Cardioprotective effect of zingerone against oxidative stress, inflammation, and apoptosis induced by cisplatin or gamma radiation in rats

Abstract

Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes' activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.

Otoprotective Effects of Zingerone on Cisplatin-Induced Ototoxicity

“…In the present study, CXP-induced apoptosis related to caspase 3 was attenuated in the cochlea in the ZO cotreatment group, although the caspase 3 level in this group was still higher than that in the control group. The immediate inflammatory and apoptotic responses after CXP administration could not be reversed in this study because ZO and CXP were simultaneously administered; in contrast, in previous studies, ZO was administered before CXP was injected [21,22]. Moreover, although ZO showed protective effects against oxidative stress and inflammation, it could not prevent activation of other apoptotic pathways, such as the intrinsic pathway involving mitochondrial cytochrome c and caspases 9, 6, and 7 [31] or activation of the transient receptor potential vanilloid 1 channel in cochlear hair cells [32].…”

“…Zingerone (ZO; 4-para methoxy-4-hydroxyphenyl-2-butanone) has antioxidant, anti-inflammatory, and antiapoptotic effects [15] that are presumed to be related to its protective effects against radiationinduced intestinal injury [16], lipopolysaccharide-induced liver damage [17], and sepsis-triggered nephrotoxicity [18]. Moreover, ZO has protective effects against CXP-induced toxicities, such as nephrotoxicity [15,19], hepatotoxicity [20], cardiotoxicity [21], and ovarian and uterine toxicity [22]. Because the molecular mechanisms underlying CXP-induced nephrotoxicity overlap with those underlying CXP-induced ototoxicity [23], it would be reasonable to expect that ZO has otoprotective effects against CXP-induced ototoxicity.…”

Protective effects of zingerone derivate on ionizing radiation-induced intestinal injury

“…Caspase-3 is an apoptotic executor, which was used as an indicator of intestinal cell apoptosis in our study [ 31 , 32 ]. Caspase-3 gene expression in γ-radiation-induced cardiac apoptosis was significantly downregulated by zingerone in previous reports [ 33 ]. In this study, apoptosis was reduced in the TZC01 group compared with the Solvent group.…”

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

“…Moreover, mitochondrial DNA injury and nuclear DNA damage were observed. Antioxidant natural products such as tutin (vitamin P1), zingerone and cyanidin can inhibit cisplatin-induced inflammatory infiltration, DNA damage, and mitochondrial dysfunction, indicating the key role of oxidative stress in cisplatin-induced cardiomyocyte apoptosis (Qian et al, 2018;Soliman et al, 2018;Topal et al, 2018).…”