Prophylactic Role of Glutathione and Granulocyte - Colony Stimulating Factor on 5-Fluorouracil Induced Myelotoxicity in Mice

Abstract

The protccliw: effect of glutatltioue (GSH) a11d granulocyte colony stimulating factor (G-CSF) 011 myelosuppression inducet! by 5-fluorouraci/ (5-FU) were compared in female mice. Tfte animals were divided into seven gro11ps. Group I (10 mice) received no treotment. group 2 (/0 mice) received GSH (800 mgl kg) by inrmperi10neal rotae in daily doses for rlre first 7 days thell left untreated for cmotfler 7 days, a11d ~JI'OIIJI J (10 mice) received G-CSF (250 11glkg) by subcuta11e0tts route in daily doses for the first 7 days tlt('/1 lc:ft tmtreated for u1eotl!a 7 days. Animnls iu sroups I. 2 wu! J were sacrificed on day 15. Group 4 (20 mice} received a single dose-of 5-FU (160 mg!kg) by ;,ztraperiloneal route in t!le stft day, Group 5 (20 mict:) reccil'ctl GS/1 i11 dnily doses jrJr the first 7 doy.v followed by n .ingle dose of 5-FU in the 8 111 dny, Graul' 6 (20 mict:) received G-CSF i11 daily doses fortlte first 7 days followed by o single dose of 5-FU in the 8'11 dny and group 7 o{animnls (20 mice) rei:eit>ed da ily doses of botft GSH t1nd G-CSF for tl1e first 7 days follo wed by a single Hose of 5-FU in the 8tll dny. Animals in groups 4, 5. 6 and 7 were di1•icled into 2 .wbgroups; subgroup a: 10 m ice were sacrificed 011 day 9 i. e. I clay after 5-FU adminislrutiou nnd subgroup b: 10 mice were sacrificed 0 11 day 15 i.e. !week after 5-FU administratio11. Mice were sacrificed by Clll throat all({ blood sainples were obtni11ed for determination of haemoto!ogical values; lwemoglvbilt (Hb). luwmatocrite value (liCT). mean corpuscular haemoglobin concentration (MCHC). mean corpit.~culur l'olume (MCV), 'mean corpuscularlwemoglobin (MCH), as well as total (TLC) and tlif fen:ntinl (DLC) leucocyte cowtt. Theu dissection of mice was done •where the right femurs were used for bon<' '"''rmll' cytology, w(,ile left femurs were used for bone marrow histopathology. In groups 5o given GSII pretreutmellt aud 6a gi ven G •CSF pretreatme11t (where mice killed I day after 5-FU dose) prote<:tion WIIS demoustrated regarding nertlropenia, bon~ marrow cytology and histopathology. lncompletC' protectiolt was revealed in mice recei1 1 ed GSH prefreatment or G-CSF prelreatment and killed I week after 5-FU dose (groups 5b and 6b respecti!Jely), while grm~ps la oud 7b give11 combiued GSH aud G-CSF pretreatment revealed uo protection .