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Antioxidant enzymes in Acanthocheilonema viteae and effect of antifilarial agents
S Batra1, R K Chatterjee, V M Srivastava
1Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
Abstract:
Adult worms of Acanthocheilonema viteae were found to be susceptible to the reactive oxygen intermediates (ROI) generated by the xanthine-xanthine oxidase (X-XO) system. The damage caused by this system was completely abolished by superoxide dismutase (SOD) and catalase but not by mannitol. The results, therefore, suggest that superoxide anions (O2-) and hydrogen peroxide (H2O2) alone or in combination might be toxic to the filariid. A. viteae exhibited the presence of an active enzyme system to protect itself against the oxidants. SOD and catalase were present in high levels of activities and appeared to constitute the major defence system. The role of glutathione peroxidase (GPx), on the other hand, seemed less important due to the weak activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH). A. viteae also released SOD, catalase and GPx in the ambient medium, which appear useful in protecting the filariid against ROI generated by the host in the immediate surroundings of the parasite. Antifilarial agents, diethylcarbamazine (DEC) and 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (82/437) appreciably inhibited catalase and GPx of A. viteae. Inhibition of these enzymes appears to render the parasite prone to H2O2 toxicity leading to death. No adverse effect on antioxidant enzymes of liver, lungs and subcutaneous tissue of Mastomys natalensis recorded as a result of exposure to 82/437 suggests a non-toxic nature to the compound.
Insights
Adult filarial worms Acanthocheilonema viteae are susceptible to reactive oxygen intermediates (ROI). Their antioxidant enzymes, superoxide dismutase and catalase, protect against these oxidants, but antifilarial agents can inhibit these defenses.
Area of Science:
- Parasitology
- Biochemistry
- Toxicology
Background:
- Filarial parasites like Acanthocheilonema viteae inhabit host environments rich in reactive oxygen intermediates (ROI).
- Understanding parasite defense mechanisms against host-generated oxidants is crucial for developing effective antifilarial therapies.
Purpose of the Study:
- To investigate the susceptibility of adult Acanthocheilonema viteae to reactive oxygen intermediates (ROI).
- To characterize the antioxidant enzyme systems of A. viteae and their role in parasite survival.
- To evaluate the impact of antifilarial agents on parasite antioxidant defenses.
Main Methods:
- Exposure of adult A. viteae to the xanthine-xanthine oxidase (X-XO) system generating ROI.
- Assessment of damage protection using superoxide dismutase (SOD), catalase, and mannitol.
- Enzyme activity assays for SOD, catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH).
- Investigation of antifilarial agents diethylcarbamazine (DEC) and compound 82/437 on parasite enzyme activities.
Main Results:
- A. viteae showed susceptibility to ROI, with damage mitigated by SOD and catalase, indicating toxicity from superoxide anions and hydrogen peroxide.
- The parasite possesses a robust antioxidant system, primarily driven by high activities of SOD and catalase.
- Extracellular release of SOD, catalase, and GPx by A. viteae suggests a role in combating host-derived ROI.
- Antifilarial agents DEC and 82/437 inhibited A. viteae catalase and GPx, potentially increasing susceptibility to hydrogen peroxide.
- Compound 82/437 showed no toxicity to host antioxidant enzymes in Mastomys natalensis.
Conclusions:
- Superoxide anions and hydrogen peroxide are toxic to A. viteae, but the parasite has effective antioxidant defenses.
- SOD and catalase are key components of the A. viteae antioxidant system, with GPx playing a lesser role.
- Antifilarial agents that inhibit these crucial enzymes may represent a viable strategy for treating filariasis.
- Compound 82/437 demonstrates potential as a safe and effective antifilarial agent due to its targeted action and lack of host toxicity.