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Published on: October 11, 2022
Selective modulation of antioxidant enzyme activities in host tissues during Rickettsia conorii infection
Elena Rydkina1, Sanjeev K Sahni, Lisa A Santucci
1Hematology-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.
Abstract:
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.
Insights
Oxidative stress plays a role in rickettsiosis pathogenesis. Antioxidant treatments like alpha-lipoic acid can protect against infection-induced injury by regulating antioxidant enzymes.
Area of Science:
- Pathogen-host interactions
- Oxidative stress mechanisms
- Antioxidant enzyme regulation
Background:
- Rickettsiosis, including Mediterranean spotted fever, is a significant public health concern.
- The precise mechanisms underlying rickettsiosis pathogenesis are not fully understood.
- Oxidative stress is implicated in various infectious diseases.
Purpose of the Study:
- To investigate the role of oxidative mechanisms in rickettsiosis.
- To examine the impact of Rickettsia conorii infection on antioxidant enzyme activities in vivo.
- To evaluate the protective effects of antioxidant treatment against rickettsiosis-induced oxidative injury.
Main Methods:
- Infection of C3H/HeN mice with Rickettsia conorii (sub-lethal and lethal doses).
- Microscopic examination of infected tissues (brain, lungs, testes) at 48 and 96 hours post-infection.
- Assay of antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, superoxide dismutase).
- Treatment with alpha-lipoic acid.
Main Results:
- Rickettsia conorii infection led to characteristic pathological changes and rickettsiae presence in endothelial cells.
- Viable R. conorii, but not inactivated forms, modulated antioxidant enzyme activities in a dose- and time-dependent manner.
- Significant changes in antioxidant enzyme activities were observed, particularly in the lungs.
- Alpha-lipoic acid treatment protected against oxidative injury and maintained reduced glutathione levels.
Conclusions:
- Oxidative mechanisms are involved in Rickettsia conorii pathogenesis.
- Regulatory enzymes of glutathione redox and superoxide scavenging systems are key in the host's antioxidant response.
- The extent of the antioxidant response varies with the rickettsial titer in different organs.
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