Prophylactic and curative effects of Carica papaya Linn. pulp extract against carbon tetrachloride-induced hepatotoxicity in male rats

Environ Sci Pollut Res Int. 2023 Feb;30(10):27815-27832. doi: 10.1007/s11356-022-24083-5. Epub 2022 Nov 17.

Abstract

Several chemicals and medications induce cellular damage in various organs of the body by activating reactive substances' metabolism leading to various pathological conditions including liver disease. In this study, we evaluated the prophylactic and curative effects of Carica papaya Linn. pulp water extract (PE) against CCl4-induced rat hepatotoxicity. Five groups of rats were created, control, PE, CCl4, (PE-CCl4): The rats were administered with PE pre and during CCl4 injection, and (PE-CCl4-PE): The rats were administered with PE pre, during, and after CCl4. The markers of oxidative stress ("OS": oxidant and antioxidants), inflammation [nuclear factor-κB, tumor necrosis factor-α, and interleukin-6], fibrosis [transforming growth factor-β], and apoptosis [tumor suppressor gene (p53)] were evaluated. Additionally, liver functions, liver histology, and kidney functions were measured. Also, PE characterization was studied. The results showed that PE, in vitro, has a high antioxidant capacity because of the existence of phenolics, flavonoids, tannins, terpenoids, and minerals. Otherwise, the PE administration [groups (PE-CCl4) and (PE-CCl4-PE)] exhibited its prophylactic and therapeutic role versus the hepatotoxicity induced by CCl4 where PE treatment improved liver functions, liver histopathology, and renal functions by decreasing oxidative stress, inflammation, fibrosis, and apoptosis induced by CCl4. Our study elucidated that PE contains high amounts of phenolics, flavonoids, tannins, terpenoids, and ascorbic acid. So, PE exerted significant prophylactic and curative effects against hepatotoxicity induced by CCl4. These were done by enhancing the markers of antioxidants and drug-metabolizing enzymes with reductions in lipid peroxidation, inflammation, fibrosis, and apoptosis. PE administration for healthful rats for 12 weeks had no negative impacts. Consequently, PE is a promising agent for the prohibition and therapy of the toxicity caused by xenobiotics.

Keywords: Apoptosis; CCl4; Carica papaya Linn. pulp extract; Fibrosis; Inflammation; Oxidative stress; Rat liver injury.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Carbon Tetrachloride
  • Carica* / metabolism
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Fibrosis
  • Flavonoids / pharmacology
  • Inflammation / metabolism
  • Lipid Peroxidation
  • Liver
  • Male
  • Oxidative Stress
  • Plant Extracts / chemistry
  • Rats
  • Tannins / pharmacology

Substances

  • Carbon Tetrachloride
  • Antioxidants
  • Plant Extracts
  • Tannins
  • Flavonoids