Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Exhibits Antioxidant
                    Mechanism for Abrogation of Cyclophosphamide-Induced Cardiac Damage and
                    Oxidative Hepatorenal Toxicity in Rats

Ademola C. Famurewa; Patrick M. Aja; John O. Medewase; Innocent Abi; Okoro C. Ogbonna; Casimir C. Ofor; Charles O. Nwonuma; Nnaemeka T Asogwa; Omotayo O. Erejuwa

doi:10.1055/a-1842-7596

Drug Research, Table of Contents

Drug Res (Stuttg) 2022; 72(07): 396-403
DOI: 10.1055/a-1842-7596

Original Article

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Exhibits Antioxidant Mechanism for Abrogation of Cyclophosphamide-Induced Cardiac Damage and Oxidative Hepatorenal Toxicity in Rats

Ademola C. Famurewa

¹Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria

,

Patrick M. Aja

²Department of Biochemistry, Faculty of Biological Sciences, Ebonyi State University, Abakaliki, Nigeria

,

John O. Medewase

³Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria

,

Innocent Abi

⁴Department of Physiology, Benue State University, Makurdi, Benue State, Nigeria

,

Okoro C. Ogbonna

⁵Department of Medical Biochemistry, School of Basic Medical Science, Federal University of Technology, Owerri, Imo State, Nigeria

,

Casimir C. Ofor

⁶Department of Pharmacology and Therapeutics, Faculty of Medicine, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria

,

Charles O. Nwonuma

⁷Department of Biochemistry, Landmark University, Omu-Aran, Kwara State, Nigeria

,

Nnaemeka T Asogwa

⁸Central Research and Diagnostic Laboratory, Tanke, Ilorin, Kwara State, Nigeria

,

Omotayo O. Erejuwa

⁹Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Medicine, College of Medical Sciences, Alex Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria

› Author Affiliations

Abstract

Cyclophosphamide (CYP) is a potent DNA-interactive anticancer drug; however, its clinical drawbacks are chiefly associated with induction of oxidative multi-organ toxicity. Sitagliptin (STG) is an antidiabetic dipeptidyl peptidase-4 inhibitor drug with antioxidant efficacy. Herein, we have explored whether STG could abrogate the CYP-induced oxidative stress-mediated cardiac and hepatorenal toxicities in male rats. Sitagliptin (20 mg/kg, o.p) was administered to rats for 5 consecutive days against organ toxicities induced by CYP (200 mg/kg, i.p) on day 5 only. CYP induced marked injuries in the liver, kidney and heart underscored by prominent increases in serum activities of ALT, AST, LDH, creatine kinase and levels of urea, uric acid and creatinine, while albumin level significantly decreased compared to normal control rats. Further, CYP considerably reduced the activities of SOD, CAT, GPx, and levels of GSH, whereas MDA level increased significantly in comparison to control rats. These biochemical alterations were confirmed by multiple histopathological lesions in the tissues. Interestingly, the STG pretreatment abrogated the biochemical and histopathological changes induced by CYP. These results provide first evidence that repurposing STG may protect the liver, kidney and heart from the oxidative deterioration associated with CYP chemotherapy.

Key words

Sitagliptin - chemotherapy - cyclophosphamide - oxidative stress - toxicity

Full Text

References

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