Reduction of Hepatic Steatosis, Oxidative Stress, Inflammation, Ballooning and Insulin Resistance After Therapy with Safranal in NAFLD Animal Model: A New Approach

Abstract

Introduction Non-alcoholic fatty liver disease (NAFLD) is intimately linked to hepatic steatosis, inflammation, insulin resistance (IR), oxidative stress (OS), and ballooning. A high fat diet (HFD) is considered a major etiological factor that primarily covers the numerous features of NAFLD. Methods The present study aimed to evaluate the protective effect of safranal on hepatic steatosis, OS, liver index, IR index, liver function enzymes, plasma lipids, TNF-α, malondialdehyde (MDA), advanced oxidation protein products (AOPPs) and nitrite (NO 2 – ) levels in a NAFLD rat model fed with a HFD for 12 weeks. The ELISA kits were used to measure TNF-α and insulin in serum and plasma, respectively. Results HFD significantly induced hepatic steatosis, OS, IR, liver, and oxidative enzyme elevation and inflammation in experimental animals. Rats treated with safranal in ascending order of doses 250 and 500 mg/kg orally for 4-weeks showed a reduction in hepatic lipid’s accumulation, liver index, hepatic enzymes, collagen, hepatic oxidonitrative stress markers (like AOPP, MDA and NO 2 – ), and raised the levels of catalase (CAT) and superoxide dismutase (SOD) enzymes. Glutathione system components, namely glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were also restored in the safranal-treated groups. The reduction in serum TNF-α and IR provided further support to the anti-NAFLD effect of safranal. Moreover, the histopathological images indicated reverse of NAFLD activity score (NAS) through mild fatty degeneration, ballooning and inflammation in hepatocytes of treated groups. Conclusion Findings of blood and tissue analysis concluded that safranal can be a good choice in the management and cure of NAFLD.

The Effects of Chia Defatted Flour as a Nutritional Supplement in C57BL/6 Mice Fed a Low-Quality Diet

“…In this study, the LNQ diet caused higher protein damage compared to C with significant differences only in the liver, even when the ROS did not show any significant differences in this tissue (probably due to a low-sensitivity technique). Sabir et al [ 40 ] found elevated AOPP levels in the liver of male Sprague–Dawley rats fed a high-fat diet, correlated with an increase in the reactive nitrogen species. Hence, the protein damage observed in this study could also be produced by other mechanisms apart from the ROS.…”

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases

“…Although MAFLD is a new term adopted in the last few years, previous animal studies on fatty liver disease, such as those mentioned in this study, have extensively unraveled the pathogenesis of MAFLD rather than NAFLD. These studies mostly used diet-induced fatty liver disease models, such as high-fat diet-induced fatty liver model and high-fat and high-sugar diet-induced fatty liver model, which can simultaneously induce liver steatosis, obesity, dyslipidemia, and other components of metabolic syndrome, suggesting that despite their titles, they mostly studied the pathogenesis and treatment of MAFLD instead of NAFLD [180][181][182]. Furthermore, recent studies on the pathogenesis and treatment of MAFLD have employed the same methods to induce the disease [183][184][185].…”

Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis

“…There is a crosstalk between parenchymal and non-parenchymal cells, where different mediators are released to activate multiple signaling pathways viciously, all of which directly or indirectly trigger HSC activation and fibrosis (Fangming Yang et al, 2021). The molecular pathways are illustrated in Figure 1 (Mashek, 2021;Sabir, Irfan, Ullah, et al, 2022). Injury-induced inflammation drives the recruitment of macrophages and KCs during fibrogen- HSC proliferation, and inhibit their apoptosis (Foglia et al, 2019;Tang et al, 2017).…”