PMID- 38290256 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20240408 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 176 DP - 2024 Apr TI - Subchronic doses of artemether-lumefantrine, ciprofloxacin and diclofenac precipitated inflammatory and immunological dysfunctions in female Wistar rats. PG - 156515 LID - S1043-4666(24)00018-8 [pii] LID - 10.1016/j.cyto.2024.156515 [doi] AB - 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-1beta (Il-1beta), 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-1beta 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-alpha 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. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved. FAU - Oluwafunmilayo Ajayi, Juliana AU - Oluwafunmilayo Ajayi J AD - Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo state, Nigeria. Electronic address: joajayi33@pgschool.lautech.edu.ng. FAU - Bukoye Oyewo, Emmanuel AU - Bukoye Oyewo E AD - Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo state, Nigeria. Electronic address: eboyewo@lautech.edu.ng. FAU - Sanmi Adekunle, Adeniran AU - Sanmi Adekunle A AD - Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo state, Nigeria. Electronic address: asadekunle@lautech.edu.ng. FAU - Temidayo Ige, Peace AU - Temidayo Ige P AD - Bloomberg School of Public Health, John Hopkin University, Baltimore, MD, United States. FAU - Ayomide Akomolafe, Peter AU - Ayomide Akomolafe P AD - Department of Science Laboratory Technology, Federal Polytechnic, Ayede, Oyo state, Nigeria. LA - eng PT - Journal Article DEP - 20240129 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antimalarials) RN - 144O8QL0L1 (Diclofenac) RN - 0 (Artemether, Lumefantrine Drug Combination) RN - 5E8K9I0O4U (Ciprofloxacin) RN - 0 (Interleukin-6) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - C7D6T3H22J (Artemether) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Rats MH - Animals MH - Female MH - Rats, Wistar MH - *Antimalarials MH - Diclofenac/pharmacology MH - Artemether, Lumefantrine Drug Combination MH - Ciprofloxacin/pharmacology MH - Interleukin-6 MH - Vascular Cell Adhesion Molecule-1 MH - Artemether MH - Tumor Necrosis Factor-alpha OTO - NOTNLM OT - Artemether-lumefantrine OT - Ciprofloxacin OT - Diclofenac OT - Immunological dysfunctions OT - Inflammatory responses COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/31 00:42 MHDA- 2024/02/26 06:44 CRDT- 2024/01/30 18:06 PHST- 2023/11/21 00:00 [received] PHST- 2024/01/15 00:00 [revised] PHST- 2024/01/18 00:00 [accepted] PHST- 2024/02/26 06:44 [medline] PHST- 2024/01/31 00:42 [pubmed] PHST- 2024/01/30 18:06 [entrez] AID - S1043-4666(24)00018-8 [pii] AID - 10.1016/j.cyto.2024.156515 [doi] PST - ppublish SO - Cytokine. 2024 Apr;176:156515. doi: 10.1016/j.cyto.2024.156515. Epub 2024 Jan 29.