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

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

doi:10.1007/s12639-022-01553-8

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

J Parasit Dis. 2023 Mar;47(1):167-184. doi: 10.1007/s12639-022-01553-8. Epub 2022 Dec 1.

Authors

Lynn Kitwan¹, Celestine Makobe¹, Raymond Mdachi², Dawn Nyawira Maranga³, Alfred Orina Isaac⁴, James Nyabuga Nyariki⁵

Affiliations

¹ Department of Medical Microbiology Department, Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya.
² Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, Kikuyu, Kenya.
³ Animal Science Department, Institute of Primate Research, Nairobi, 00502 Kenya.
⁴ Department of Pharmaceutical Sciences and Technology, Technical University of Kenya, Nairobi, Kenya.
⁵ Department of Biochemistry and Biotechnology, Technical University of Kenya, Nairobi, Kenya.

Abstract

During the late stage of Human African Trypanosomiasis (HAT), there is severe cytokine-driven inflammation, oxidative stress and organ damage. Controlling inflammation and oxidative damage presents unique therapeutic opportunities to improve treatment outcome. The current study sought to determine the putative impact of Coenzyme-Q10 (Co-Q₁₀), a potent antioxidant and anti-inflammatory, on adverse inflammatory and oxidative events during Trypanosoma brucei rhodesiense (T.b.r) infection. Group one constituted the control; the second group was infected with T.b.r; the third group was orally administered with 200 mg/kg Co-Q₁₀ for two weeks; thereafter, Co-Q₁₀ administration continued after infection with T.b.r. Co-Q₁₀ improved the survival rate of infected mice and prevented full blown parasite driven splenomegaly and hepatomegaly. Co-Q₁₀ prevented characteristic T.b.r-driven breach of the blood brain barrier and improved neurological integrity among T.b.r infected mice. Co-Q₁₀ protected from T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia. T.b.r-induced oxidative stress in the vital organs was assuaged following exposure to Co-Q₁₀. Co-Q₁₀ blocked T.b.r-induced derangement of high density lipoprotein and triglyceride levels. Co-Q₁₀ significantly abrogated T.b.r-driven elevation of serum TNF-α and IFN-γ levels. Moreover, T.b.r-induced kidney and liver damage was assuaged by Co-Q₁₀ administration. Co-Q₁₀ administration downregulated T.b.r-induced elevation of uric acid and C-reactive protein. Likewise, T.b.r infected mice receiving Co-Q₁₀ exhibited normal brain architecture. In conclusion, treatment with Co-Q₁₀ may be useful in protecting against T.b.r-mediated organ injury, lethal inflammation and oxidative stress commonly present in severe late stage HAT; and presents unique opportunities for an adjunct therapy for late stage HAT.

Keywords: Blood brain barrier; Coenzyme-Q10; Inflammation; Oxidative stress; Trypanosoma brucei rhodesiense.

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