Abstract:Increased prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the consequences of the current obesity epidemic. NAFLD is a major form of chronic liver disease that is highly prevalent in obese and overweight adults and children. Nonalcoholic steatohepatitis (NASH) is the severe form of NAFLD, and uncontrolled inflammation as displayed in NASH has been identified as one of the key events in enhancing hepatic carcinogenesis. Lycopene is a non-provitamin A carotenoid and the pigment principally resp… Show more
“…Lycopene can accumulate in adipose tissue (10) and modulate adipose lipid/inflammationassociated signaling cascades (41,42). Evidence showed that the portal vein directly connects the liver with the visceral MAT (43,44), and visceral fat content is highly correlated with the degree of liver steatosis in humans (45,46).…”
Section: Discussionmentioning
confidence: 98%
“…In vivo and in vitro studies have suggested that lycopene may use multifaceted mechanisms to reduce CVD and NAFLD risks (8)(9)(10), mechanisms that include modulating cholesterol metabolism, serving as an antioxidant, and inhibiting inflammation (8)(9)(10). Of note, NAFLD patients have substantially reduced plasma lycopene concentration (11), suggesting potential interactions between low lycopene status and CVD risk.…”
Our data suggest that lycopene and APO10LA inhibit HSFD-induced steatosis in BCO2-KO male mice through differential mechanisms. Sex disparity of BCO2-KO mice was observed in the outcomes of HSFD-induced liver steatosis and plasma lipids.
“…Lycopene can accumulate in adipose tissue (10) and modulate adipose lipid/inflammationassociated signaling cascades (41,42). Evidence showed that the portal vein directly connects the liver with the visceral MAT (43,44), and visceral fat content is highly correlated with the degree of liver steatosis in humans (45,46).…”
Section: Discussionmentioning
confidence: 98%
“…In vivo and in vitro studies have suggested that lycopene may use multifaceted mechanisms to reduce CVD and NAFLD risks (8)(9)(10), mechanisms that include modulating cholesterol metabolism, serving as an antioxidant, and inhibiting inflammation (8)(9)(10). Of note, NAFLD patients have substantially reduced plasma lycopene concentration (11), suggesting potential interactions between low lycopene status and CVD risk.…”
Our data suggest that lycopene and APO10LA inhibit HSFD-induced steatosis in BCO2-KO male mice through differential mechanisms. Sex disparity of BCO2-KO mice was observed in the outcomes of HSFD-induced liver steatosis and plasma lipids.
“…Table 1 reports a brief description of some foods characterizing Sicilian countryside dietary habits [27,28,29,30,31,32]. As previously stated, olive oil plays a central role in MedDiet [2,11,33,34,35] and a glass of wine with meals may be assumed every day [2,11].…”
Section: Mediterranean Diet Nutrients Phytochemicals and Hormesismentioning
Traditional Mediterranean diet (MedDiet) is a common dietary pattern characterizing a lifestyle and culture proven to contribute to better health and quality of life in Mediterranean countries. By analyzing the diet of centenarians from the Sicani Mountains and eating habits of inhabitants of Palermo, it is reported that a close adherence to MedDiet is observed in the countryside, whereas in big towns this adherence is not so close. This has an effect on the rates of mortality at old age (and reciprocally longevity) that are lower in the countryside than in big towns. Concerning the health effects of the diet, the low content of animal protein and the low glycaemic index of the Sicilian MedDiet might directly modulate the insulin/IGF-1 and the mTOR pathways, known to be involved in ageing and longevity. In particular, the reduction of animal protein intake may significantly reduce serum IGF-1 concentrations and inhibit mTOR activity with a down-regulation of the signal that leads to the activation of FOXO3A and, consequently, to the transcription of homeostatic genes that favour longevity. The down-regulation of both IGF-1 and mTORC1 also induces an anti-inflammatory effect. In addition to the effects on sensing pathways, many single components of MedDiet are known to have positive effects on health, reducing inflammation, optimizing cholesterol and other important risk factors of age-related diseases. However, a key role is played by polyphenols represented in high amount in the Sicilian MedDiet (in particular in extra virgin olive oil) that can work as hormetins that provide an environmental chemical signature regulating stress resistance pathways such as nuclear factor erythroid 2-related factor 2.
“…Lycopene has been shown to activate the Nrf2/ HO-1 pathway and can protect against nephrotoxicity induced by gentamicin, adriamycin, and cisplatin (28,31,(36)(37)(38)(39). Lycopene displays antioxidant and anti-inflammatory effects; in one clinical trial, the data suggested that it may play an important role in protection against various chronic diseases (e.g., cancer) (40). In the present study, we investigated the nephroprotective effect of lycopene on polymyxin-induced nephrotoxicity and the involvement of the Nrf2/HO-1 pathway in a mouse model.…”
bNephrotoxicity is the major dose-limiting factor for the clinical use of colistin against multidrug-resistant (MDR) Gram-negative bacteria. This study aimed to investigate the protective effect of lycopene on colistin-induced nephrotoxicity in a mouse model. Fifty mice were randomly divided into 5 groups: the control group (saline solution), the lycopene group (20 mg/kg of body weight/day administered orally), the colistin group (15 mg/kg/day administered intravenously), the colistin (15 mg/kg/day) plus lycopene (5 mg/kg/day) group, and the colistin (15 mg/kg/day) plus lycopene (20 mg/kg/day) group; all mice were treated for 7 days. At 12 h after the last dose, blood was collected for measurements of blood urea nitrogen (BUN) and serum creatinine levels. The kidney tissue samples were obtained for examination of biomarkers of oxidative stress and apoptosis, histopathological assessment, and quantitative reverse transcription-PCR (qRT-PCR) analysis. Colistin treatment significantly increased concentrations of BUN and serum creatinine, tubular apoptosis/necrosis, lipid peroxidation, and heme oxygenase 1 (HO-1) activity, while the treatment decreased the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Notably, the changes in the levels of all biomarkers were attenuated in the kidneys of mice treated with colistin by lycopene (5 or 20 mg/kg). Lycopene treatment, especially in the colistin plus lycopene (20 mg/kg) group, significantly downregulated the expression of NF-B mRNA (P < 0.01) but upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (both P < 0.01) in the kidney compared with the results seen with the colistin group. Our data demonstrated that coadministration of 20 mg/kg/day lycopene can protect against colistin-induced nephrotoxicity in mice. This effect may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.
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