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.

Gastroprotective Effect of Sinapic Acid on Ethanol-Induced Gastric Ulcers in Rats: Involvement of Nrf2/HO-1 and NF-κB Signaling and Antiapoptotic Role

“…SA has potent anti-lipid peroxidation and free radical scavenging activities ( Chen, 2016 ). These results are consistent with those of previous reports ( Chen, 2016 ; Raish et al, 2018a ; Raish et al, 2018b ; Raish et al, 2019 ; Bin Jardan et al, 2020 ), in that gastric mucosal apoptotic injuries have been shown to by prompted by oxidative stress and inflammatory cytokines via the intrinsic mitochondrial pathway. The oxidative-stress-induced apoptosis controlled by the antiapoptotic Bcl2 and pro-apoptotic Bax and caspase-3 proteins plays a significant role in the disruption of gastric mucosal wall integrity after ethanol intubation ( Durkin et al, 2006 ; Liu et al, 2018 ; He et al, 2019 ).…”

“…We found that the dose response in terms of GUI and PGE2 levels for the three dose levels of SA, 40 mg/kg had the maximum gastroprotective effect. This was further corroborated by our previous research, which indicated that 40 mg/kg of SA has maximum antioxidant, anti-inflammatory, and antiapoptotic activity ( Raish et al, 2018a ; Raish et al, 2019 ; Bin Jardan et al, 2020 ). Several reports have implicated alcohol in gastric mucosal damage and upper gastrointestinal bleeding ( Teyssen and Singer, 2003 ; Simoes et al, 2019 ).…”

“…Polyphenols possess several biological activities, including antioxidant and gastroprotective activities ( Mota et al, 2009 ; Sumbul et al, 2011 ). SA (3,5-dimethoxy-4-hydroxycinnamic acid) is an orally bioavailable phytoconstituent that is present in cereals, fruits, oil, and vegetables and has potent antioxidant, antidiabetic, anticancer, anti-inflammatory, chemopreventive, and antiapoptotic activities ( Chen, 2016 ; Raish et al, 2018a ; Bin Jardan et al, 2020 ). No in vivo studies have examined the gastroprotective effect of SA, or the mechanism underlying the gastric protection afforded by it in the GUs of ethanol-induced rats.…”

“…SA is a nutraceutical that has exhibited cytoprotective, antioxidant, and anti-inflammatory activity in several studies in various in vivo models over 1 week or 10 days; therefore, a span of 7 days was selected here ( Raish et al, 2019 ; Bin Jardan et al, 2020 ). A pilot study was conducted to assess the most appropriate dose of SA, and the data showed that 40 mg/kg had the maximum gastroprotective effect.…”

“…Natural herbs and their phytoconstituents with potent antioxidant, anti-inflammatory, and antiapoptotic effects may offer good gastrointestinal protection. Sinapic acid (SA) has potent antioxidant, anti-inflammatory, and antiapoptotic activities ( Raish et al, 2018a ; Bin Jardan et al, 2020 ). The current article reports the first in vivo study of the gastroprotective effects of SA and the underlying mechanism of gastric protection in ethanol-induced GUs in rats.…”