Rosmarinic acid protects against cyclophosphamide-induced hepatotoxicity via inhibition of oxidative stress, inflammation, and apoptosis and upregulation of Nrf2 in mice.

Publisher: Springer Netherlands Country of Publication: Netherlands NLM ID: 101193653 Publication Model: Electronic Cited Medium: Internet ISSN: 1567-2387 (Electronic) Linking ISSN: 15672379 NLM ISO Abbreviation: J Mol Histol Subsets: MEDLINE

Publication: Dordrecht, The Netherlands : Springer Netherlands
Original Publication: Dordrecht, The Netherlands : Kluwer Academic Publishers, 2004-

Rosmarinic Acid* ; Depsides*/pharmacology ; NF-E2-Related Factor 2*/metabolism ; Oxidative Stress*/drug effects ; Cyclophosphamide*/adverse effects ; Cyclophosphamide*/toxicity ; Cinnamates*/pharmacology ; Apoptosis*/drug effects ; Chemical and Drug Induced Liver Injury*/metabolism ; Chemical and Drug Induced Liver Injury*/prevention & control ; Chemical and Drug Induced Liver Injury*/drug therapy ; Chemical and Drug Induced Liver Injury*/pathology; Animals ; Mice ; Male ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation/drug therapy ; Liver/drug effects ; Liver/pathology ; Liver/metabolism ; Antioxidants/pharmacology ; Up-Regulation/drug effects ; Protective Agents/pharmacology

Cyclophosphamide (CP) is widely used in chemotherapy to treat various types of cancer. However, it is toxic to the liver and other organs. Rosmarinic acid (RA) possesses anti-inflammatory, antioxidant, and cytoprotective properties. This study investigated the protective effects of RA against CP-induced liver injury in mice. Mice were treated with RA (25, 50, and 100 mg/kg) for 15 days and followed by a single injection of CP on day 16th. CP injection resulted in an elevation in serum AST, ALT, and ALP, along with multiple histopathological alterations in the liver. CP also induced increased levels of MDA and NO, associated with declined GSH, SOD and CAT. RA pretreatment prevented liver injury, alleviated the enhanced levels of MDA and NO, and restored antioxidants defenses, hence avoiding the oxidative injury in the liver. Moreover, RA pretreatment attenuated NF-κB p65 and proinflammatory cytokines levels. Liver of CP-injected mice also showed a decrease in Bcl2, accompanied with elevated BAX and caspase-3 expression, an effect that RA pretreatment alleviated. In addition, pretreatment of CP-administrated mice with RA restored the Nrf2 expression in the liver. Taken together, this study suggests a potential application value of RA in preventing CP hepatotoxicity and sheds light on the possible mechanism.
Competing Interests: Declarations. Competing interest: The author declares no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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Keywords: Cyclophosphamide; Inflammation; Liver injury; Oxidative stress; Rosmarinic acid

MQE6XG29YI (Rosmarinic Acid)
0 (Depsides)
0 (NF-E2-Related Factor 2)
8N3DW7272P (Cyclophosphamide)
0 (Cinnamates)
0 (Antioxidants)
0 (Nfe2l2 protein, mouse)
0 (Protective Agents)

Date Created: 20241220 Date Completed: 20241220 Latest Revision: 20241220

20241220

10.1007/s10735-024-10290-6

39702535