Sinapic Acid Ameliorates Oxidative Stress, Inflammation, and Apoptosis in Acute Doxorubicin-Induced Cardiotoxicity via the NF-κB-Mediated Pathway.

Abstract

In the present study, we explored SA's activity against DOX-induced cardiotoxicity and revealed its underlying mechanisms. Male Wistar rats (weight, 190-210g; n = 6) were randomly divided into four groups: group I, normal control; group II, DOX 15 mg/kg via intraperitoneal (ip) route; group III, administered DOX+SA 20 mg/kg; and group IV, administered DOX+captopril (CAP 30 mg/kg). SA and CAP were administered orally for seven days, and DOX (15 mg/kg) was injected intraperitoneally an hour before SA treatment on the fifth day. Forty-eight hours after DOX administration, animals were anesthetized and sacrificed for molecular and histology experiments. SA significantly mitigated the myocardial effects of DOX, and following daily administration, it reduced serum levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB to near normal values. Levels of oxidative stress markers, glutathione-peroxidase, superoxide dismutase, and catalase, in the cardiac tissue were significantly increased, whereas malondialdehyde levels decreased after SA treatment in DOX-administered rats. Furthermore, DOX caused an inflammatory reaction by elevating the levels of proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and endothelin- (ET-) 1, as well as nuclear factor kappa-B (NF-κB) expression. Daily administration of SA significantly repressed TNF-α, IL-1β, ET-1, and NF-κB levels. caspase-3 and Bax expression, bcl-2-like protein and caspase-3 activities and levels. Overall, we found that SA could inhibit DOX-induced cardiotoxicity by inhibiting oxidative stress, inflammation, and apoptotic damage.

• Authors: Yousef A Bin Jardan, Mushtaq Ahmad Ansari, Mohammad Raish, Khalid M Alkharfy, Abdul Ahad, Fahad I Al-Jenoobi, Nazrul Haq, Mohd Rashid Khan, Ajaz Ahmad
• Journal: BioMed research international (Biomed Res Int) Vol. 2020 Pg. 3921796 ( 2020) ISSN: 2314-6141 [Electronic] United States
• PMID: 32258120 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Yousef A. Bin Jardan et al.

Chemical References

• Coumaric Acids
• NF-kappa B
• sinapinic acid
• Doxorubicin

Topics

• Animals
• Apoptosis (drug effects)
• Cardiotoxicity (drug therapy, etiology, genetics, pathology)
• Coumaric Acids (pharmacology)
• Disease Models, Animal
• Doxorubicin (adverse effects)
• Humans
• Inflammation (chemically induced, drug therapy, genetics, pathology)
• NF-kappa B (genetics)
• Neoplasms (complications, drug therapy, genetics)
• Oxidative Stress (drug effects)
• Rats