Combination of Vitamin C and Curcumin Safeguards Against Methotrexate-Induced Acute Liver Injury in Mice by Synergistic Antioxidant Effects

Abstract

Methotrexate (MTX), an antineoplastic and immunosuppressive drug, widely used in the treatment of different types of cancers and the management of chronic inflammatory diseases. However, its use is associated with hepatotoxicity. Vitamin C (VC) and curcumin (CUR) exhibit anti-inflammatory and antioxidant effects. Thus, we aimed to investigate the potential hepatoprotective effects of VC and CUR pretreatment alone and in combination against MTX-induced hepatotoxicity. Albino mice were randomly divided into 7 groups: the control group, which received only normal saline; MTX group; VC group, pretreated with VC (100 or 200 mg/kg/day orally) for 10 days; CUR group, pretreated with CUR (10 or 20 mg/kg/day orally); and combination group, which received VC (100 mg/kg) and CUR (10 mg/kg). MTX was administered (20 mg/kg, intraperitoneally) to all the groups on the tenth day to induce hepatotoxicity. Forty eight hours after MTX administration, the mice were anesthetized. Blood samples were collected, the liver was removed for biochemical analysis, and a part of the tissue was preserved in formalin for histopathological analysis. The results indicated that pretreatment with a combination of VC and CUR induced a more significant decrease in the serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactic dehydrogenase and a significant increase in the tissue level of superoxide dismutase and glutathione; furthermore, it induced a significant decrease in malondialdehyde levels and improvement in histopathological changes in the liver tissues, confirming the potential hepatoprotective effects of the combination therapy on MTX-induced liver injury. To conclude, MTX-induced hepatotoxicity is mediated by induction of oxidative stress as evident by increased lipid peroxidation and reduction of antioxidant enzyme activity. Pretreatment with VC, CUR or their combination reduces the MTX-induced hepatotoxicity by antioxidant and anti-inflammatory effects. However, the combined effect of VC and CUR provided a synergistic hepatoprotective effect that surpasses pretreatment with CUR alone but seems to be similar to that of VC 200 mg/kg/day. Therefore, VC and CUR combination or a large dose of VC could be effective against MTX-induced hepatotoxicity. In this regard, further studies are warranted to confirm the combined hepatoprotective effect of VC and CUR against MTX-induced hepatotoxicity.

Triptolide and l-ascorbate palmitate co-loaded micelles for combination therapy of rheumatoid arthritis and side effect attenuation

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Encephalartos villosus Lem. Displays a Strong In Vivo and In Vitro Antifungal Potential against Candida glabrata Clinical Isolates

“…Additionally, Oliveira et al elucidated the effectiveness of Myracrodruon urundeuva plant extract against Candida sp. [ 20 ]. However, most of the conducted research focused on C. albicans , and little attention has been given to C. glabrata.…”

“…Samples of kidney tissues were collected from each rat, then fixed with formalin (10%) for 72 h to be histopathologically examined. The tissue was dehydrated, embedded in paraffin wax, sectioned (3 μm), and stained with hematoxylin and eosin (H&E) [ 20 ] and Masson’s trichrome stains. Finally, photos were captured using a digital camera [ 13 , 14 ].…”

Anti-Biofilm and Antibacterial Activities of Cycas media R. Br Secondary Metabolites: In Silico, In Vitro, and In Vivo Approaches

“…Hematoxylin and eosin (H&E), in addition to Masson’s trichrome staining, were performed on the liver and spleen tissues and were preserved in 10% formalin of the different tested groups. Then, photos were obtained using a digital camera to investigate the in vivo antibacterial potential of SOTE [ 33 , 34 ].…”