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 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 (p < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of SREBP1c and PPAR-α in male and female rats (p < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and SREBP1c upregulation in male rats only and attenuated the alcohol-induced hepatic PPAR-α 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.

Orally administered zingerone does not mitigate alcohol-induced hepatic oxidative stress in growing Sprague Dawley rat pups.

Neonatal alcohol exposure (NAE) can induce oxidative stress. We determined whether zingerone (ZO), a phytochemical with anti-oxidant activity, can mitigate the negative impact of neonatal alcohol-induced oxidative stress. Seventy ten-day-old Sprague-Dawley rat pups (35 male, 35 female) were randomly assigned and administered the following treatment regimens daily 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. Growth performance, blood glucose and plasma triglycerides (TGs), total cholesterol, HDL-cholesterol, leptin and insulin concentration were determined. Cytochrome p450E21(CYP2E1) and thiobarbituric acid (TBARS); markers of hepatic oxidative stress and catalase, superoxide dismutase (SOD) and total glutathione (GSH), anti-oxidant markers of the pups were determined. Oral administration of ethanol (NM + Eth), zingerone (NM + ZO) and combined ethanol and zingerone (NM + Eth + ZO) did not affect the growth performance and insulin and leptin concentration of the rats (p > 0.05). Ethanol significantly reduced plasma TGs concentration of female rats (p = 0.04 vs control). However, ethanol and/or its combination with zingerone decreased hepatic GSH (p = 0.02 vs control) and increased CYP2E1 (p = 0.0002 vs control) activity in male rat pups. Zingerone had no effect (p > 0.05 vs control) on the rats' CYP2E1, GSH, SOD and catalase activities. Neonatal alcohol administration elicited hepatic oxidative stress in male rat pups only, showing sexual dimorphism. Zingerone (NM + ZO) prevented an increase in CYP2E1 activity and a decrease in GSH concentration but did not prevent the alcohol-induced hepatic oxidative stress in the male rat pups.

Early-life exposure to alcohol and the risk of alcohol-induced liver disease in adulthood.

Alcohol consumption remains prevalent among pregnant and nursing mothers despite the well-documented adverse effects this may have on the offspring. Moderate-to-high levels of alcohol consumption in pregnancy result in fetal alcohol syndrome (FAS) disorders, with brain defects being chief among the abnormalities. Recent findings indicate that while light-to-moderate levels may not cause FAS, it may contribute to epigenetic changes that make the offspring prone to adverse health outcomes including metabolic disorders and an increased propensity in the adolescent-onset of drinking alcohol. On the one hand, prenatal alcohol exposure (PAE) causes epigenetic changes that affect lipid and glucose transcript regulating genes resulting in metabolic abnormalities. On the other hand, it can program offspring for increased alcohol intake, enhance its palatability, and increase acceptance of alcohol's flavor through associative learning, making alcohol a plausible second hit for the development of alcohol-induced liver disease. Adolescent drinking results in alcohol dependence and abuse in adulthood. Adolescent drinking results in alcohol dependence and abuse in adulthood. Alterations on the opioid system, particularly, the mu-opioid system, has been implicated in the mechanism that induces increased alcohol consumption and acceptance. This review proposes a mechanism that links PAE to the development of alcoholism and eventually to alcoholic liver disease (ALD), which results from prolonged alcohol consumption. While PAE may not lead to ALD development in childhood, there are chances that it may lead to ALD in adulthood.

Zingerone Administered Neonatally Prevents the Subsequent Development of High Dietary Fructose-Induced Fatty Liver in Sprague Dawley Rats.

Consumption of high-fructose diets early in life increases the risk of developing metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Zingerone, an alkaloid isolated from Zingiber officinale, has been demonstrated to reverse obesity and fatty liver in adult male rats. We investigated the potential preventive effects of neonatally administered zingerone on the development of fructose-induced NAFLD in male and female rats. Four-day-old male (n = 35) and female (n = 44) rat pups were randomized and gavaged with: 10 mL/kg body weight (bwt) of distilled water (C), 10 mL/kg bwt of 20% fructose solution (Fr), 10 mL/kg bwt of 20% fructose solution +40 mg/kg bwt of zingerone (ZFr), and 40 mg/kg bwt of zingerone (Z) daily for 14 days. After weaning, all groups continued on unlimited standard rat feed; however, groups C and Z had plain drinking water, whereas groups Fr and ZFr had unlimited 20% fructose solution to drink for 10 weeks. Rats on the high-fructose diet (Fr) compared with the negative controls (C) had significantly increased hepatic lipid content (in %, males: P = .0002; females: P < .0001, analysis of variance [ANOVA]) and hepatic steatosis score (in %, males: P = .0018; females: P < .0022, Kruskal-Wallis ANOVA). Zingerone prevented (P < .05) the fructose-induced increase in hepatic steatosis in both sexes. The plasma alanine aminotransferase activity, levels of uric acid, TBARS (thiobarbituric acid reactive substances), IL-6 (interleukin-6), and TNF-α (tumor necrosis factor alpha) were not different (P > .05, ANOVA) across the different treatment groups in both sexes. No difference (P > .05, ANOVA) was observed between the two sexes for treatment, sex and interaction effects with regard to hepatic lipid content, and measured blood parameters. The use of zingerone neonatally should be further investigated as a strategic prophylactic intervention for the prevention of long-term high-fructose diet-induced NAFLD.

Red milkwood (Mimusops zeyheri) seed meal can replace maize meal in Japanese quail finisher diets without compromising growth performance, feed economy and carcass yield.

Mimusops zeyheri is widely distributed in sub-Saharan Africa and its seed meal (MZSM) has a higher energy content than maize meal (MM). We evaluated the potential of MZSM to substitute MM in Japanese quail finisher diets by determining its effects on growth performance, feed intake (FI) and feed utilisation efficiency, abdominal fat deposition and carcass yield. In a completely randomised design thirty-two 5-weeks old male Japanese quail were allocated to four diets wherein MZSM replaced MM at 0%, 12.5%, 25% and 37.5% (gross energy basis) and fed ad libitum for 4 weeks. Initial and weekly body weight, final body weight (FBW) and daily FI were measured. Body weight gain (BWG), average daily gain (ADG) and feed conversion ratio (FRC) were computed. At the end of the trial, following a 4-hour fast, the quail were weighed then humanely slaughtered and dressed. Carcass weight and dressing percent were determined. Abdominal fat was weighed. MZSM did not affect (P>0.05) the quail's FBW, BWG, ADG, FCR, carcass weight and dressing percent. MZSM at 37.5% inclusion decreased (P<0.0001) FI in weeks 1 and 2 and total FI of the quail. Dietary M. zeyheri seed meal decreased (P<0.0001) abdominal fat mass. Use of MZSM would be most economic at 37.5% inclusion because despite decreasing total FI, growth performance was similar to control. M. zeyheri seed meal can be used as a dietary energy source in Japanese quail finisher diets without compromising growth performance, feed utilisation efficiency and carcass yield.