Garden Croton mitigates Carmustine-provoked Histopathological and Immunohistochemical Aspects in Liver, Kidney and Testis and UPLC-QTOF- MS/MS Identification of its Bioactive Compounds

Abd-Alla, Howaida I.; Sweelam, Heba-tollah M.; Fahmy, Maha A.; Omara, Enayat A.; Maamoun, Maii A.I.

doi:10.21608/ejchem.2024.327137.10612

Garden Croton mitigates Carmustine-provoked Histopathological and Immunohistochemical Aspects in Liver, Kidney and Testis and UPLC-QTOF- MS/MS Identification of its Bioactive Compounds

Document Type : Original Article

Authors

¹ Chemistry of Natural Compounds Department, National Research Centre, 12622, Dokki-Giza, Egypt.

² Department of Genetics and Cytology, National Research Centre, 12622, Dokki-Giza, Egypt

³ Department of Pathology, National Research Centre, 12622, Dokki-Giza, Egypt.

⁴ Pharmacognosy Department, National Research Centre, 12622, Dokki-Giza, Egypt.

10.21608/ejchem.2024.327137.10612

Abstract

Carmustine (BCNU) is a chemotherapeutic drug known to induce different toxicity on various organs. Evaluation of the histological, immunohistochemical changes in the liver, kidney and testis of mature Swiss male mice after BCNU was carried out and the possible role of ethyl acetate extract of Codiaeum variegatum aerial parts (CvAp-EA) supplementation to mitigate BCNU-provoked histopathological and immunohistochemical aspects in the three organs was explored. Quantitative determination of total flavonoids and phenolics content were carried out. HR-UPLC-qTOF-MS/MS analysis was performed in two ionization modes to detect the plant metabolites comprehensively. Thirty Swiss male mice weighted 25 g were categorized into five groups, (ten mice each group). Group I: Negative control (30 % ethanol). Group II: Positive control (i.p injected with a dose of BCNU, 33 mg/kg b.wt.). Group III: control orally administrated CvAp-EA at 500 mg/kg, four days. Groups IV-VI: rat received repeated oral gavages treatment with extract (100, 300 and 500 mg/kg b.wt.) for four days and a dose of BCNU (33 mg/kg b.wt.). The group treated with BCNU was characterized by some histopathological changes as disorganization of spermatogonial cell layers and deformation of Leydig cells. CvAp-EA co-treatment alleviated these histopathological and immunohistochemical changes. CvAp-EA improved the testicular histology and decreased p53 positive immune-reaction in BCNU administered mice. In conclusion CvAp-EA co-treatment successfully mitigated the alterations induced by BCNU toxicity in the three organs. Treatment with CvAp-EA was found to almost restore the normal histopathological architecture of organs of BCNU-induced toxicity mice. Glomerular size and damaged area showed ameliorative effect after treatment with CvAp-EA. Results revealed the tentative identification of 93 compounds belonging to eight phytochemical classes. Total flavonoids were 16.24 ±1.12 mg quercetin equivalent/g dry matter (D.W.) and the total phenolics were 14.53 ±1.89 mg gallic acid equivalent/g D. W. extract of CvAp-EA. The recorded bioactivity of CvAp-EA could be attributed to the major compounds of flavonoids/glycosides, phenolic compounds, fatty acids, and nitrogenous compounds or synergy between these major and minor constituents (such as carboxylic acids, coumarins, sugars, and triterpenoids) which can act by different mechanisms The current research identified for the first time the phytochemicals of Codiaeum species using advanced UPLC-qTOF-MS/MS analysis and the study is the first to demonstrate that CvAp-EA can alleviate histopathological and immunohistochemical changes exerted by BCNU toxicity.

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