Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models
Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential lon...
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MDPI AG
2023-01-01
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author | Bernice Asiedu Busisani Wiseman Lembede Monica Gomes Abe Kasonga Pilani Nkomozepi Trevor Tapiwa Nyakudya Eliton Chivandi |
author_facet | Bernice Asiedu Busisani Wiseman Lembede Monica Gomes Abe Kasonga Pilani Nkomozepi Trevor Tapiwa Nyakudya Eliton Chivandi |
author_sort | Bernice Asiedu |
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description | Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague–Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12–21: group 1—nutritive milk (NM), group 2—NM +1 g/kg ethanol (Eth), group 3—NM + 40 mg/kg ZO, group 4—NM + Eth +ZO. From PND 46–100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (<i>p</i> < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of <i>SREBP1c</i> and <i>PPAR-α</i> in male and female rats (<i>p</i> < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and <i>SREBP1c</i> upregulation in male rats only and attenuated the alcohol-induced hepatic <i>PPAR-α</i> downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD. |
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spelling | doaj.art-7b6002e024984abab4f3e2ef13080db02023-11-16T22:03:50ZengMDPI AGMetabolites2218-19892023-01-0113216710.3390/metabo13020167Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat ModelsBernice Asiedu0Busisani Wiseman Lembede1Monica Gomes2Abe Kasonga3Pilani Nkomozepi4Trevor Tapiwa Nyakudya5Eliton Chivandi6School of Physiology, Faculty of Health Sciences, University of the Witwaterstrand, 7 York Street, Parktown, Johannesburg 2193, South AfricaSchool of Physiology, Faculty of Health Sciences, University of the Witwaterstrand, 7 York Street, Parktown, Johannesburg 2193, South AfricaSchool of Physiology, Faculty of Health Sciences, University of the Witwaterstrand, 7 York Street, Parktown, Johannesburg 2193, South AfricaDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South AfricaDepartment of Human Anatomy and Physiology, Faculty of Health Sciences, University of Johannesburg, Corner Beit and Siemert Street, Doornfontein, Johannesburg 2094, South AfricaDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South AfricaSchool of Physiology, Faculty of Health Sciences, University of the Witwaterstrand, 7 York Street, Parktown, Johannesburg 2193, South AfricaAlcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague–Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12–21: group 1—nutritive milk (NM), group 2—NM +1 g/kg ethanol (Eth), group 3—NM + 40 mg/kg ZO, group 4—NM + Eth +ZO. From PND 46–100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (<i>p</i> < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of <i>SREBP1c</i> and <i>PPAR-α</i> in male and female rats (<i>p</i> < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and <i>SREBP1c</i> upregulation in male rats only and attenuated the alcohol-induced hepatic <i>PPAR-α</i> downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD.https://www.mdpi.com/2218-1989/13/2/167alcohol-induced fatty liver diseasezingeroneperoxisome proliferator activator receptor-alpha (<i>PPAR-α</i>)sterol regulatory element binding protein 1c (<i>SREBP1c</i>)macrosteatosis |
spellingShingle | Bernice Asiedu Busisani Wiseman Lembede Monica Gomes Abe Kasonga Pilani Nkomozepi Trevor Tapiwa Nyakudya Eliton Chivandi Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models Metabolites alcohol-induced fatty liver disease zingerone peroxisome proliferator activator receptor-alpha (<i>PPAR-α</i>) sterol regulatory element binding protein 1c (<i>SREBP1c</i>) macrosteatosis |
title | Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models |
title_full | Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models |
title_fullStr | Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models |
title_full_unstemmed | Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models |
title_short | Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models |
title_sort | neonatal orally administered zingerone attenuates alcohol induced fatty liver disease in experimental rat models |
topic | alcohol-induced fatty liver disease zingerone peroxisome proliferator activator receptor-alpha (<i>PPAR-α</i>) sterol regulatory element binding protein 1c (<i>SREBP1c</i>) macrosteatosis |
url | https://www.mdpi.com/2218-1989/13/2/167 |
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