Browsing by Author "Jaiswal, Aiswarya"

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Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity
(Elsevier Inc., 2023-09-24T00:00:00) Jaiswal, Aiswarya; Rawat, Pushkar Singh; Singh, Sumeet Kumar; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limited due to its cardiotoxicity, including congestive heart failure, alterations in myocardial structure, arrhythmia, and left ventricular dysfunction. Dox causes cardiotoxicity via various mechanisms, including oxidative stress, mitochondrial dysfunctioning, deranged Ca2+ homeostasis, inflammation, fibrosis, downregulating AMPK, etc. Betaine is a zwitterion-based drug known as N, N, N trimethylglycine that regulates the methionine cycle and homocysteine (a risk factor for cardiovascular disease) detoxification through betaine-homocysteine methyltransferases. Betaine is nontoxic and has several beneficial effects in different disease models. Betaine treatment decreases the amyloid ? generation, reduces obesity, improves steatosis and fibrosis, and activates AMP-activated protein kinase (AMPK). Further, betaine downregulates 8?hydroxy-2-deoxyguanosine, malondialdehyde, and upregulates catalases, glutathione peroxidase, and superoxide dismutase activity. Therefore, we hypothesized that betaine might be a rational drug candidate to effectively combat Dox-associated oxidative stress, inflammation, and mitochondrial dysfunction. � 2023 The Author(s)
Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management
(Elsevier Masson s.r.l., 2021-05-13T00:00:00) Rawat, Pushkar Singh; Jaiswal, Aiswarya; Khurana, Amit; Bhatti, Jasvinder Singh; Navik, Umashanker
Doxorubicin (Dox) is a secondary metabolite of the mutated strain of Streptomyces peucetius var. Caesius and belongs to the anthracyclines family. The anti-cancer activity of Dox is mainly exerted through the DNA intercalation and inhibiting topoisomerase II enzyme in fast-proliferating tumors. However, Dox causes cumulative and dose-dependent cardiotoxicity, which results in increased risks of mortality among cancer patients and thus limiting its wide clinical applications. There are several mechanisms has been proposed for doxorubicin-induced cardiotoxicity and oxidative stress, free radical generation and apoptosis are most widely reported. Apart from this, other mechanisms are also involved in Dox-induced cardiotoxicity such as impaired mitochondrial function, a perturbation in iron regulatory protein, disruption of Ca2+ homeostasis, autophagy, the release of nitric oxide and inflammatory mediators and altered gene and protein expression that involved apoptosis. Dox also causes downregulation of DNA methyltransferase 1 (DNMT1) enzyme activity which leads to a reduction in the DNA methylation process. This hypomethylation causes dysregulation in the mitochondrial genes like peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1-alpha (PGC-1?), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) unit in the heart. Apart from DNA methylation, Dox treatment also alters the micro RNAs levels and histone deacetylase (HDAC) activity. Therefore, in the current review, we have provided a detailed update on the current understanding of the pathological mechanisms behind the well-known Dox-induced cardiotoxicity. Further, we have provided some of the most plausible pharmacological strategies which have been tested against Dox-induced cardiotoxicity. � 2021 The Authors
Novel pharmacological approaches for diabetic complications
(Nova Science Publishers, Inc., 2021-03-24T00:00:00) Arora, Anchal; Navik, Uma Shanker; Jaiswal, Aiswarya; Kaur, Prabhsharan; Kumar, Puneet
Diabetes is a chronic illness characterized by uncontrolled hyperglycemia, disturbances in carbohydrate, and lipid and protein metabolism due to impaired function of insulin-secreting pancreatic ?-cell, insulin action or both. If not treated on time diabetes patients are more prone to developing secondary complications such as microvascular complications, including nephropathy, retinopathy, neuropathy, diabetic foot, dermopathy, and macrovascular complications like coronary arteries disease, peripheral arterial disease, stroke and cardiomyopathy. This increases the co-morbidity and mortality rate among diabetes patients. Therefore, hyperglycemia management could be of profound clinical significance to reduce the rate of complications of diabetes. Further, hyperglycemia results in the activation of multiple abnormal signaling pathways that poses more complex diabetes pathology resulting in end-organ damage. Traditionally, the available approved therapy, such as insulin and sulphonylureas, possesses side effects such as weight gain and hypoglycaemic shock. Therefore developing a novel therapy for targeting complex pathways for mitigating diabetes complications is highly appreciable. Hence, this chapter aims to discuss the novel therapeutic approaches for treating diabetes complications with their mechanism of action. � 2021 Nova Science Publishers, Inc.