Supplementation of Saponins from Leaves of Panax quinquefolius Mitigates Cisplatin-Evoked Cardiotoxicity via Inhibiting Oxidative Stress-Associated Inflammation and Apoptosis in Mice

Abstract

Background: Although kidney injury caused by cisplatin has attracted much attention, cisplatin-induced cardiotoxicity is elusive. Our previous studies have confirmed that saponins (ginsenosides) from Panax quinquefolius can effectively reduce acute renal injuries. Our current study aimed to identify the potential effects of saponins from leaves of P. quinquefolius (PQS) on cisplatin-evoked cardiotoxicity. Methods: Mice were intragastrically with PQS at the doses of 125 and 250 mg/kg daily for 15 days. The mice in cisplatin group and PQS + cisplatin groups received four times intraperitoneal injections of cisplatin (3 mg/kg) two days at a time from the 7th day, respectively. All mice were killed at 48 h following final cisplatin injection. Body weights, blood and organic samples were collected immediately. Results: Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with obvious histopathological changes and elevation of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT) concentrations and viabilities in serum. Cisplatin also impaired antioxidative defense system in heart tissues manifested by a remarkable reduction in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, demonstrating the overproduction of reactive oxygen species (ROS) and oxidative stress. Interestingly, PQS (125 and 250 mg/kg) can attenuate cisplatin-evoked changes in the above-mentioned parameters. Additionally, PQS administration significantly alleviated the oxidation resulted from inflammatory responses and apoptosis in cardiac tissues via inhibition of overexpressions of TNF-α, IL-1β, Bax, and Bad as well as the caspase family members like caspase-3, and 8, respectively. Conclusion: Findings from our present research clearly indicated that PQS exerted significant effects on cisplatin-induced cardiotoxicity in part by inhibition of the NF-κB activity and regulation of PI3K/Akt/apoptosis mediated signaling pathways.

Saponins Extracted from Tea (Camellia Sinensis) Flowers Induces Autophagy in Ovarian Cancer Cells

“…Natural saponins from tea (Camellia sinensis) flowers possess remarkable structural diversity and have become increasingly important compounds for the prevention and treatment of cancer and other diseases [29][30][31]. Several triterpenoid saponins have demonstrated the ability to induce autophagy of cancer cells in various cancer cells lines [32,33].…”

N6-2-hydroxyethyl-adenosine ameliorate cisplatin induced acute kidney injury in mice

“…Cisplatin is one of the most frequently used drugs in the treatment of a number of malignancies, cancers and solid tumors. However, its clinical application has been limited due to multiple toxicities and side effects accrued from its usage (Xing et al 2019;Yucetas et al 2019;Zhang et al 2019). A lot of convincing evidences have implicated ROS generation, oxidative stress and inflammation as the main culprit responsible for cisplatin-evoked toxicity including nephrotoxicity (Arafa and Atteia 2019;Li et al 2018).…”

Clinical Insights into Cisplatin-Induced Arrhythmia in a Patient with Locally Advanced Non-Small Cell Lung Cancer: A Case Report

“…Hence, the actual incidence of cardiotoxic events ascribed to cisplatin might be underestimated [18]. The various possible mechanisms underpinning cisplatin-induced cardiac dysfunction remain under investigation [19]. Drug-induced damage to cardiac myocytes or blood vessels, the electrical conduction system, or the pericardium are possible underlying mechanisms according to existing studies [7,20].…”

“…Drug-induced damage to cardiac myocytes or blood vessels, the electrical conduction system, or the pericardium are possible underlying mechanisms according to existing studies [7,20]. Pathological mechanisms including induction of coronary vasospasm, damage of the vascular endothelium, oxidative and nitrosative stress, and electrolyte imbalance are frequently associated with acute complications, whereas cardiomyopathy may be the cause of late complications [13,15,19]. Moreover, it is published that cisplatin could deposit in tissues such as the liver, skin and kidneys and be detectable in blood 20 years after completion of a cisplatin infusion.…”