Naringin, a natural flavonone glycoside attenuates N-nitrosodiethylamine- induced hepatocellular carcinoma in sprague-dawley rats

Acharya, Reetuparna; Mishra, Neha; Kumar, Abhishek; Bose, Pritha; Pattnaik, Ashok Kumar; Mukhopadhyay, Kunal; Sunita, Priyashree; Pattanayak, Shakti Prasad

doi:10.4103/pm.pm_94_21

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…Naringin has well-documented efficacy against LPO [55]. Acharya et al [43] also reported that naringin dose-dependently reduced oxidative damage markers, including the LPO marker MDA, consistent with free radical scavenging activity. This suppression of ROS accumulation and enhanced antioxidant capacity also prevents carcinogens from being metabolically activated [56] and decreases ROS-induced mtDNA damage (Figure 9) [57,58].…”

Section: Discussionmentioning

confidence: 81%

“…Similarly, total bilirubin is released due to nonspecific changes in hepatocyte plasma membrane integrity and/or permeability, while ALP elevation results from pathological alterations in biliary flow [42]. All of these increases were reversed by naringin and NDNP, suggesting that these compounds are able to prevent loss of membrane integrity in addition to their effects on the preservation of hepatic functions, such as albumin synthesis [43]. Notably, the nanoformula was more potent in improving liver function and structural integrity than free naringin, likely due to improved bioavailability in liver.…”

Section: Discussionmentioning

confidence: 99%

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Protective Effects of Naringin–Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation

et al. 2022

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Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin–dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Protective Effects of Naringin–Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation

et al. 2022

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“…showed a damaged architecture with irregular and larger hepatocytes consisting of prominent nuclei in Sprague–Dawley rats. Treatment with naringin at 30 and 60 mg/kg/day reversed the damaged hepatic architecture and lobules as fewer pyknotic nuclei were observed along with focal degeneration and mild necrosis (Acharya et al, 2021). Rats also showed the presence of more than one nucleolus, darkened nuclei with variable size, intranuclear vacuoles, enlarged fatty change, loss of lobular architecture, proliferation of bile duct, necrosis, dilatation of hepatic sinusoids with Kupffer cell, and hyperplasia (Akshatha et al, 2018).…”

Section: Biochemical Enzymes Affected By Ndeamentioning

confidence: 99%

A systematic review on multipotent carcinogenic agent, N‐nitrosodiethylamine (NDEA), its major risk assessment, and precautions

Janmeda,

Jain,

Chaudhary

et al. 2024

J of Applied Toxicology

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The International Agency for Research on Cancer has classified N‐nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA‐directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA‐induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA‐directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.

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Role of bitter contributors and bitter taste receptors: a comprehensive review of their sources, functions and future development

Zhou,

Wang,

Huang

et al. 2024

Food Science and Human Wellness

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Bitterness, one of the 5 "basic tastes", is usually undesired by humans. However, abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors. This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits. The main bitter contributors, including phenolics, terpenoids, alkaloids, amino acids, nucleosides and purines, were summarized. The bioactivities and wide range of beneficial effects of them on anti-cancers, anti-inflammations, anti-microbes, neuroprotection, inhibiting chronic and acute injury in organs, as well as regulating behavior performance and metabolism were reported. Furthermore, not only did the bitter taste receptors (taste receptor type 2 family, T2Rs) show taste effects, but extra-oral T2Rs could also be activated by binding with bitter components, regulating physiological activities via modulating hormone secretion, immunity, metabolism, and cell proliferation. This review provided a new perspective on exploring and explaining the nutrition of bitter foods, revealing the relationship between the functions of bitter contributors from food and T2Rs. Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases, exploring the mechanism of T2Rs mediating the bioactivities, and making bitter foods more acceptable without getting rid of bitter contributors.

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Naringin, a natural flavonone glycoside attenuates N-nitrosodiethylamine- induced hepatocellular carcinoma in sprague-dawley rats

Cited by 3 publications

References 53 publications

Protective Effects of Naringin–Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation

Protective Effects of Naringin–Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation

A systematic review on multipotent carcinogenic agent, N‐nitrosodiethylamine (NDEA), its major risk assessment, and precautions

Role of bitter contributors and bitter taste receptors: a comprehensive review of their sources, functions and future development

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