Sodium Orthovanadate (SOV) mitigates alcohol & alcohol plus high-fat diet (HFD)-induced hepatotoxicity in rats.

Hema Rani, Anjana Devi, Navdeep Singh
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Abstract

Alcoholic fatty liver disease (AFLD) is a leading cause of chronic liver disease worldwide, contributing to significant morbidity and mortality. Despite its growing prevalence, no FDA-approved pharmacological treatments exist, leaving lifestyle modifications as the primary intervention. AFLD pathogenesis involves a complex interplay of lipid accumulation, oxidative stress, insulin resistance, and inflammation, highlighting the need for innovative therapeutic approaches. However, sodium orthovanadate (SOV), an inorganic vanadium-based compound, is a potent inhibitor of protein tyrosine phosphatases (PTPs), including PTP1B-a key regulator of insulin signalling and metabolic homeostasis. SOV has demonstrated insulin-mimetic properties and has shown promise in preclinical models of metabolic disorders. Given the emerging role of PTP1B in hepatic insulin resistance and lipid dysregulation, we hypothesize that SOV may offer therapeutic benefits in AFLD by modulating biochemical parameters and oxidative stress in liver. In this study, we investigate the effects of SOV in two rodent models of AFLD: (1) alcohol-induced liver disease and (2) high-fat diet plus alcohol-induced liver disease. We assess Biochemical Parameters like alkaline Phosphatase (ALP), aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), total bilirubin, cholesterol, uric acid, triglyceride. Tissue analysis like TBARS/MDA activity, Glutathione (reduced GSH) assay, Glutathione peroxidase (GPx) activity, Superoxide Dismutase, Catalase activity, and Histopathology to determine whether SOV can mitigate AFLD progression. Our research shows that SOV has promise as a treatment for fatty liver disease brought on by alcohol. Improvements in oxidative stress control,biochemical markers most likely mediate its hepatoprotective benefits. By uncovering the therapeutic potential of SOV, this study may pave the way for novel pharmacological strategies to combat fatty liver diseases.

正钒酸钠(SOV)减轻酒精和酒精加高脂肪饮食(HFD)引起的大鼠肝毒性。
酒精性脂肪性肝病(AFLD)是世界范围内慢性肝病的主要原因,导致显著的发病率和死亡率。尽管它的发病率越来越高,但目前还没有fda批准的药物治疗方法,改变生活方式是主要的干预措施。AFLD的发病机制涉及脂质积累、氧化应激、胰岛素抵抗和炎症等复杂的相互作用,因此需要创新的治疗方法。然而,正钒酸钠(SOV)是一种无机钒基化合物,是蛋白酪氨酸磷酸酶(PTPs)的有效抑制剂,包括ptp1b -胰岛素信号传导和代谢稳态的关键调节因子。SOV已经证明了胰岛素模拟特性,并在代谢紊乱的临床前模型中显示出前景。鉴于PTP1B在肝脏胰岛素抵抗和脂质失调中的新作用,我们假设SOV可能通过调节肝脏的生化参数和氧化应激来治疗AFLD。在本研究中,我们研究了SOV在两种AFLD啮齿动物模型中的作用:(1)酒精性肝病和(2)高脂肪饮食加酒精性肝病。我们评估生化参数如碱性磷酸酶(ALP)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、乳酸脱氢酶(LDH)、总胆红素、胆固醇、尿酸、甘油三酯。组织分析,如TBARS/MDA活性、谷胱甘肽(还原性谷胱甘肽)测定、谷胱甘肽过氧化物酶(GPx)活性、超氧化物歧化酶、过氧化氢酶活性和组织病理学,以确定SOV是否可以减轻AFLD的进展。我们的研究表明,SOV有望成为酒精引起的脂肪肝疾病的治疗方法。氧化应激控制的改善,生化标记物最有可能介导其保护肝脏的作用。通过揭示SOV的治疗潜力,本研究可能为对抗脂肪肝疾病的新药理策略铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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