Anti‐Clastogenic Effect of Berberine against DMBA‐Induced Clastogenesis

Abstract

Our aim was to evaluate the protective effect of berberine on 7,12-dimethylbenz [a]anthracene (DMBA)-induced chromosomal aberrations and micro-nucleated polychromatic erythrocytes (MnPCEs) frequency in bone marrow cells of golden Syrian hamsters. The anti-clastogenic effect of berberine (50 mg ⁄ kg b.w. p.o.) was also assessed by measuring the status of phase II detoxification enzymes and oxidative stress, as biochemical endpoints, during DMBA (30 mg ⁄ kg b.w. i.p.) induced clastogenesis. Marked chromosomal aberrations, increased MnPCEs frequency and enhanced status of lipid peroxidation, antioxidants and phase I and II detoxification enzymes were noticed in hamsters treated with DMBA alone. Oral pretreatment with berberine for 5 days to DMBA-treated hamsters significantly reduced the frequency of MnPCEs and chromosomal abnormalities as well as reversed the status of lipid peroxidation, antioxidants and phase I and II detoxification enzymes. The present study thus suggests that berberine has potent anti-clastogenic potential against DMBA-induced clastogenesis, which is probably due to its anti-lipid peroxidative potential and effect on modulation of phase I and II detoxification cascade.Somatic cell mutation plays a crucial role in the initiation and promotion of carcinogenesis. Polycyclic aromatic hydrocarbons exert mutagenic and carcinogenic effects in biological systems if they are metabolically activated to more reactive forms [1]. 7,12-Dimethylbenz[a]anthracene (DMBA), a potent and best characterised organ-specific carcinogen, attacks DNA through its active metabolite 4-dihydrodiol-1,2-epoxide. DMBA firmly binds to epidermal DNA and generates a complex DNA adduct profile [2]. DMBA is therefore widely used to induce clastogenesis in experimental animals.The investigation of new anti-clastogenic and anti-carcinogenic compounds is essential in the modern human civilization due to rise in undesirable genetic mutations and increase in cancer risk [3]. In vivo models with laboratory animals are the reliable approaches to predict the clastogenic or anti-clastogenic potential of natural or synthetic agents [4]. Bone marrow cells were commonly employed as a tool for the evaluation of clastogenic and anti-clastogenic efficacy of carcinogens and anti-cancer compounds, respectively. An abnormality in chromosomal structure (translocation, deletion, duplication) and chromosomal number due to exposure to chemical carcinogen and ⁄ or mutagen is associated with increased risk of cancer and in the progression of neoplastic transformation [5]. Gaizev et al. and Hayashi et al. reported that measurement of micronuclei in polychromatic erythrocytes is suitable to identify a mutagenic substance due to the reason that their macronucleus is extruded in the processes of their formation from erythroblasts [6,7]. Also, it is easy to examine chromosomal aberrations in the metaphase stage due to its compact arrangement [8].Though a battery of genotoxicity tests is used to evaluate the anti-clastogenic effect of medicinal plant...

Anticarcinogenic effect of alpha-lipoic acid and <i>Jatropha gossypifolia</i> leaves against cypermethrin-induced genotoxicity in rats

“…The result shown in Figure 1 above is in agreement with the findings of Ganapathy and Shanmugam (2010) in which the administration of 7,12-dimethylbenz[a]anthracene (DMBA) significantly increased the frequency of mPCEs in the bone marrow and consequent oral supplementation with berberine markedly reduced the frequency of mPCEs. Hammam and El-Khatib (2004) also studied the genotoxic effect of diazinon on male rats using dipping and spraying method.…”

Lycopene: Multitargeted Applications in Cancer Therapy

“…Combretastatin A4 phosphate is a VAD isolated from Combretum caffrum and has been reported to be antimitotic and antiangiogenic, along with the microtubule-depolymerizing property [40]. Substances like berberine, a protoberberine alkaloid found in the roots, rhizomes, stems and bark of berberis, goldenseal (Hydrastis canadensis) and Coptis chinensis, have also been reported to inhibit different types of cancer [41][42][43][44][45][46][47][48][49]. They act by inhibiting angiogenesis and by other mechanisms in different cancer models.…”

Cytotoxic Effect ofCoscinium fenestratumon Human Head and Neck Cancer Cell Line (HN31)

“…Berberine has been shown to inhibit the growth of tumor cell lines including cell lines of breast cancer [ 21 ], melanoma [ 22 ], liver cancer, and pancreatic cancer [ 23 ]. Moreover, berberine has been shown to have an antimutagenic effect on animal models [ 24 ] and to decrease the invasive properties of various tumors [ 25 – 35 ]. Other studies have demonstrated that berberine obtained from C. fenestratum has an antiproliferative effect on human nonsmall cell lung adenocarcinoma (NCI-H838 cell line) [ 36 ], colorectal cancer cells [ 37 ], and acute myeloid leukemia (HL-60 cell line) [ 38 ].…”