Cardioprotective Effect of Quercetin and Sitagliptin in Doxorubicin-Induced Cardiac Toxicity in Rats

Abstract

Objective: A previous study revealed a pronounced protective effect of combining quercetin (QC) with sitagliptin (STN) in testicular tissue. Accordingly, this study was designed to evaluate the cardioprotective effects of QC and STN each alone or in combination in doxorubicin (DOX)-induced cardiotoxicity in the rats. Methodology: Thirty male adult Wistar rats were divided into five groups: the first group (control) treated with sodium chloride, the second group treated with DOX (3 mg/kg I. P. injection), the third group treated with DOX with a combination of QC (80 mg/kg), and STN (10 mg/kg), the fourth group treated with DOX and QC and the fifth group treated with DOX and STN. Blood was collected on day 22 and used for assessment of serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, C-reactive protein (CRP), and total antioxidant capacity (TAOC). Atherogenic indices were also calculated. Cardiac tissue was sent for histopathological analysis. Results: DOX produced a significant increase in the level of troponin, LDH, CKP, CRP, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), and atherogenic index of plasma; and significantly decreased TAOC. The combination of quercetin and sitagliptin was more effective than each treatment alone in restoring the level of troponin, LDH, CKP, CRP, Cholesterol, LDL, TG, atherogenic index of plasma and significantly increased TAOC compared to DOX treated group. The histopathological finding also supports the biochemical results. Conclusion: The study revealed the cardioprotective effects of the combination of QC and STN which could be attributed to the additive effects of this combination through antioxidant, anti-inflammatory, lipid lowering and anti-atherogenic activities; suggesting it as a good therapeutic candidate to be tested in the clinical setting.

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis

“…In addition, it was reported that treatments exhibiting antihyperlipidemic effects can decrease DXB-induced cardiotoxicity [ 26 , 27 ]. The administration of DXB was associated with significant increases in serum TG, TC and LDL-C, while HDL was markedly reduced, corroborating the findings of previous studies [ 24 , 25 ]. COST significantly ameliorated DOX-induced hyperlipidemia in the treated rats.…”

“…Several studies have shown the prominent role of lipids in cardiovascular diseases and the role of DXB-induced hyperlipidemia has been well documented [ 24 , 25 ]. DXB interferes with the metabolism and synthesis of lipids resulting in high serum and cardiac lipid profiles [ 9 , 16 ].…”

Cardioprotective effects of alpha‐mangostin on doxorubicin‐induced cardiotoxicity in rats

“…DOX administration significantly elevated LDH and CK‐MB contents compared to the saline group, which has been reported in many investigations (Aygün & Gul, 2019; Momin et al, 2012; Ozdoğan et al, 2011; Yagmurca et al, 2003). Furthermore, it was shown that administration of DOX (3 mg/kg for 6 injections in 2 weeks, intraperitoneally) elevated the serum level of LDH in rats (Aziz, 2021). It has been suggested that DOX by decreasing oxygen or glucose supply can damage the membrane of the myocardial cell and result in leakage of cellular enzymes to blood flow (Momin et al, 2012).…”

Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis

“…However, Dox induces apoptosis by generating high levels of ROS in tumor cells leading to lipid peroxidation, DNA damage, and the trigger of apoptosis [28]. Beside the apoptotic effect of STG, several studies reported its impact in halting some of the Dox-induced multiple organ toxicity including cardiotoxicity [53][54][55] and nephrotoxicity [56].…”