TY - JOUR
T1 - Inhibition of precancerous lesions development in kidneys by chrysin via regulating hyperproliferation, inflammation and apoptosis at pre clinical stage
AU - Rashid, Summya
AU - Nafees, Sana
AU - Vafa, Abul
AU - Afzal, Shekh Muhammad
AU - Ali, Nemat
AU - Rehman, Muneeb U.
AU - Hasan, Syed Kazim
AU - Siddiqi, Aisha
AU - Barnwal, Preeti
AU - Majed, Ferial
AU - Sultana, Sarwat
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - Chrysin (CH) is natural, biologically active compound, belongs to flavoniod family and possesses diverse pharmacological activities as anti-inflammatory, anti-oxidant and anti-cancer. It is found in many plants, honey and propolis. In the present study, we investigated the chemopreventive efficacy of CH against N-nitrosodiethylamine (DEN) initiated and Fe-NTA induced precancerous lesions and its role in regulating oxidative injury, hyperproliferation, tumor incidences, histopathological alterations, inflammation, and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200 mg/kg bw) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated Fe-NTA enhanced renal lipid peroxidation, serum toxicity markers and restored renal anti oxidant armory significantly. CH supplementation suppressed the development of precancerous lesions via down regulation of cell proliferation marker like PCNA; inflammatory mediators like TNF-α, IL-6, NFkB, COX-2, iNOS; tumor incidences. CH up regulated intrinsic apoptotic pathway proteins like bax, caspase-9 and caspase-3 along with down regulation of Bcl-2 triggering apoptosis. Histopathological and ultra structural alterations further confirmed biochemical and immunohistochemical results. These results provide powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways.
AB - Chrysin (CH) is natural, biologically active compound, belongs to flavoniod family and possesses diverse pharmacological activities as anti-inflammatory, anti-oxidant and anti-cancer. It is found in many plants, honey and propolis. In the present study, we investigated the chemopreventive efficacy of CH against N-nitrosodiethylamine (DEN) initiated and Fe-NTA induced precancerous lesions and its role in regulating oxidative injury, hyperproliferation, tumor incidences, histopathological alterations, inflammation, and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200 mg/kg bw) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated Fe-NTA enhanced renal lipid peroxidation, serum toxicity markers and restored renal anti oxidant armory significantly. CH supplementation suppressed the development of precancerous lesions via down regulation of cell proliferation marker like PCNA; inflammatory mediators like TNF-α, IL-6, NFkB, COX-2, iNOS; tumor incidences. CH up regulated intrinsic apoptotic pathway proteins like bax, caspase-9 and caspase-3 along with down regulation of Bcl-2 triggering apoptosis. Histopathological and ultra structural alterations further confirmed biochemical and immunohistochemical results. These results provide powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways.
KW - Apoptosis
KW - Chrysin
KW - Hyper proliferation
KW - Inflammation
KW - Renal cell carcinoma
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=84978397833&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2016.07.004
DO - 10.1016/j.abb.2016.07.004
M3 - Article
C2 - 27403965
AN - SCOPUS:84978397833
SN - 0003-9861
VL - 606
SP - 1
EP - 9
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -
