Hepatoprotective effect of limonene against chronic immobilization induced liver damage in rats

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ORIGINAL ARTICLE

Hepatoprotective effect of limonene against chronic immobilization induced liver damage in rats Rahim Amini 1 & Masoumeh Asle-Rousta 2

&

Safieh Aghazadeh 3

Received: 17 February 2020 / Accepted: 28 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Prolonged immobilization may impair the physiological functions of various organs of the body, including the liver, brain, and heart. In this study, we investigated the hepatoprotective effect of limonene (a monoterpene) in male rats exposed to chronic immobilization. Rats were exposed to immobilization stress (6 h/21 days) and received limonene (10 mg/kg, oral gavage) during this period. Chronic immobilization increased the levels of liver enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in serum. Increased levels of malondialdehyde and decreased glutathione content were also observed in the liver tissue of immobilized rats. Expression of TNF-α, IL-1β, IL-6, and NF-κB mRNA was increased, and infiltrated cells were also observed in the liver parenchyma in rats exposed to chronic immobilization. Limonene prevented all these changes in immobilized rats. These results suggest that limonene, due to its antioxidant and anti-inflammatory effects, rescues the liver from damages caused by chronic immobilization. Keywords Limonene . Oxidative stress . Inflammation . Liver enzymes . Hepatoprotection . Immobilization

Introduction Immobilization is one of the types of stress that in the long term can lead to various diseases by disrupting physiological homeostasis. For example, immobilization stress alters the metabolism and detoxification of lipids in the liver (Paré and Glavin 1986; Ha et al. 2003). Immobilization stimulates the hypothalamic-pituitary-adrenal axis and consequently increases the corticosterone concentration in the blood. Oxidative stress and inflammation in the liver are the results of immobilization stress. Immobilization reduces vitamin C, decreases oxygen radical absorbance capacity, causes Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01915-0) contains supplementary material, which is available to authorized users. * Masoumeh Asle-Rousta [email protected] 1

Biology Research Center, Zanjan Branch, Islamic Azad University, Zanjan, Iran

2

Department of Physiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran

3

Department of Biochemistry, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

mitochondrial dysfunction, and stimulates the production of malondialdehyde in the liver. Under immobilized stress conditions, tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-light-chain-activated B cells (NF-κB) mRNA expression is increased in the liver, and eventually, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated in the serum. Inflammatory cellular infiltration, vacuolization of hepatocytes, and apoptosis of these cells are also the results of immobi