Up-Regulation of Bcl-2/ Bax Apoptotic Genes in Cytarabine – Induced Toxicity and Intervention of Melatonin in Female Endometrial Tissue

Chemotherapy remains a cornerstone in cancer treatment, yet its cytotoxic effects on normal tissues, including the female endometrium, present significant challenges. Cytarabine, a nucleoside analog widely used in hematological malignancies, exerts its anticancer effect through inhibition of DNA synthesis, but also induces apoptosis in normal cells. Apoptosis, a programmed cell death mechanism, is regulated by a delicate balance between pro-apoptotic (BAX) and anti-apoptotic (BCL-2) genes. Disruption of this balance can lead to tissue damage and compromise organs functions. Methods used to achieve these objectives included the isolation of endometrial tissue samples from experimental animal models (female wistar rat) treated with cytarabine alone and cytarabine co-treated with melatonin. The Estrogen, Gonadotropin releasing hormones and Follicle stimulating hormone levels from each group were estimated using ELISA method and expressed in ng/ml (Ojo, 2021). Endometrial homogenate were used to check the levels of Cyt c, CASP-9 and CASP-3 using ELISA method. Additionally, assays measuring Reactive oxygen species, Malondialdehyde and some activities such as Glutathione, Catalase, Superoxide Dismutase, Total antioxidant capacity, Glutathione peroxidase levels were also performed. The upregulation of BAX and downregulation of BCL-2 are indicative of apoptotic signaling pathways activated in response to cellular stress induced by cytarabine. Cytarabine administration has been shown to decrease estrogen levels in female wistar rats. This reduction in estrogen can disrupt the delicate hormonal balance critical for normal endometrial function and reproductive health. The study explores the potential ameliorative role of melatonin, a neurohormone with known antioxidant and anti-apoptotic properties. Melatonin has been suggested to mitigate oxidative stress and modulate apoptotic pathways in various tissues, its ability to scavenge reactive oxygen species (ROS) generated during cytarabine treatment, thereby reducing oxidative stress and subsequent tissue damage and to mitigate the decrease in estrogen levels induced by cytarabine thereby modulating estrogen levels, potentially counteracting the hormonal disruption caused by cytotoxic chemotherapy agents like cytarabine. The outcomes of this project enhance the understanding of cytarabine-induced toxicity in female reproductive tissues and elucidate mechanisms through which melatonin and its antioxidant properties may offer protective benefits.