Contents lists available at ScienceDirect Experimental Cell Research journal homepage: www.elsevier.com/locate/yexcr Sericin improves heart and liver mitochondrial architecture in hypercholesterolaemic rats and maintains pancreatic and adrenal cell biosynthesis Sumate Ampawong a , Duangnate Isarangkul b , Pornanong Aramwit c, ⁎ a Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand b Department of Microbiology, Faculty of Science, Mahidol University, 272, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand c Bioactive Resources for Innovative Clinical Applications Research Unit and Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, PhayaThai Road, Phatumwan, Bangkok 10330, Thailand ARTICLE INFO Keywords: Aquaporin-1 Hypercholesterolaemia Lipase Mitochondria Sericin Superoxide dismutase Tubulin-β ABSTRACT Hypercholesterolaemia is well known to be associated with mitochondrial dysfunction, subsequently leading to multiple organ failure. Similar to other natural products, sericin is a candidate for adjunctive therapy in hyperlipidaemic conditions. However, the cholesterol-lowering mechanisms of sericin are multifactorial and controversial. Here, a high-cholesterol-fed rat model with or without sericin treatment was established using a dosage of 1000 mg/kg/day for 30 days. Blood lipid profiles, oxidative stress markers (superoxide dismutase, SOD; malondialdehyde, MDA; nuclear factor erythroid 2-related factor, Nrf-2), dysmorphic mitochondria in relation to fission (dynamin-related protein-1; Drp-1) and fusion (guanosine triphosphatase mutated in dominant optic atrophy; OPA-1) markers and biosynthetic markers (aquaporin, AQP-1; tubulin-4β, Tb4B) in the pancreas and adrenal gland were evaluated. The results showed that sericin reduced blood cholesterol and increased high-density lipoprotein (HDL) by acting against oxidative stress. Hypocholesterolaemic and antioxidant conditions further preserved heart and liver mitochondrial architecture; however, this protection was not exhibited in the kidney, where a high level of renal mitophagy, indicating by LC-3 up-regulation, was presented. The steps of ultrastructural alteration of mitochondria from degenerative changes to necrosis were also demonstrated. Sericin also conserved AQP-1 and Tb4B levels in the exocrine pancreatic acinar cells and zona glomerulosa cells, which were positively correlated with serum lipase, HDL, antioxidative markers and mitochondrial integrity. The present study revealed that sericin not only has antioxidant capacity but also balances pancreatic and adrenal cell biosynthesis, especially lipase activity, which may have played an important role in improving lipid dysregulation in the hypercholesterolaemic rat model, leading to the reduction of dysmorphic mitochondria, particularly in the heart and liver. 1. Introduction Mitochondrial dysfunction has been claimed to be an important phenomenon in dietary-induced hypercholesterolaemia, leading to organ insufficiency or failure, particularly in the heart, liver and kidney [1–3]. Our recent study showed that short-term sericin consumption alleviates mitochondrial dysfunction in the heart and liver due to its antioxidative property, which further lowered the blood cholesterol level without hypoglycaemic effect in a hypercholesterolaemic and diabetic rat model [4]. Our previous study also demonstrated that sericin reduces the severity of microvesicular steatosis in the liver. Studies of the cholesterol-lowering mechanism of sericin have mainly focused on the gastroduodenal level, for example, absorption site effects and intracellular tracking [5,6]. However, the roles of sericin during the events after cholesterol absorption, such as its entry into the blood circulation, a high persistence of blood cholesterol and then cellular deposition, remain controversial. Catabolic enzymes and hormones are important for regulating the blood cholesterol level in association with accelerating internal meta- bolism. It is well understood that lipase, in both serum and tissue, promotes lipolysis, reduces blood cholesterol and triglyceride and maintains a normal blood lipid profile [7–9]. Taking these findings together, glucocorticoids are well described to affect serum lipids and induce hyperlipidaemia [10–12] in relation to the increased metabolic availability of fatty acids. Dysregulation of their synthesis leads to many features of metabolic syndrome, disordered lipid metabolism, hepatic http://dx.doi.org/10.1016/j.yexcr.2017.07.001 Received 16 February 2017; Received in revised form 17 June 2017; Accepted 1 July 2017 ⁎ Corresponding author. E-mail addresses: am_sumate@hotmail.com (S. Ampawong), duangnate.int@mahidol.ac.th (D. Isarangkul), aramwit@gmail.com (P. Aramwit). Experimental Cell Research xxx (xxxx) xxx–xxx 0014-4827/ © 2017 Elsevier Inc. All rights reserved. Please cite this article as: Ampawong, S., Experimental Cell Research (2017), http://dx.doi.org/10.1016/j.yexcr.2017.07.001