Subchronic doses of artemether-lumefantrine, ciprofloxacin and diclofenac precipitated inflammatory and immunological dysfunctions in female Wistar rats

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Recents reports have shown increases in the abuse of anti-malaria, antibiotic and analgesic drugs. This study evaluated the effects of co-administration of artemether-lumefantrine (AL), ciprofloxacin (CPX) and diclofenac (DFC) on inflammatory and immunological status of female Wistar rats. Ninety-six female Wistar rats were assigned into eight groups of twelve animals each. Group A was control, groups B, C, D, E, F, G and H were administered AL, CPX, DFC, AL + CPX, AL + DFC, CPX + DFC and AL + CPX + DFC respectively. Dosages of administered drugs were 178 mg/kg b/w of AL, 185 mg/kg b/w of CPX and 9 mg/kg b/w of DFC. Animals were sacrificed after 6 and 12 weeks of oral administration. Blood was obtained through cardiac puncture. The liver was harvested and processed for immunohistochemical analysis. Differential leukocyte count and neutrophil adhesion test was conducted on whole blood. Immunological response was assessed by the serum levels of C-reactive protein (CRP), interleukin-1β (Il-1β), interleukin-6 (Il-6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, and total immunoglobulin G. Data were analyzed with Graph pad prism 5, using one way analysis of variance at 5 % level of significance. Total leukocyte, lymphocyte and basophils count increased (p<0.05) in B, C, E, F, G and H, while neutrophil count decreased (p<0.05) in D, E, G and H at 6 weeks. Neutrophil adhesion decreased (p<0.05) in B, E, F, G and H at 6 weeks. There was no significant difference (p>0.05) in the expression of Il-6, MCP-1 and VCAM-1 across the groups. Il-1β decreased in H, while CRP increased in H at 6 weeks and 12 weeks. MPO activity decreased (p<0.05) in B, C, D, E, G and H at 6 weeks, but increased (p<0.05) in D and G at 12 weeks. Immunohistochemical analysis indicated increase (p<0.05) in tumour necrosis factor-α in liver tissues of B, C, D, E, F and G, while nuclear factor erythroid 2-related factor 2 increased (p<0.05) in C, D, E, F and G, but decreased (p<0.05) in H at 12 weeks. The co-administration of AL, CPX and DFC induced inflammatory responses with attendant immunological dysfunctions and liver damage.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:176

Enthalten in:

Cytokine - 176(2024) vom: 01. Apr., Seite 156515

Sprache:

Englisch

Beteiligte Personen:

Oluwafunmilayo Ajayi, Juliana [VerfasserIn]
Bukoye Oyewo, Emmanuel [VerfasserIn]
Sanmi Adekunle, Adeniran [VerfasserIn]
Temidayo Ige, Peace [VerfasserIn]
Ayomide Akomolafe, Peter [VerfasserIn]

Links:

Volltext

Themen:

144O8QL0L1
5E8K9I0O4U
Antimalarials
Artemether
Artemether, Lumefantrine Drug Combination
Artemether-lumefantrine
C7D6T3H22J
Ciprofloxacin
Diclofenac
Immunological dysfunctions
Inflammatory responses
Interleukin-6
Journal Article
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1

Anmerkungen:

Date Completed 26.02.2024

Date Revised 08.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.cyto.2024.156515

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367805812