Medical Physiology

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Browsing Medical Physiology by browse.metadata.advisor "Bowles, Sandra"

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    In vitro assessment of aspalathin-enriched Rooibos (Aspalathus linearis) extract treatment in statin-induced hepatotoxicity
    (Stellenbosch : Stellenbosch University, 2019-04) Millar, Danielle Ann; Muller, Christo; Bowles, Sandra; Windvogel, Shantal; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Biomedical Sciences: Medical Physiology.
    ENGLISH ABSTRACT: Rooibos (Aspalathus linearis) has been shown to have various health benefits including antidiabetic, lipid-lowering, and hepatoprotective properties. Although anecdotally Rooibos consumption is regarded as safe, recently, two case studies have associated chronic consumption of Rooibos with conventional prescription medications, such as atorvastatin, with hepatotoxicity. The cholesterol-lowering drugs, statins, act by competitively inhibiting hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in cholesterol synthesis. Although rare in occurrence, statins are potentially hepatotoxic. The safety of the concurrent use of Rooibos and statins thus needs to be elucidated. This study aims to investigate the interaction between the potential hepatoprotective effects of Rooibos and statin-induced hepatotoxicity using an in vitro C3A liver cell model. C3A liver cells, in both normal and hyperlipidaemic conditions, were exposed to atorvastatin (ATV; 10 μM and 25 μM) and Afriplex GRT™ (green Rooibos extract; 0.01 mg/mL and 0.1 mg/mL) and a combination thereof. Pre-treatment with palmitate (500 μM) for 24 hours was used to induce a hyperlipidaemic condition in vitro. The effects of the co-treatment on cell viability, oxidative stress, apoptosis, mitochondrial integrity and cellular ROS production were assessed in a C3A liver cell culture model. In addition, 3D culture was used to produce C3A liver spheroids, and the effect of the treatments in a chronic culture was then assessed. GRT was not cytotoxic at any of the concentrations tested, whereas ATV showed time- and concentration-dependent cytotoxicity in C3A cells. A significant increase in ROS production was observed in C3A cells exposed to 25 μM ATV and palmitate (353.10% ± 262.70 vs. 1431.00% ± 504.2). Similar results were seen following ATV and GRT combination therapy (845.00% ± 589.60 vs. 1493.00% ± 278.4). Under hyperlipidaemic conditions, ATV induced significant increases in apoptosis (19.50% ± 3.56 vs. 52.83% ± 7.14) which was not ameliorated by GRT co-treatment (13.83% ± 2.79). The results of the 3D culture showed complementary results. Treatment with palmitate and ATV was toxic to the spheroids and treatment with GRT was unable to attenuate this toxicity. A decrease in cellular ATP was found in the ATV and ATV+GRT treated spheroids (1.45 AU/μm3 ± 1.00, and 3.79 AU/μm3 ± 2.32, respectively, vs control, 161.02 AU/μm3 ± 55.26) as well as decreased glucose utilisation calculated from the increased remaining glucose in the treatment media (91.83% and 94.68%, respectively, vs control,100%). The culmination of experiments showed that ATV was hepatotoxic. This effect was exacerbated by exposing the cells to palmitate intended to mimic a hyperlipidaemic condition. GRT co-treatment did not show any modulating effects on ATV-induced hepatotoxicity under the acute or chronic conditions tested.