The adaptogenic anti-ageing potential of resveratrol against heat stress-mediated liver injury in aged rats: Role of HSP70 and NF-kB signalling

J Therm Biol. 2019 Jul:83:8-21. doi: 10.1016/j.jtherbio.2019.04.012. Epub 2019 May 1.

Abstract

Heat stress (HS) is a major international problem which has attracted a considerable attention due to its oxidative tissue effects and high morbidity and mortality rates, especially among elderly people. Discovering an effective antioxidant is pivotal for overcoming HS-induced injury. Therefore, the aim of this study was to estimate the hepatic protective effects of orally supplemented resveratrol (RES) against HS-mediated liver injury in young and old male Wistar albino rats. Compared to control rats, RES administered orally at a dose of 20 mg/kg BW for 21 successive days efficiently ameliorated HS-induced oxidative damage by significantly increasing (P ≤ 0.05) the level of reduced glutathione and glutathione peroxidase, and decreasing the levels of malondialdehyde and TNF-α in hepatic tissue of both young and aged rats. However, level of NF-κB was downregulated significantly in aged rats rather than young rats. Moreover, RES significantly decreased (P ≤ 0.05) the serum levels of aspartate transaminase and alkaline phosphatase in both ages of rats compared to their corresponding HS-stressed rats. Furthermore, RES upregulated the immunohistochemical expression of caspase 3 and heat shock protein 70 in young and aged rats, however it was more pronounced in young one. In addition, RES administration moderately normalized (P ≤ 0.0001) the harmful effects of HS on the hepatic architecture of both young and aged rats. In conclusion, this study reveals for the first time that RES exerts promising hepato-ameliorative effects against HS-induced oxidative stress in the young and aged rats via its antioxidant, anti-inflammatory, and anti-apoptotic effect, as well as via its inhibitory effect against the NF-κB signalling in a cellular system.

Keywords: Ageing; HSP70; Heat stress; NF-kB; Resveratrol.

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis
  • Aspartate Aminotransferases / blood
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat Stress Disorders / complications*
  • Liver / drug effects
  • Liver / growth & development
  • Liver / metabolism
  • Liver Diseases / drug therapy*
  • Liver Diseases / etiology
  • Liver Diseases / metabolism
  • Male
  • NF-kappa B / metabolism*
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Resveratrol / administration & dosage
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • HSP70 Heat-Shock Proteins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Aspartate Aminotransferases
  • Alkaline Phosphatase
  • Resveratrol