Protective Role of Ginger against Metformin Induced Alteration in Bcl2 Expression in the Spleen of Normoglycemic Albino Rat

Abstract

Background: The spleen is the largest and most essential organ in lymphoid system for the immunological reactions in the blood. Apoptosis can be defined as a programmed cell death in tissues. The B-cell leukemia/lymphoma-2 (Bcl-2) families are apoptosis regulators. Metformin is a safe drug that can lower blood glucose level, and may be used in non-diabetic patients with polycystic ovarian syndromeor with impaired glucose tolerance. Ginger is a member of ginger family. It has been used in India as a treatment for headache and common cold. It is known as an anti-oxidant agent. Aim of the work: This study has been designed to evaluate the possible pathological effect of metformin on spleen in normoglycemic rats, it's possible effect on Bcl2 expression, and the potential protective role of ginger. Material and methods: Thirty adult male albino rats (200-250gm) were obtained from AL-Nile Experimental Animal Center, Mansoura, Egypt. The animals were divided randomly into 3groups 10 rats each; Control, metformin treated group (200mg/kg orally for 1 month), and metformin-ginger group (200mg/kg /day metformin + 300 mg/kg/day ginger for 1 month). Rats in each group were weighted and sacrificed at the end of the experiment, spleen were dissected. The specimens were used for paraffin sections, stained with hematoxylin-eosin (HE), Masson's trichrome and Bcl2 immunohistochemistry. Results: Sections of ME treated group showed distorted splenic contour, degenerated cells with vacuolated cytoplasm and pyknoticnuclei. Masson trichrome stained sections revealed massive fibrosis in white pulp, red pulp and among cellular cords. The spleen treated with (ME+G) showed normal architecture without distortion, well defined white pulp, red pulp and splenic sinuses. The cellular cord showed lymphocytes and macrophages. Masson trichrome stained sections of the spleen showed minimal fibrosis among cellular cords. The treated group with metformin (ME), showed reduction of Bcl2 expression in all zones. While, the metformin-ginger (ME+G) treated group showed extensive expression in germinal center, mantle layer and marginal zone. Conclusion: From this study, it be concluded that metformin like any other drug may have beneficial curative properties in some medical conditions, however it should used be with caution to avoid its hazardous effect especially in the spleen which is the most vital organ in lymphatic and immune system. Also, ginger is a natural herbal agent could protect from hazardous side effect of metformin.