Hydroxychloroquine and zinc ameliorate interleukin-6 associated hepato-renal toxicity induced by Aspergillus fumigatus in experimental rat models

*Okoye, J. O., Basil, A. T., Okoli, O. G., Achebe, P. O., Obi, C. M., and Ekekwe, N. E.
Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, Nnamdi Azikiwe University, Nnewi Campus, Nigeria

*Correspondence to: jog.okoye@unizik.edu.ng; +2347031119994; ORCID: 0000-0002-7194-5592

Abstract:
Background: In Nigeria, immunocompromised persons, particularly those living with HIV, are at an increased risk of developing invasive pulmonary aspergillosis caused by Aspergillus fumigatus. Interestingly, this condition produces symptoms that can be easily mistaken for those of COVID-19. This misdiagnosis results in their treatment with zinc and hydroxychloroquine (HCQ). To better understand the pathophysiology of aspergillosis and determine the therapeutic and toxic effects of zinc and HCQ, this study examined liver and renal functions in experimental rat models.

Methodology: Twenty-eight Albino rats, randomised into 7 groups (n=4 each) designated A to G, were used for this study. Group A rats received standardized rat chow and distilled water only. Group B rats received moderate dose of HCQ only. Group C to G rats received immunosuppressive agents (an alkylating agent: cyclo- phosphamide and a steroid: hydrocortisone) to simulate an immunocompromised state before being infected with A. fumigatus suspension (AFS). Group C rats received AFS without treatment. Group D rats simultaneously received AFS and low dose of HCQ. Group E rats simultaneously received AFS and moderate dose of HCQ. Group F rats simultaneously received AFS and high dose of HCQ, and Group G rats simultaneously received AFS and moderate dose of HCQ and zinc. Serum levels of interleukin (IL)-6 and IL-10, liver enzymes, and renal parameters were measured using standard methods. The weights of the lungs, liver, and kidneys of each rat were measured after being sacrificed. One-way analysis of variance (ANOVA) was used to compare the means (±SD) of the biochemical variables and relative weight of the organs, while Post Hoc test was used for group comparison. Pearson’s correlation was used to determine relationship between parameters, with significant levels established at p<0.05.

Results: Higher levels of serum alanine transaminase, creatinine, and urea and lower relative lung weight were observed in group C rats (infected but untreated) compared to rats in other groups (p<0.001). Higher IL-6 levels and IL-6/IL-10 ratio were also observed in group C rats compared to rats in other groups (p>0.05).

Conclusion: This study revealed that HCQ and zinc ameliorate oxidative stress and hepato-renal damage induced by A. fumigatus in Albino rats.

Keywords: Cytokine, Oxidative stress, Aspergillosis, Interleukin-6, Interleukin-10

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Hydroxychloroquine and zinc ameliorate interleukin-6 associated hepato-renal toxicity induced by Aspergillus fumigatus in experimental rat models