Neonatal administration of curcumin protects against high fructose diet-induced non-alcoholic steatohepatitis in male adolescent Sprague Dawley rats

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA223

Poster Communications: Neonatal administration of curcumin protects against high fructose diet-induced non-alcoholic steatohepatitis in male adolescent Sprague Dawley rats

K. G. Ibrahim1,2, E. Chivandi1, P. Nkomozepi3, K. Erlwanger1

1. School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johanesburg, Gauteng, South Africa. 2. Department of Physiology, Faculty of Basic Medical Sciences, Usmanu Danfodiyo University, Sokoto, Sokoto, Nigeria. 3. Department of Human Anatomy and Physiology, University of Johannesburg, Johannesburg, Gauteng, South Africa.

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The increased prevalence of non-alcoholic fatty liver disease (NAFLD) which comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), is driven by an increased consumption of fructose. The suckling period in altricial species is characterised by rapid growth and developmental plasticity. Interventions with polyphenols such as S-allyl-l-cysteine in this period have proven benefits in the protection of the animals against adverse consequences of a high fructose diet. Curcumin is a dietary polyphenol with antisteatotic and antifibrotic effects in the liver. We aimed to determine whether neonatal administration of curcumin would protect growing rats against the development of NASH in adolescence when they are fed a high fructose diet. A total of 65, 6-day old male suckling Sprague Dawley pups were used in the study which was conducted in two phases. In the first phase which extended from postnatal day (PN) 6 to PN 21, the pups were allocated to four groups and received treatments as follows: 10ml.kg-1 of a 0.5% dimethyl sulfoxide solution (n=16), curcumin 500mg.kg-1(n=17), fructose (20%, w/v) (n=16) and a combination of curcumin and fructose (n=16). The treatments were administered daily via oral gavage. At weaning, which marked the beginning of the second study phase, the pups in each group were further subdivided into two; one group had normal rat chow and plain tap water while the other received normal rat chow and fructose (20%, w/v) as their drinking fluid. These treatments continued ad libitum for six weeks until PN 63 when the rats were terminated using sodium pentobarbital (150mg.kg-1, i.p). The liver was excised, and a section stored in 10% buffered formalin for histomorphometry whilst the rest was frozen for later lipid extraction. Hepatic lipid content was determined using the solvent (chloroform and methanol) extraction method as described by Bligh and Dyer (1959). The formalin preserved liver samples were processed for histology, stained with haematoxylin and eosin (HE) to assess hepatocellular changes and Masson’s trichrome (MT) to assess fibrosis according to standard protocols as described by Bancroft and Gamble (2008). The hepatic lipid content was similar across the treatment groups in the rats (2.1-3.3%, p>0.05, ANOVA). The livers of the rats that had fructose either as neonates and/or in the growing period had marked inflammation (3/3 vs 0/3 NAS score, p= 0.0015, Kruskal Wallis) and significant fibrosis (7.5 vs 1.0%, p<0.0001, ANOVA) with sinusoidal dilatation which were attenuated by curcumin. Curcumin administration to pups attenuated the fructose-induced hepatic inflammation and fibrosis in livers of adolescent male rats and thus is a potential for prevention of non-alcoholic steatohepatitis.



Where applicable, experiments conform with Society ethical requirements.

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