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Bromelain Confers Protection against the Non-Alcoholic Fatty Liver Disease in Male C57bl/6 Mice.

ABSTRACT: We aimed to investigate the effect of bromelain, the extract from stems of pineapples on the high-fat diet (HFD)-induced deregulation of hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD), and its underlying mechanism in mice. Mice were daily administrated with HFD with or without bromelain (20 mg/kg) for 12 weeks, and we found that bromelain decreased the HFD-induced increase in body weight by ~30%, organ weight by ~20% in liver weight and ~40% in white adipose tissue weight. Additionally, bromelain attenuated HFD-induced hyperlipidemia by decreasing the serum level of total cholesterol by ~15% and triglycerides level by ~25% in mice. Moreover, hepatic lipid accumulation, particularly that of total cholesterol, free cholesterol, triglycerides, fatty acids, and glycerol, was decreased by 15-30% with bromelain treatment. Mechanistically, these beneficial effects of bromelain on HFD-induced hyperlipidemia and hepatic lipid accumulation may be attributed to the decreased fatty acid uptake and cholesteryl ester synthesis and the increased lipoprotein internalization, bile acid metabolism, cholesterol clearance, the assembly and secretion of very low-density lipoprotein, and the ?-oxidation of fatty acids by regulating the protein expression involved in the above mentioned hepatic metabolic pathways. Collectively, these findings suggest that bromelain has therapeutic value for treating NAFLD and metabolic diseases.

SUBMITTER: Hu PA

PROVIDER: S-EPMC7285019 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Bromelain Confers Protection against the Non-Alcoholic Fatty Liver Disease in Male C57bl/6 Mice.

Hu Po-An PA Chen Chia-Hui CH Guo Bei-Chia BC Kou Yu Ru YR Lee Tzong-Shyuan TS

Nutrients 20200518 5

We aimed to investigate the effect of bromelain, the extract from stems of pineapples on the high-fat diet (HFD)-induced deregulation of hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD), and its underlying mechanism in mice. Mice were daily administrated with HFD with or without bromelain (20 mg/kg) for 12 weeks, and we found that bromelain decreased the HFD-induced increase in body weight by ~30%, organ weight by ~20% in liver weight and ~40% in white adipose tissue weight ...[more]

PMID: 32443556

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Project description:Accounting for genetic and other (eg, underlying disease states) factors that may lead to inter-individual variability in susceptibility to xenobiotic-induced injury is a challenge in human health assessments. A previous study demonstrated that nonalcoholic fatty liver disease (NAFLD), one of the common underlying disease states, enhances tetrachloroethylene (PERC)-associated hepatotoxicity in mice. Interestingly, NAFLD resulted in a decrease in metabolism of PERC to nephrotoxic glutathione conjugates; we therefore hypothesized that NAFLD would protect against PERC-associated nephrotoxicity. Male C57BL/6J mice were fed a low-fat (LFD), high-fat (31% fat, HFD), or high-fat methionine/choline/folate-deficient (31% fat, MCD) diets. After 8 weeks mice were administered either a single dose of PERC (300 mg/kg i.g.) and euthanized at 1-36 h post dose, or five daily doses of PERC (300 mg/kg/d i.g.) and euthanized 4 h after last dose. Relative to LFD-fed mice, HFD- or MCD-fed mice exhibited decreased PERC concentrations and increased trichloroacetate (TCA) in kidneys. S-(1,2,2-trichlorovinyl)glutathione (TCVG), S-(1,2,2-trichlorovinyl)-l-cysteine (TCVC), and N-acetyl-S-(1,2,2,-trichlorovinyl)-l-cysteine (NAcTCVC) were also significantly lower in kidney and urine of HFD- or MCD-fed mice compared with LFD-fed mice. Despite differences in levels of nephrotoxic PERC metabolites in kidney, LFD- and MCD-fed mice demonstrated similar degree of nephrotoxicity. However, HFD-fed mice were less sensitive to PERC-induced nephrotoxicity. Thus, whereas both MCD- and HFD-induced fatty liver reduced the delivered dose of nephrotoxic PERC metabolites to the kidney, only HFD was protective against PERC-induced nephrotoxicity, possibly due to greater toxicodynamic sensitivity induced by methyl and choline deficiency. These results therefore demonstrate that pre-existing disease conditions can lead to a complex interplay of toxicokinetic and toxicodynamic changes that modulate susceptibility to the toxicity of xenobiotics.

Dataset Information

Bromelain Confers Protection against the Non-Alcoholic Fatty Liver Disease in Male C57bl/6 Mice.

Publications

Bromelain Confers Protection against the Non-Alcoholic Fatty Liver Disease in Male C57bl/6 Mice.

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