Multisystem Effects of Repeated Co-codamol Exposure in Male Wistar Rats: Haematological, Biochemical, Oxidative, Inflammatory, Histopathological and Molecular-docking Evidence
Abiodun Bukunmi Aborisade *
Department of Medical Biochemistry, Faculty of Basic Medical Sciences, Osun State University, Osogbo, Osun State, Nigeria.
Olaleye Samuel Aremu
Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Osun State University, Osogbo, Osun State, Nigeria.
Adewale Adetutu
Department of Biochemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Co-codamol combines paracetamol (acetaminophen) and codeine, but the multisystem effects of repeated exposure to the combined formulation remain insufficiently characterised. This study evaluated the effects of repeated oral co-codamol administration on haematological, hepatic, renal, oxidative, inflammatory and histopathological parameters in adult male Wistar rats and examined predicted interactions of selected constituents with analgesia-associated molecular targets. Twenty rats were randomly allocated to four groups (n = 5). Groups A, B and C received co-codamol at 100, 97 and 90 mg/kg body weight, respectively, while Group D received normal saline. Treatments were administered orally once daily for 28 consecutive days. Repeated co-codamol exposure was associated with alterations in erythrocyte, leucocyte, platelet and red-cell indices. Changes were also observed in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and alkaline phosphatase activities, together with serum creatinine and urea concentrations. Hepatic and renal malondialdehyde, reduced glutathione, superoxide dismutase and total protein were assessed, with treatment-associated alterations observed in several of these parameters. Hepatic and renal IL-6 and IL-10 concentrations were also altered. Histopathological examination demonstrated treatment-associated changes in liver and kidney tissues. Molecular docking showed favourable predicted interactions between codeine and selected analgesia-associated targets. The measured responses were not uniformly proportional to dose across all endpoints. Overall, repeated co-codamol exposure was associated with multisystem biological alterations under the experimental conditions, while the docking findings provide computational hypotheses that require experimental validation.
Keywords: Co-codamol, paracetamol, codeine, oxidative stress, hepatotoxicity, renal function, Wistar rats