ABSTRACT
Background: Cyclophosphamide (CYP) is a chemotherapy drug widely used in the treatment of several types of cancers and autoimmune disorders. Unfortunately, it causes severe side effects on many organs due to its oxidative stress effect. Objective: The present study aims to tentatively identify the phytochemical constituents of orange fruit (Citrus sinensis) peel extract (OFPE) and elucidate the chemopreventive effects of OFPE on CYP drug induced organ toxicity. Methods: The high performance liquid chromatography coupled with mass spectroscopy (HPLC-MS/MS) technique was used to identify the compounds. Thirty-five male rats were divided into five groups (GP; n = 7): GP1: normal control, GP2: OFPE 0.5 only, GP3: CYP-only, GP4: OFPE 0.25 + CYP, and GP5: OFPE 0.5 + CYP. Results: Twenty-nine compounds of polyphenolic nature, mainly flavonoids, anthocyanidins, phenolic acids and limonoids were characterized by HPLC-MS/MS analysis. Among these compounds, naringin, hesperidin, diosmin, rutin, neohesperidin and limonin were the predominant compounds in the examined extract. Serum cellular markers were found to be decreased significantly upon treatment with OFPE (especially high dose). Also, a significant prophylactic effect against liver, kidney, and heart injuries induced by CYP via decreasing inflammation (serum TNF-α, IL-1ß & IL-6) and lipid peroxidation (MDA) was also revealed. Also, an increase in antioxidant levels (serum TAO, and cellular GSH & CAT in tissue homogenates) confirmed the protective efficacy of OFPE against CYP toxicity. Conclusions: The present study reveals some chemopreventive properties and beneficial effects of OFPE on CYP-induced organ toxicity via its antioxidant status and immunoregulatory activities.
Subject(s)
Antineoplastic Agents, Alkylating/toxicity , Citrus sinensis/chemistry , Cyclophosphamide/toxicity , Plant Extracts/pharmacology , Animals , Body Weight/drug effects , Cytokines/blood , Heart/drug effects , Inflammation , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Male , Myocardium/metabolism , Organ Size/drug effects , Oxidative Stress , Plant Extracts/chemistry , Plant Extracts/toxicity , Rats , Rats, WistarABSTRACT
Non-avian reptiles are good models to investigate structural and developmental differences between amniotes. Investigations of craniofacial development in a complete series of embryos from oviposition up to hatching are still relatively rare. Consideration of a complete series can reveal developmental events that were previously missed, and thus correct or confirm theories about developmental events. The Egyptian Sand snake, Psammophis sibilans, has been a key species in descriptions of the snake skull development. However, published work was based on a limited sample of specimens collected from the wild. Here, we supplement previous descriptions with an illustrated account of skull development in P. sibilans based on a staged series of embryos and histological sections. Our findings largely agree with those of previous authors, although we record differences in developmental timing, confirming the presence of an egg tooth in this species. We add further observations on the enigmatic fenestra X, showing that it closes rather than merging with the prootic notch. Our observations revealed the likely contribution of the tectum posterius to the occipital roof, the presence of an internal carotid foramen (possibly transitory or variable), and the formation of the initial laterosphenoid pillar.
