Evaluation of the citral action in lipopolysaccharide-induced systemic inflammation in obese mice with a high-fat diet

Author(s)

Maycon Tavares Emilio Silva

• Document type: Master's Dissertation
• Press: Botucatu. 2020-03-20.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2020-02-19
• Advisor: Clélia Akiko Hiruma Lima; Lúcia Regina Machado da Rocha; Luiz Guilherme de Siqueira Branco

Abstract

Obesity is considered a public health problem, which has growing in many countries around the world. Ingestion of a rich fat diet leads to a progressive increase in adipose tissue and triggers changes in immune system modulation, increasing the concentration of systemic biomarkers such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and leptin. The low-grade chronic inflammation associated with obesity increases the susceptibility to infections, which results in changes in host homeostasis capable of promoting effector responses in order to protect it from the pathogen. One of the main responses triggered during the systemic inflammation is the body temperature variation, defined as a controlled increase in Tc due to the production of peripheral and central inflammatory mediators such as systemically produced IL-1β, IL-6, TNF-α. In order to minimize the harmful effects of systemic inflammation, drugs such as non-steroidal anti-inflammatories drugs (NSAIDs) are used in current therapy, but the indiscriminate and chronic use can cause significant harm to users, such as the formation of gastric ulcers. This project presents data on the action of citral, a monoterpene found in different essential oils of medicinal plants with anti-inflammatory action, antipyretic and antihyperlipidemic reported in the literature. For this, we used male Swiss mice, fed for 12 weeks with standard diet (SD) and high-fat diet (HFD). We evaluated the action of citral (25, 100 and 300 mg/kg) on LPS-induced systemic inflammation. After LPS-injetion intraperitoneal i.p., we obtained Tc data and collected samples of serum and gastric mucosa for biochemical and molecular dosages. Our results confirm the induction of obesity with HFD, with the significant increase in body weight and adipose tissue (epididymal, retroperitoneal and visceral) and organs (liver, spleen and kidneys) when compared with SD mice. Citral showed dose dependent action on body temperature profile in animals SD and HFD. The thermal index of citral-treated animals (300 mg/kg) was significantly lower in HFD-treated obese animals when compared to SD animals, indicating an effective cryogenic action of this essential oil in the obese group. Citral treatment reduced the peripheral inflammatory signaling of TNF-α in SD and HFD animals and reduced the plasma leptin concentration in HFD animals after LPS challenge by 90 minutes. Also, the citral reduced the concentration of IL-6 levels in the hypothalamus of obese mice. We also characterize renal (urea and creatinine) and hepatic (AST, ALT, alkaline phosphatase and γ-GT) biochemical parameters of animals exposed to LPS and treated with citral and ibuprofen (IBU), a classic NSAIDs. Biochemical parameters indicate that the HFD diet reduced the alkaline phosphatase levels of obese animals compared to SD animals. Citral (100 mg/kg) also reduced the alkaline phosphatase levels of the SD animals and raised the ALT levels in the HFD animals compared to their respective control animals (Tween 80 + Saline). In the evaluation of gastric mucosa of SD and HFD animals treated with citral or IBU it was possible to characterize that there was no change in the levels of markers for oxidative stress (malondialdehyde - MDA and reduced glutathione - GSH) and local inflammation (myeloperoxidase - MPO). The results obtained so far demonstrate that the citral acts to effectively reduce body temperature during systemic inflammation, with a different action profile in HFD animals when compared to SD. (AU)

• FAPESP's process: 18/10935-0 - Evaluation of action citral on lipopolysaccharide-induced fever in obese mice with high-fat diet
• Grantee: Maycon Tavares Emílio Silva
• Support Opportunities: Scholarships in Brazil - Master