Cellular genetic expression of purinergic receptors in different organs of male rats injected with cyclophosphoamide
الباحث الأول:
Hydar Muhsin khalfa
الباحثين الآخرين:
Haider lateef al-msaid, Ali hassan abood, Murtadha abdulkadir naji, and Surar khalil Hussein
المجلة:
AIP Conference Proceedings
تاريخ النشر:
None
مختصر البحث:
Cyclophosphamide is a common anticancer drug that belongs to the nitrogen mustard group of alkylating agents, their acts by adding an alkyl group to DNA. Due to this cytotoxic property it is used extensively in a variety of carcinomas singly or in c…
Cyclophosphamide is a common anticancer drug that belongs to the nitrogen mustard group of alkylating agents, their acts by adding an alkyl group to DNA. Due to this cytotoxic property it is used extensively in a variety of carcinomas singly or in combination with other drugs to treat a variety of cancers. Purinergic nucleotides targets a group of receptors known as purinergic receptors, which fall into two classes P2Y and P2X receptors, the P2Y receptors are membrane bound G protein coupled receptors. Purinergic signaling has been shown to play a significant role in the regulation of proliferation in many animal and human tissues. Therefore, the present study was conducted to compare and correlate histomorphological alterations in different anatomical sites of adult wistar albino rat induced by a gradual increase in cyclophosphoamide dose administered intraperitoneally and subcutaneously and correlate the effect of cyclophosphamide with purinergic receptor gene expression. The aim of this study is to examine the effect of cyclophosphoamide on histological and cellular changes when administered in two different methods as well as examine purinergic receptor gene expression post cyclophosphoamide injection. Material and methods: Laboratory wistar albino rats were injected with different bolus doses of cyclophosphoamide intraperitoneally and subcutaneously and were sacrificed after seven days . liver, kidney , testes and subcutaneous injection sites were examined histologically and compared to control animals. Purinergic receptors P2Y1, P2Y2 and P2Y4 Gene expression changes were assessed using Quantitative reverse transcriptase polymerase chain reaction. Results: histological examination of all tissues in both groups shows gradual cytotoxic effect of cyclophosphoamide reaching extreme histological damage with increased bolus dose. Tissue damage included hemorrhaging and lymphocytic collection. Gene fold change of purinergic receptors showed an increase in genetic expression of P2Y1, P2Y2 and P2Y4 receptors in all examined site which indicates ectopic overexpression of purinergic receptors with increases cyclophosphamide specific dose. Increased gene fold change is an indication to cellular response to inflammatory histological damage caused by cyclophosphamide administration. The results of this study show that purinergic receptors are highly involved in cellular damage restoration through ectopic gene overexpression in tissues damaged by cyclophosphamide. Conclusion: This study concludes that cyclophosphoamide has a strong cytotoxic effect on certain organs if injected at a high dose intraperitoneally of subcutaneously. However histological damage is more prominent in intraperitoneal injected animals compared to subcutaneously injected animals. Cytotoxic effect and histological damage is confirmed by the gradual increase in purinergic receptors gene expression in both intraperitoneally and subcutaneously injected animals indicating an inflammatory response by increased gene fold change post administration of cyclophosphoamide and with gradual increase in cyclophosphoamide dose. It is a safer and less damaging to administer cyclophosphoamide subcutaneously.
