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

1   Department 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
2   Department of Biochemistry, Faculty of Biological Sciences, Ebonyi State University, Abakaliki, Nigeria
,
John O. Medewase
3   Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
,
Innocent Abi
4   Department of Physiology, Benue State University, Makurdi, Benue State, Nigeria
,
Okoro C. Ogbonna
5   Department of Medical Biochemistry, School of Basic Medical Science, Federal University of Technology, Owerri, Imo State, Nigeria
,
Casimir C. Ofor
6   Department of Pharmacology and Therapeutics, Faculty of Medicine, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Charles O. Nwonuma
7   Department of Biochemistry, Landmark University, Omu-Aran, Kwara State, Nigeria
,
Nnaemeka T Asogwa
8   Central Research and Diagnostic Laboratory, Tanke, Ilorin, Kwara State, Nigeria
,
Omotayo O. Erejuwa
9   Department 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
Funding Self-funded work

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.



Publication History

Received: 04 April 2022

Accepted: 02 May 2022

Article published online:
30 June 2022

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