Browsing by Author "Sehrawat, Abhishek"

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    Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO?1/NLRP3 and TGF-? expression
    (John Wiley and Sons Inc, 2023-10-16T00:00:00) Patel, Dhaneshvaree; Yadav, Poonam; Singh, Sumeet K.; Tanwar, Sampat S.; Sehrawat, Abhishek; Khurana, Amit; Bhatti, Jasvinder S.; Navik, Umashanker
    Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-?, and IL-6) and fibrosis-related genes (TGF-? and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN. � 2023 Wiley Periodicals LLC.
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    Dysregulated autophagy: A key player in the pathophysiology of type 2 diabetes and its complications
    (Elsevier B.V., 2023-02-14T00:00:00) Sehrawat, Abhishek; Mishra, Jayapriya; Mastana, Sarabjit Singh; Navik, Umashanker; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    Autophagy is essential in regulating the turnover of macromolecules via removing damaged organelles, misfolded proteins in various tissues, including liver, skeletal muscles, and adipose tissue to maintain the cellular homeostasis. In these tissues, a specific type of autophagy maintains the accumulation of lipid droplets which is directly related to obesity and the development of insulin resistance. It appears to play a protective role in a normal physiological environment by eliminating the invading pathogens, protein aggregates, and damaged organelles and generating energy and new building blocks by recycling the cellular components. Ageing is also a crucial modulator of autophagy process. During stress conditions involving nutrient deficiency, lipids excess, hypoxia etc., autophagy serves as a pro-survival mechanism by recycling the free amino acids to maintain the synthesis of proteins. The dysregulated autophagy has been found in several ageing associated diseases including type 2 diabetes (T2DM), cancer, and neurodegenerative disorders. So, targeting autophagy can be a promising therapeutic strategy against the progression to diabetes related complications. Our article provides a comprehensive outline of understanding of the autophagy process, including its types, mechanisms, regulation, and role in the pathophysiology of T2DM and related complications. We also explored the significance of autophagy in the homeostasis of ?-cells, insulin resistance (IR), clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues. This will further pave the way for developing novel therapeutic strategies for diabetes-related complications. � 2023 Elsevier B.V.
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    Lifestyle modifications and nutrition in Alzheimer's disease
    (Elsevier, 2023-06-16T00:00:00) Bhatti, Gurjit Kaur; Mishra, Jayapriya; Sehrawat, Abhishek; Sharma, Eva; Kanozia, Rubal; Navik, Umashanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    Alzheimer's disease (AD) is a progressive chronic neurodegenerative disorder that is increasingly seen in developed and developing countries that subjugate older people. The exacerbation begins with the disease seen with the symptoms like deterioration of mental ability, memory, and cognitive deficits, which ultimately decline the physical activity also, and the severity of this disease causes the death of the patient. There is no proper medication and cure available to date, which can precisely prevent the condition efficiently. But it is essential to diagnose it before its destructive phase and consult for necessary treatments and procedures taken by the patient and the caregivers. Apart from clinical trials, the first and foremost thing is to focus on lifestyle; a way of living can have a more significant impact on a person's health. One can stay healthy for a longer time or fight against the disease by developing strategies like boosting immunity and staying physically fit enough, or else, one can successfully delay the appearance of disease with strong immunity and a healthier lifestyle. And the other promising fact is taking nutritious food, which is helpful to build a robust internal defense system against the diseased condition and lowering the risk of ailments. This chapter will focus on the pathophysiology of Alzheimer's disease, lifestyle modifications, and nutritional interventions in AD. � 2023 Elsevier Inc. All rights reserved.
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    Modulating autophagy and mitophagy as a promising therapeutic approach in neurodegenerative disorders
    (Elsevier Inc., 2022-11-04T00:00:00) Mishra, Jayapriya; Bhatti, Gurjit Kaur; Sehrawat, Abhishek; Singh, Charan; Singh, Arti; Reddy, Arubala P.; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    The high prevalence of neurodegenerative diseases has become a major public health challenge and is associated with a tremendous burden on individuals, society and federal governments worldwide. Protein misfolding and aggregation are the major pathological hallmarks of several neurodegenerative disorders. The cells have evolved several regulatory mechanisms to deal with aberrant protein folding, namely the classical ubiquitin pathway, where ubiquitination of protein aggregates marks their degradation via lysosome and the novel autophagy or mitophagy pathways. Autophagy is a catabolic process in eukaryotic cells that allows the lysosome to recycle the cell's own contents, such as organelles and proteins, known as autophagic cargo. Their most significant role is to keep cells alive in distressed situations. Mitophagy is also crucial for reducing abnormal protein aggregation and increasing organelle clearance and partly accounts for maintaining cellular homeostasis. Furthermore, substantial data indicate that any disruption in these homeostatic mechanisms leads to the emergence of several age-associated metabolic and neurodegenerative diseases. So, targeting autophagy and mitophagy might be a potential therapeutic strategy for a variety of health conditions. � 2022
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    Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives
    (Elsevier Inc., 2022-04-07T00:00:00) Bhatti, Jasvinder Singh; Sehrawat, Abhishek; Mishra, Jayapriya; Sidhu, Inderpal Singh; Navik, Umashanker; Khullar, Naina; Kumar, Shashank; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra
    Type 2 diabetes (T2DM) is a persistent metabolic disorder rising rapidly worldwide. It is characterized by pancreatic insulin resistance and ?-cell dysfunction. Hyperglycemia induced reactive oxygen species (ROS) production and oxidative stress are correlated with the pathogenesis and progression of this metabolic disease. To counteract the harmful effects of ROS, endogenous antioxidants of the body or exogenous antioxidants neutralise it and maintain bodily homeostasis. Under hyperglycemic conditions, the imbalance between the cellular antioxidant system and ROS production results in oxidative stress, which subsequently results in the development of diabetes. These ROS are produced in the endoplasmic reticulum, phagocytic cells and peroxisomes, with the mitochondrial electron transport chain (ETC) playing a pivotal role. The exacerbated ROS production can directly cause structural and functional modifications in proteins, lipids and nucleic acids. It also modulates several intracellular signaling pathways that lead to insulin resistance and impairment of ?-cell function. In addition, the hyperglycemia-induced ROS production contributes to micro- and macro-vascular diabetic complications. Various in-vivo and in-vitro studies have demonstrated the anti-oxidative effects of natural products and their derived bioactive compounds. However, there is conflicting clinical evidence on the beneficial effects of these antioxidant therapies in diabetes prevention. This review article focused on the multifaceted role of oxidative stress caused by ROS overproduction in diabetes and related complications and possible antioxidative therapeutic strategies targeting ROS in this disease. � 2022 Elsevier Inc.
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    Protective role of natural products and bioactive compounds in multiple sclerosis
    (Elsevier, 2023-06-16T00:00:00) Bhatti, Gurjit Kaur; Singh, Harsh Vikram; Sharma, Eva; Sehrawat, Abhishek; Mishra, Jayapriya; Navik, Umashanker; Hemachandra Reddy, P.; Bhatti, Jasvinder Singh
    Multiple sclerosis (MS), a chronic multifactorial disease characterized by progressive demyelination and neurodegeneration, is rising rapidly in young adults. The pathology of the disease is not yet understood completely. However, neuroinflammation, oxidative stress, and hyperactive autoimmune response appear to play a prominent role in the pathogenesis of the disease. Several genetic, nongenetic, and environmental factors are also found associated with this autoimmune disorder. Although, it is still a matter of debate whether diet and lifestyle have an influence during the course of MS. Recent studies have highlighted several beneficial characteristics of natural bioactive compounds such as anti-inflammatory, antioxidative, immunomodulatory, and other neuroprotective effects, indicating their therapeutic potential to reduce the risk or ameliorate the progression of MS. Basically, these bioactive compounds are the chemicals found in minute amounts naturally in plants with peculiar health benefits. In this chapter, we have briefly described various natural bioactive compounds with neuroprotective effects against MS, including the polyphenols, vitamins supplementation, and natural products such as ginger, ashwagandha, and it seems that these compounds play a notable role in the treatment of MS. Further research is required to extend our understanding in developing more effective therapeutic strategies against the disease with lesser side effects. � 2023 Elsevier Inc. All rights reserved.
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    Stem cells in the treatment of Alzheimer's disease � Promises and pitfalls
    (Elsevier B.V., 2023-04-06T00:00:00) Bhatti, Jasvinder Singh; Khullar, Naina; Mishra, Jayapriya; Kaur, Satinder; Sehrawat, Abhishek; Sharma, Eva; Bhatti, Gurjit Kaur; Selman, Ashley; Reddy, P. Hemachandra
    Alzheimer's disease (AD) is the most widespread form of neurodegenerative disorder that causes memory loss and multiple cognitive issues. The underlying mechanisms of AD include the build-up of amyloid-? and phosphorylated tau, synaptic damage, elevated levels of microglia and astrocytes, abnormal microRNAs, mitochondrial dysfunction, hormonal imbalance, and age-related neuronal loss. However, the etiology of AD is complex and involves a multitude of environmental and genetic factors. Currently, available AD medications only alleviate symptoms and do not provide a permanent cure. Therefore, there is a need for therapies that can prevent or reverse cognitive decline, brain tissue loss, and neural instability. Stem cell therapy is a promising treatment for AD because stem cells possess the unique ability to differentiate into any type of cell and maintain their self-renewal. This article provides an overview of the pathophysiology of AD and existing pharmacological treatments. This review article focuses on the role of various types of stem cells in neuroregeneration, the potential challenges, and the future of stem cell-based therapies for AD, including nano delivery and gaps in stem cell technology. � 2023 Elsevier B.V.
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    Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease
    (Elsevier Inc., 2023-08-02T00:00:00) Kaur, Satinder; Sehrawat, Abhishek; Mastana, Sarabjit Singh; Kandimalla, Ramesh; Sharma, Pushpender Kumar; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory. � 2023 Elsevier Inc.