Mechanisms of the anti-fibrotic impact of natural nutraceuticals in thioacetamide-induced hepatic fibrosis in obese rats

Document Type : Original Article

Authors

1 Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Buhouth St., Dokki, Giza, 12622, Egypt

2 Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

Abstract

Hepatic fibrosis is manifested by replacement of liver tissue by fibrosis, scar tissue, and regenerative nodules. The rational of the present attempt was to evaluate the anti-fibrotic outcome of lycopene and resveratrol against hepatic fibrosis induced in obese rats. Hepatic fibrosis model was carried out by thioacetamide (TAA) intraperitoneal administration (200 mg/kg b.wt) twice a week for 6 weeks. Obese model was created by feeding the rats with high fat diet (HFD) for 24 weeks. The lean control group, was administered saline intraperitoneally twice weekly for 6 weeks after feeding a standard chow diet for 24 weeks. The obese control group received intraperitoneal injection of saline twice a week for 6 weeks after feeding a high fat diet (HFD) for 24 weeks. Hepatic fibrosis lean group received intraperitoneal injection of TAA (200 mg/kg b.wt) twice a week for 6 weeks . Hepatic fibrosis obese group received intraperitoneal injection of TAA (200 mg/kg b.wt) twice a week for 6 consecutive weeks after feeding HFD for 24 weeks. Lycopene prophylactic group was given 20 mg/kg b.wt of lycopene by intragastric gavage tube daily for 6 weeks simultaneously with intraperitoneal injection with TAA (200mg/kg b.wt) before feeding HFD for 24 weeks. Resveratrol prophylactic group received 30 mg/kg b.wt of resveratrol intragastrically daily for 6 weeks simultaneously with intraperitoneal injection of TAA (200 mg/kg b.wt) before feeding HFD for 24 weeks. Lycopene therapeutic group was given 20 mg/kg b.wt of lycopene by gastric intubation with an oral gavage daily for 6 weeks after feeding HFD and TAA administration. Resveratrol therapeutic group received 30 mg/kg b.wt of resveratrol orally by gastric tube daily for 6 weeks after feeding HFD and TAA administration. The obtained findings indicated significant higher values of the anthropometric arametersincluding body weight, body length, WC, AC and BMI in obese control group than in lean control one. Also, serum glucose, insulin and IR values showed significant elevation in obese control group versus the lean control group. These results evidenced the success of obese model. The present results also highlighted that the severity of hepatic fibrosis in obese rats is superior than that in the lean counterparts as indicated by the significant increased values of ALT, AST, cholesterol, TG, LDL, leptin, TGF-β and fibronectin as well as the hepatic immune reaction for α-SMA, CD31 and CD34. The administration of lycopene or resveratrol in obese rats with hepatic fibrosis recovered the values of serum ALT, AST, cholesterol, TG, LDL, leptin, TGF-β and fibronectin significantly as well as ameliorated the severity of immune reaction for hepatic α-SMA, CD31 and CD34 markedly. The net results were greatly supported by the histomorphological hallmark of liver tissue sections of the different studied groups. Based on these outcomes, this research work explored the pharmacological activity of lycopene and resveratrol against hepatic fibrosis from a holistic perspective.The behind mechanism of this effect was closely related to the intervention of inflammatory pathway through their anti-oxidative properties.

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Volume 65, Issue 132 - Serial Number 13
Special Issue: Chemistry and Global Challenges (Part B)
December 2022
Pages 1567-1588
  • Receive Date: 22 April 2022
  • Revise Date: 19 March 2023
  • Accept Date: 03 July 2022