Bixin attenuates carbon tetrachloride induced oxidative stress, inflammation and fibrosis in kidney by regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-β1/Smad3 pathway

• DOI: 10.1016/j.intimp.2020.107117
• Publication Date: 2020-11-06T08:34:28Z
• Authors: Jie-Qiong Ma; Yu-Jia Zhang; Zhi-Kai Tian; Chan-Min Liu
• Keywords: Male; 0301 basic medicine; Mice, Inbred ICR; NF-E2-Related Factor 2; Anti-Inflammatory Agents; Kidney; Carotenoids; Fibrosis; Antioxidants; 3. Good health; PPAR gamma; Toll-Like Receptor 4; Transforming Growth Factor beta1; Disease Models, Animal; Oxidative Stress; 03 medical and health sciences; Myeloid Differentiation Factor 88; Animals; Kidney Diseases; Smad3 Protein; Inflammation Mediators; Carbon Tetrachloride; Signal Transduction

Bixin, an natural carotenoid extracted from the seeds of the Bixa orellana has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of Bixin on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. Our results showed that Bixin improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. Bixin ameliorated CCl4-induced inflammation in kidneys by reducing the levels of TNF-α and IL-1β. Bixin suppressed oxidative stress by decreasing the MDA level and increasing the activation of SOD, CAT and GPx. Furthermore, Bixin increased the levels of PPAR-γ, NQO1, HO-1 and the nuclear translocation of Nrf2 in the kidneys of mice. Bixin supplementation inhibited the activation of TLR4, MyD88, NF-κB, TGF-β and Smad3. Thus, this study demonstrated that Bixin possesses anti-oxidant, anti-inflammatory and anti-fibrosis properties through regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-β1/Smad3 pathways.