Coenzyme Q10 prevented Trypanosoma brucei rhodesiense-mediated breach of the blood brain barrier, inflammation and organ damage in late stage of Human African Trypanosomiasis

Kitwan, Lynn; Makobe, Celestine; Mdachi, Raymond; Maranga, Dawn Nyawira; Isaac, Alfred; Nyariki, James Nyabuga

doi:10.1007/s12639-022-01553-8

Cited by 4 publications

(2 citation statements)

References 65 publications

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“…Indeed, HAT due to Trypanosoma brucei rhodesiense has been observed to provoke multiorgan failure manifested by liver, spleen, and cardiac failure-associated pathologies during the frst stage and detrimental neuropathological features in the central nervous system are observed during the second severe stage of the disease [28,29]. Drug treatment for the severe late stage of HAT relies on intravenous melarsoprol, though very efective the drug is very toxic and painful to administer and is associated with severe post-treatment reactive encephalopathy (PTRE) which develops in 10% of the patients with about half of the fatality cases witnessed [30].…”

Section: Introductionmentioning

confidence: 99%

Coinfection with Schistosoma mansoni Enhances Disease Severity in Human African Trypanosomiasis

Mitalo,

Waiganjo,

Mokua Mose

et al. 2023

Journal of Tropical Medicine

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Introduction. Human African trypanosomiasis (HAT) and schistosomiasis are neglected parasitic diseases found in the African continent. This study was conducted to determine how primary infection with Schistosoma mansoni affects HAT disease progression with a secondary infection with Trypanosoma brucei rhodesiense (T.b.r) in a mouse model. Methods. Female BALB-c mice (6–8 weeks old) were randomly divided into four groups of 12 mice each. The different groups were infected with Schistosoma mansoni (100 cercariae) and Trypanosoma brucei rhodesiense (5.0 × 104) separately or together. Twenty-one days after infection with T.b.r, mice were sacrificed and samples were collected for analysis. Results. The primary infection with S. mansoni significantly enhanced successive infection by the T.b.r; consequently, promoting HAT disease severity and curtailing host survival time. T.b.r-induced impairment of the neurological integrity and breach of the blood-brain barrier were markedly pronounced on coinfection with S. mansoni. Coinfection with S. mansoni and T.b.r resulted in microcytic hypochromic anemia characterized by the suppression of RBCs, hematocrit, hemoglobin, and red cell indices. Moreover, coinfection of the mice with the two parasites resulted in leukocytosis which was accompanied by the elevation of basophils, neutrophils, lymphocytes, monocytes, and eosinophils. More importantly, coinfection resulted in a significant elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, creatinine, urea, and uric acid, which are the markers of liver and kidney damage. Meanwhile, S. mansoni-driven dyslipidemia was significantly enhanced by the coinfection of mice with T.b.r. Moreover, coinfection with S. mansoni and T.b.r led to a strong immune response characterized by a significant increase in serum TNF-α and IFN-γ. T.b.r infection enhanced S. mansoni-induced depletion of cellular-reduced glutathione (GSH) in the brain and liver tissues, indicative of lethal oxidative damage. Similarly, coinfection resulted in a significant rise in nitric oxide (NO) and malondialdehyde (MDA) levels. Conclusion. Primary infection with S. mansoni exacerbates disease severity of secondary infection with T.b.r in a mouse model that is associated with harmful inflammatory response, oxidative stress, and organ injury.

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Section: Introductionmentioning

confidence: 99%

Coinfection with Schistosoma mansoni Enhances Disease Severity in Human African Trypanosomiasis

Mitalo,

Waiganjo,

Mokua Mose

et al. 2023

Journal of Tropical Medicine

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“…Moreover, considering the significant inflammatory responses associated with PTRE and antioxidant system failure due to melarsoprol treatment, it is logical to use compounds, which have anti-inflammatory and antioxidant properties in HAT management. Previous studies have given beneficial results when compounds with potent antioxidant and anti-inflammatory properties are used alongside melarsoprol like CoQ10 and anthocyanins [ 6 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Ginkgo biloba attenuated detrimental inflammatory and oxidative events due to Trypanosoma brucei rhodesiense in mice treated with melarsoprol

Wendo,

Mbaria,

Nyariki

et al. 2024

PLoS Negl Trop Dis

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Background The severe late stage Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei rhodesiense (T.b.r) is characterized by damage to the blood brain barrier, severe brain inflammation, oxidative stress and organ damage. Melarsoprol (MelB) is currently the only treatment available for this disease. MelB use is limited by its lethal neurotoxicity due to post-treatment reactive encephalopathy. This study sought to assess the potential of Ginkgo biloba (GB), a potent anti-inflammatory and antioxidant, to protect the integrity of the blood brain barrier and ameliorate detrimental inflammatory and oxidative events due to T.b.r in mice treated with MelB. Methodology Group one constituted the control; group two was infected with T.b.r; group three was infected with T.b.r and treated with 2.2 mg/kg melarsoprol for 10 days; group four was infected with T.b.r and administered with GB 80 mg/kg for 30 days; group five was given GB 80mg/kg for two weeks before infection with T.b.r, and continued thereafter and group six was infected with T.b.r, administered with GB and treated with MelB. Results Co-administration of MelB and GB improved the survival rate of infected mice. When administered separately, MelB and GB protected the integrity of the blood brain barrier and improved neurological function in infected mice. Furthermore, the administration of MelB and GB prevented T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia, as well as T.b.r-driven downregulation of total WBCs. Glutathione analysis showed that co-administration of MelB and GB prevented T.b.r-induced oxidative stress in the brain, spleen, heart and lungs. Notably, GB averted peroxidation and oxidant damage by ameliorating T.b.r and MelB-driven elevation of malondialdehyde (MDA) in the brain, kidney and liver. In fact, the co-administered group for the liver, registered the lowest MDA levels for infected mice. T.b.r-driven elevation of serum TNF-α, IFN-γ, uric acid and urea was abrogated by MelB and GB. Co-administration of MelB and GB was most effective in stabilizing TNFα levels. GB attenuated T.b.r and MelB-driven up-regulation of nitrite. Conclusion Utilization of GB as an adjuvant therapy may ameliorate detrimental effects caused by T.b.r infection and MelB toxicity during late stage HAT.

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Manipulative neuroparasites: uncovering the intricacies of neurological host control

Gowda,

Dinesh,

Sharma

2023

Arch Microbiol

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Coenzyme Q10 prevented Trypanosoma brucei rhodesiense-mediated breach of the blood brain barrier, inflammation and organ damage in late stage of Human African Trypanosomiasis

Cited by 4 publications

References 65 publications

Coinfection with Schistosoma mansoni Enhances Disease Severity in Human African Trypanosomiasis

Coinfection with Schistosoma mansoni Enhances Disease Severity in Human African Trypanosomiasis

Ginkgo biloba attenuated detrimental inflammatory and oxidative events due to Trypanosoma brucei rhodesiense in mice treated with melarsoprol

Manipulative neuroparasites: uncovering the intricacies of neurological host control

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