Vol. 6 No. 1 (2026): PTNM 2026 First Issue
Adejuwon A Adeneye, Kehinde S Fashikun, Nadrah G Akinlade, Abdulfatai O Ojewale, Ikechuckwu I Okoye
Background and Purpose: Doxorubicin (DOX), a widely used chemotherapeutic agent, is associated with severe off target hepatorenal toxicity due to oxidative stress, inflammation and apoptosis. This study investigated the possible protective effects of 50-200 mg/kg/day pretreatment of a fixed-dose combination of diosmin-hesperidin (DH) against DOX-induced hepatorenal toxicity in male Wistar rats.
Methods: Forty-eight (48) young adult male Wistar rats were randomly allotted to 8 treatment groups of 6 rats per group and orally pretreated with DH at doses of 50, 100, and 200 mg/kg/day as well as 20 mg/kg/day silymarin (SIL), before DOX administration (3 mg/kg/i.p. route on alternate days), all for 10 days. Hepatic and renal function tests, oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reduced glutathione (GSH)], inflammatory markers [tumor necrosis factor-alpha (TNF-?) and interleukin-10 (IL-10)], and histopathological assessments were the measuring endpoints.
Results: Biochemical analysis revealed that repeated treatment with DOX significantly (P<0.05, P<0.001, and P<0.0001) impaired hepatic and renal function, increased oxidative stress (elevated MDA, reduced SOD, CAT, and GSH), and promoted inflammation (elevated TNF-? and reduced IL-10). Histopathological analysis revealed severe hepatic and tubulo-glomerular degenerative changes. DH pretreatment effectively mitigated DOX-induced toxicity by improving hepatic and renal function, restoring oxidative balance, reducing inflammation, and preserving tissue architecture in a dose-dependent manner. The highest dose (200 mg/kg) provided the most significant hepatoprotective and renoprotective effects.
Conclusion: These findings suggest that DH exerts protective effects against DOX-induced hepatorenal toxicity through its antioxidant and anti-inflammatory properties. This study highlights the therapeutic potential of DH as an adjunct in chemotherapy-induced organ toxicity.
Adejuwon A Adeneye — Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja, Lagos State, Nigeria.
Kehinde S Fashikun — Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja, Lagos State, Nigeria.
Nadrah G Akinlade — Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja, Lagos State, Nigeria..
Abdulfatai O Ojewale — Department of Anatomy, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja, Lagos State, Nigeria.
Ikechuckwu I Okoye — Department of Pathology and Oral Medicine, Faculty of Dentistry, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja, Lagos State, Nigeria.