and the presence of rickettsiae in the endothelium of infected tissues. Activities of key antioxidant enzymes, namely glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and superoxide dismutase, at these times exhibited a pattern of differential and selective modulation in brain, lungs, and testes of mice infected with viable organisms, whereas heat-inactivated or sonically disrupted rickettsiae had no effect. Of these, most significant changes were evident in the lungs of infected animals. Adaptive alterations in oxidant-scavenging enzymes occurred in apparent correlation with the dose and duration of infection. Treatment with an antioxidant, alpha-lipoic acid, protected against infection-induced oxidative injury via regulation of antioxidant enzyme activities and maintenance of reduced glutathione levels. These results suggest the involvement of regulatory enzymes of glutathione redox and superoxide scavenging systems in the antioxidant response during in vivo infection, the extent of which varies with the titer of viable rickettsiae in different organs of the host.
Rydkina
Elena
E
Hematology-Oncology Unit, Hemostasis and Thrombosis Program, Department of Medicine, University of Rochester School of Medicine and Dentistry, Box 610, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Sahni
Sanjeev K
SK
Santucci
Lisa A
LA
Turpin
Loel C
LC
Baggs
Raymond B
RB
Silverman
David J
DJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001907:Boutonneuse Fever / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004727:Endothelium / Q000382:microbiology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D020114:Rickettsia conorii / Q000472:pathogenicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D008063:Thioctic Acid; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione