Showing papers on "7,12-Dimethylbenz[a]anthracene published in 2021"

Anticancer activity of Vicenin-2 against 7,12 dimethylbenz[a]anthracene-induced buccal pouch carcinoma in hamsters.

Abstract: Buccal mucosa carcinoma is a significant cause of death in developing nations. Vicenin-2 is a significant bioactive compound found in Ocimum sanctum Linn or Tulsi that possesses several pharmacologic properties. Our focus is to understand the possible impact of Vicenin-2 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters. Buccal carcinoma was induced by treatment with carcinogenic DMBA, three times a week for 14 weeks. We determined 100% tumor incidence, abnormal tumor volume, inclined tumor burden, and deduced body weight in DMBA-induced oral squamous cell carcinoma (OSCC) hamsters. The upregulation of cytokine levels (interleukin [IL]-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) was observed in DMBA-induced OSCC hamsters. Moreover, dysplastic, hyperplastic, and squamous cell carcinoma was identified in the DMBA-induced OSCC hamsters. The diminished activities of lipid peroxidation and enzymatic/nonenzymatic antioxidants were observed in DMBA-induced hamsters. Furthermore, the high expression of proliferating cell nuclear antigen (PCNA), Cyclin-D1, and Bcl-2, and attenuated Bax expression were observed in DMBA-induced hamsters. Our study results explored that Vicenin-2 (30 mg/kg) treated with DMBA-brushed hamsters averted tumor incidence, improved the antioxidant status, and inhibited lipid peroxidation. Moreover, Vicenin-2 inhibited the immunohistochemical expression of PCNA, Cyclin-D1, and Bcl-2, and significantly restored apoptotic Bax levels. The Vicenin-2 treatment prevents the lesion formation in the oral epithelium of the DMBA-induced hamsters. The Vicenin-2 treatment potentially halts the proinflammatory cytokines (IL-6, IL-1β, and TNF-α) production in OSCC hamsters. Thus, we proved that Vicenin-2 prevents DMBA-induced buccal carcinogenesis in hamsters via improving antioxidants by modulating apoptotic and cytokines signaling pathways.

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12-dimethylbenz[a]anthracene-induced hamster oral cancer via the down-regulation of PI3K/AKT/mTOR signaling pathways.

Abstract: Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

Kirenol regulates the cell proliferative and inflammatory markers in DMBA-induced oral squamous cell carcinogenesis in hamster.

Abstract: This present findings hypothesized the modulatory effects of kirenol on expression pattern of cell proliferative and inflammatory markers during DMBA induced HBP carcinogenesis. The machinery pathways for chemomodulatory effect of kirenol was investigated by analyzing the levels of antioxidants histological changes, lipid peroxidation and molecular expression pathway of PCNA, NF-κB in the DMBA only painted HBPC. Oral cancer was developed in the HBP model by DMBA (0.5%) three times a week for 14th weeks. We analyzed body weight with deregulated molecular expressions pattern of PCNA and NF-κB was noticed in the DMBA induced hamsters compared to control hamsters. Oral administration of kirenol 30 mg/kg bw, to DMBA induced hamster models reverted the activity of the biochemical markers in Group 4. Besides, tumor tissues of hamsters receive antioxidant capability from kirenol exclaimed significant modifications in DMBA induced causes: inhibits cell proliferation (inhibits PCNA expression) and suppresses inflammation (decreased NF-κB expression) of markers. Taken together, the protective effect of that kirenol an augmenting inflammation of the started cells and exhibited antiproliferative, anti-inflammatory, antilipid peroxidative and restores the xenobiotic enzymes levels (phase I and II) system and enhances antioxidant properties in oral carcinoma hamsters, in which turn, is reflected diminished tumor burden, volume, and multiplicity.

[6]‐Gingerol impedes 7,12‐dimethylbenz(a)anthracene‐induced inflammation and cell proliferation‐associated hamster buccal pouch carcinogenesis through modulating Nrf2 signaling events

Abstract: The present study examines the chemopreventive role of [6]-gingerol, an active component of ginger, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis models. The HBP has been developed with an addition of 0.5% of DMBA to the HBP area three times per week, up to the end of the 16th experimental week. At the end of the experiment, we noticed 100% tumor incidence and precancerous lesions, such as dysplasia, hyperplasia, keratosis, and well-differentiated squamous cell carcinoma, in DMBA-induced HBP. Furthermore, we observed that [6]-gingerol inhibited the increased thiobarbituric acid-reactive substances and decreased antioxidant levels in DMBA-induced hamsters. Moreover, [6]-gingerol inhibits DMBA-exposed over expression of inflammatory markers (inducible nitric oxide synthase, interleukin [IL]-1β, IL-6, cyclooxygenase-2, and tumor necrosis factor-α) and cell proliferation markers (cyclin D1, proliferating cell nuclear antigen); induces proapoptotic markers in HBP. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a major antioxidant transcription factor, which regulates the antioxidant gene-dependent scavenge of tumor proliferation and apoptosis. Overexpression of Nrf2 signaling plays a pivotal role and can be a novel target in preventing carcinogenesis. In this study, [6]-gingerol restores the DMBA-induced depletion of Nrf2 signaling and thereby prevents buccal pouch carcinogenesis in hamsters. These results point out that [6]-gingerol impedes the responses of inflammatory and cell proliferation-associated progression of cancer through the action of Nrf2 signaling.

Vitamin K protects against 7,12-dimethylbenz(A)anthracene induced hepatotoxicity in Wistar rats

Abstract: Humans are daily exposed to 7,12-dimethylbenz(a)anthracene (DMBA), a well known polycyclic aromatic hydrocarbons (PAH). This study investigated the role of dietary intake of Vitamin K (VK), a polyphenolic compound, with potential antioxidative properties, against DMBA-induced hepatotoxicity. Sixty experimental animals (120-150 g) were divided into six groups (A-F): Control, DMBA (80 mg/kg bw) only, VK (0.00 g/10 kg) diet only, VK (7.5 g/10 kg) diet only, DMBA + VK (0.0 g/10 kg) diet and DMBA + VK (7.5 g/10 kg) diet. Single oral administration of DMBA (80 mg/kg body weight) to Wistar rats resulted in hepatic damage after 16 weeks. DMBA significantly (P <.05) decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx). Levels of reduced glutathione (GSH) and Vitamin C were significantly decreased with increase in malondialdehyde (MDA) and nitric oxide (NO) levels in serum and liver. Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), I³-glutamyltransferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were significantly (P <.05) elevated in the serum but reduced in the liver of DMBA-administered group. Ingestion of 7.5 g/10 kg VK diet prevented the up regulations in inflammatory biomarkers (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 17A (IL-17A)) which elicited liver damaged in the DMBA-treated group. DMBA induced hepatic alterations in DMBA-treated group but was restored to near normal in VK (7.5 g/10 kg) diet group. These findings suggest the protective potential of increased dietary intake of vitamin K against DMBA-induced hepatic dysfunction. © 2020 Wiley Periodicals LLC.

Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer.

Abstract: Breast cancer is the most common estrogen-dependent cancer in the world. Hormone therapy for this cancer can be neoadjuvant and/or adjuvant. Herbal remedies with antiproliferative properties are believed to be potential anticancer agents. The aqueous extract of Dacryodes edulis (Burseraceae) leaves (AE), a medicinal plant used against cancer in Cameroon, was found to display antiproliferative effects in ovariectomized rats. Compounds isolated from this plant exhibited anticancer activity in vitro. To determine whether AE has an anticancer potential, its effects were investigated in rats with already developed breast cancer. Mammary tumors were induced by a single subcutaneous administration (under the mammary gland) of 7,12-dimethylbenz[a]anthracene (DMBA; 50 mg/kgBW) to immature female rats. After 22–26 weeks of observation, animals with palpable tumors were treated with tamoxifen (3.3 mg/kgBW) and AE at doses of 25 and 100 mg/kgBW. The negative control received distilled water. Treatments were given orally for 21 consecutive days. The volume of mammary tumors was evaluated weekly using a caliper. On day 22, animals were sacrificed. Cholesterol and estradiol levels were assessed in serum, breast tumors, mammary glands, and ovaries. Oxidative status of tumors was evaluated. The histological analysis of mammary glands and breast tumors was performed. Results showed that AE reduced tumor volume and weight ( ). This effect was associated with reduced cholesterol ( ) and estradiol ( ) levels in breast tumors, serum, ovaries, and mammary glands. AE also increased tumors levels of malondialdehyde ( ) and antioxidant enzymes ( ). These effects contributed to the decrease in the size of breast alveoli ( ), the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the aqueous extract of D. edulis leaves, thanks to its ability to inhibit tumor growth, could be considered as a potential alternative for the neoadjuvant treatment of estrogen-dependent breast cancer.

Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c Trp53 knockout mice.

Abstract: Chemical carcinogens, such as 7,12-dimethylbenz[a]anthracene (DMBA) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), are known to induce mammary carcinomas in mice and rats. In the present study, the phenotypic and genotypic characteristics of carcinogen-induced mammary carcinogenesis in heterozygous BALB/c tumor protein p53 (Trp53) knockout mice were examined with reference to published data surrounding human breast cancer. A significantly accelerated induction of mammary carcinomas was observed following a single dose of DMBA (50 mg/kg of body weight at 7 weeks of age), and a modest acceleration was induced by PhIP (50 mg/kg of body weight) administered by gavage 6 times/2 weeks from 7 weeks of age. DMBA-induced mammary carcinomas were histopathologically characterized by distinct biphasic structures with luminal and myoepithelial cells, as well as a frequent estrogen receptor expression, and PhIP-induced carcinomas with solid/microacinar structures consisted of pleomorphic cells. Of note, DMBA-induced mammary carcinomas were characterized by a HRas proto-oncogene (Hras) mutation at codon 61, and gene/protein expression indicating MAPK stimulation. PhIP-induced lesions were suspected to be caused by different molecular mechanisms, including Wnt/β-catenin signaling and/or gene mutation-independent PI3K/AKT signaling activation. In conclusion, the present mouse mammary carcinogenesis models, induced by a combination of genetic and exogenous factors, may be utilized (such as the DMBA-induced model with Trp53 gene function deficiency as a model of adenomyoepithelioma, characterized by distinct biphasic cell constituents and Hras mutations), but PhIP-induced models are required to further analyze the genetic/epigenetic mechanisms promoting mammary carcinomas.

Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.

Abstract: The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.

Chemopreventive effect of dieckol against 7,12-dimethylbenz(a)anthracene induced skin carcinogenesis model by modulatory influence on biochemical and antioxidant biomarkers.

Abstract: Skin cancer is the commonly found type, which contributes to 40% of whole cancer incidences worldwide. Dieckol is an active compound occurs in the marine algae with many biological benefits. In this exploration, we intended to investigate the therapeutic potency of dieckol against the 7,12-dimethylbenz(a)anthracene (DMBA)-triggered skin carcinogenesis in mice. The skin cancer was stimulated to the animals via injecting the 25 μg of DMBA in 100 μL of acetone in shaved dorsal portion along with the 30 mg/kg of dieckol supplementation for 25 week. The antioxidant enzymes and phase-I and -II detoxifying enzymes in the test animals were inspected via standard protocols. Pro-inflammatory markers (IL-6, IL-1β, and TNF-α) level was examined via ELISA kits and the expression of inflammatory molecular markers like p-NF-ƙB, IƙBα and p-IƙBα were studied through western blotting. The expression status of pro- and anti-apoptotic proteins (p53, Bax, Bcl-2, caspase-3, caspase-9, COX-2, TGF-β1) was investigated via real-time polymerase chain reaction (RT-PCR). Our results revealed that the 30 mg/kg of dieckol supplementation noticeably regained the body and liver weight and also diminished the tumor incidence in the DMBA-incited animals. Dieckol treatment exhibited an enhanced antioxidants (SOD, CAT, GPx, and GSH) and reduced phase-I enzymes Cyt-p450 and Cyt-b5 in the DMBA-induced animals. Dieckol also diminished the pro-inflammatory modulators like IL-6, IL-1β and TNF-α. Western blotting result evidenced that the dieckol was inhibited the IƙB/NF-ƙB signaling pathway. RT-PCR study proved the enhanced expression of pro-apoptotic protein (p53, Bax, caspase-3 and -9) in the dieckol treated animals. Histological study also confirmed the therapeutic benefits of Dieckol. Altogether with these findings, it was clear that the dieckol has appreciably allayed the DMBA activated skin tumorigenesis in the mice and it could be a promising agent to treat the human skin cancer in future.

Optimization of 7,12‑dimethylbenz(a)anthracene‑induced rat epithelial ovarian tumors

Abstract: Ovarian carcinoma is the second most common malignant tumor of the female reproductive system and an notable cause of cancer death. The detection and diagnosis of early ovarian carcinomas are still clinical challenges, which calls for imaging studies using early ovarian carcinoma animal models. The present study aimed to optimize the 7,12-dimethylbenz(a)anthracene (DMBA)-induced model of rat ovarian tumors by investigating the delivery methods, induction dose and time of DMBA exposure, and explored the morphological features of tumors using MRI. Three schemes were performed. In scheme one the ovary was covered with absorbable hemostatic gauze loaded with a high concentration of liquid DMBA. For this scheme, 150 Sprague-Dawley rats were divided into three groups depending on the DMBA dose (1.0, 2.0 and 3.0 mg). In scheme two DMBA solution was injected under the ovarian capsule. For this scheme, 159 rats were divided into 0.5, 1.0 and 1.5 mg DMBA groups. In scheme three the ovary was covered with absorbable gauze loaded with a high concentration of solid DMBA. For this scheme 161 rats were divided into 1.0, 2.0 and 3.0 mg DMBA groups. Each group of the three schemes was further subdivided into 60-, 90-, 120-, 150- and 180-day groups. In scheme two, the tumor formation rate was 75.6% (99/131), which was the highest in the 1.5 mg group (86.4%, 38/44) and reached 100% (10/10) on day 120. The induced tumors were serous in 93.9% (93/99) of tumors. Borderline ovarian tumors accounted for 19.2% (19/99) of all tumors, and ovarian cancer accounted for 46.5% (46/99). The mean maximum diameter (MMD) of borderline ovarian tumors was 10.29±3.41 mm, and that of ovarian cancer was 15.19±7.10 mm. MMD of the solid components increased with increasing malignancy. Cystic, cystic-solid and solid tumors were observed. The ovarian subcapsular injection of 1.5 mg DMBA was the best scheme for the rat ovarian tumor model. The present model is ideal for investigating the occurrence, development and imaging of ovarian tumors.

Cytotoxic and cancer chemopreventive potentials of the Anthonotha macrophylla P. Beauv aqueous extract on 7,12-dimethylbenz[a]anthracene-induced breast cancer in rats

Abstract: Breast cancer is one of the leading causes of cancer deaths in women worldwide. Many women rely on plants as alternatives to prevent/treat cancer. Anthonotha macrophylla (Ceasalpiniaceae) is one of this ethnomedicinal plant used to cure cancer in Cameroon. This study was therefore undertaken to bring scientific evidence to this claim. The in vitro cytotoxicity of A. macrophylla aqueous extract was evaluated using resazurin reduction assay in five tumors and two non-tumor cell lines. Moreover, the chemopreventive potential of A. macrophylla aqueous extract was evaluated on 7,12 dimethylbenz[a]anthracene (DMBA) induced breast cancer in rats. The research focused on the incidence, burden, volume and histological analysis of breast tumors. In vitro, A. macrophylla extract exhibited cytotoxic effect in all tested cell lines with a CC50 ~ 279 and 132 μg/mL in human (MCF-7 and MDA-MB-231) and rodent breast cancer cells, respectively after 24 h. In vivo, the untreated DMBA-rats presented 100% of tumor incidence, while no tumor was detected in normal rats. Interestingly, a seven-month oral administration of A. macrophylla extract at the doses of 75 and 150 mg/kg BW resulted in a significant decrease of tumor incidence (p < 0.01 and p < 0.05), burden (70.01% and 53.28%) and volume (p < 0.001 and p < 0.01) compared to DMBA rats. The presence of polyphenols in the aqueous extract of Anthonotha macrophylla, as well as its antiradical properties, may account for its antitumor effects. These results therefore support the traditional use of Anthonotha macrophylla against breast cancer.

Modulatory Effect of 4-(methylthio)butyl Isothiocyanate Isolated From Eruca Sativa Thell. on DMBA Induced Overexpression of Hypoxia and Glycolytic Pathway in Sprague-Dawley Female Rats.

Abstract: 4-(methylthio)butyl isothiocyanate (4-MTBITC) is a hydrolytic product from the plant Eruca sativa Thell. In the present study, we explored the anti-cancer effect of 4-MTBITC against 7,12-dimethylbenz [a] anthracene (DMBA) induced breast cancer. Hypoxic conditions were developed using a single dose of 60 mg/kg DMBA. Hepatic and renal parameters were increased along with antioxidants in cancer-bearing rats which were lowered with the treatment of 4-MTBITC. Further, it inhibited the up-regulation of glycolytic enzymes caused by DMBA. The hypoxia pathway was evaluated using RT-PCR and it was found that the 40 mg/kg doses of 4-MTBITC statistically lowered the expression of HIF-1α. Akt/mTOR signaling pathway was one of the major pathways involved in 4-MTBITC-induced cell growth arrest by western blotting. Amino acid profiling serum-free plasma revealed the downregulation of specific amino acids required for vital components of fast-growing cancer cells. 4-MTBITC reduced the levels of serine, arginine, alanine, asparagines, and glutamic acid. Histological examination also showed neoplastic growth following DMBA doses. 4-MTBITC treated rats showed less infiltration and normal physiology. Our findings for the first time demonstrated the potential therapeutic significance of 4-MTBITC on modulation of glycolytic enzymes and hypoxia pathway in female rats.

Effects of ethanol extract of curry leaves (Murraya koenigii) on HER2 and caspase-3 expression in rat model mammary carcinoma.

Abstract: Background and Aim Human epidermal growth factor receptor 2 (HER2/erbB2/neu) is a prognostic factor and biomarker for detecting mammary tumor malignancy. Leaves of curry (Murraya koenigii) contain alkaloid, flavonoid, and phenolic compounds that can be cytotoxic to tumor cells. Caspase-3 is an indicator of apoptosis in tumor cells. This study aimed to evaluate the effect of curry leaf extract on the expression of HER2 and caspase-3 in mammary tumor through immunohistochemical analyses. Materials and Methods Thirty five Sprague-Dawley rats were divided into seven groups: negative control of tumor (P1), positive control of tumor (P2), tumor therapy with methotrexate (P3), and curry leaf extract doses of 300 and 400 mg/kg body weight/BW after tumor formation (P4, P5), and before tumor formation (P6, P7). Thirty rats of six groups were injected subcutaneously into the mammary glands with 7,12-dimethylbenz(α)-anthracene DMBA) twice within 2 weeks for mammary tumor formation. At the end of the treatments, the rats were euthanized, and their mammary glands were analyzed histopathologically and immunohistochemically using HER2 and caspase-3 antibodies. Results Regarding the expression of HER2 detected in the epithelial cell membrane of the mammary gland, P2, P3, P4, and P5 revealed positive expression, P6 and P7 showed equivocal expression, while P1 showed negative expression. Regarding caspase-3 expression in the cytoplasm of epithelial cells, it was low in P1, moderate in P2, P5, P6, and P7, and high in P3 and P4. These findings suggest that DMBA injection produced mammary tumors with HER2 as a biomarker of mammary tumor, and high caspase-3 expression in P4 was the effect of curry leaves extract. Conclusion The extract of curry leaves at a dose of 300 mg/kg BW with preventive and curative effects can potentially be used as an anti-tumor agent, which effectively induces the apoptosis of tumor cells.

Protective and curative mechanisms of echinochrome against 7, 12-Dimethylbenz[a]anthracene -induced renal toxicity in rats

Abstract: Echinochrome (Ech) is one of the most important bioactive substance which is found in shells, spines, and eggs of the sea urchins. Aim: the present study was carried out to evaluate the curative and protective effects of Ech pigment against DMBA -induced renal toxicity in rats. Methods: Experimental rats were assigned into two main groups; protective group (treated with Ech for 14 days then administrated DMBA) and curative group (administrated DMBA then treated with Ech for 14 days). Each group is divided into 3 sub-groups; control, DMBA (15 mg/ kg body, weight orally), and Ech (1 mg/ kg body, weight orally). Results: The oral administration of Ech decreased the concentrations of urea, creatinine, uric acid, and MDA and increased GSH and CAT levels in both protective and curative groups. Moreover, histology of kidney tissue improved after the treatment with Ech. Conclusions: The results of the present study demonstrated the potential protective and curative activities of Ech against renal toxicity induced by DMBA through inhibiting the metabolism of DMBA and restoring the balance between ROS formation and internal antioxidant enzymes by its powerful antioxidant activity.

Moringa oleifera and Musa sapientum ameliorated 7,12-Dimethylbenz[a]anthracene-induced upregulations of Ki67 and multidrug resistance 1 genes in rats.

Abstract: Objectives Moringa oleifera (MO) and Musa sapientum (MS) are plants of ethnomedicinal importance. We evaluated the effects of MOF6 (extracted from MO leaves) and MSF1 (extracted from MS suckers) on immunomodulations of Ki67 (proliferation biomarker) and multidrug resistance 1 (MDR1) genes in the liver of rats in 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hepatotoxicity and mutagenesis to determine their antiproliferation, anti-drug resistance, and anticancer potentials. Methods Forty-five adult male rats were randomly divided into nine groups (n = 5). Groups 1 and 2 received physiological saline and 15 mg/kg bodyweight of DMBA, respectively. Groups 3 and 4 received 15 mg/kg bodyweight DMBA and were treated with 15 and 30 mg/kg bodyweight of MOF6, respectively. Group 5 received 15 mg/kg bodyweight DMBA and was treated with 10 mg/kg bodyweight of MSF1. Group 6 received 15 mg/kg bodyweight DMBA and was treated with 3.35 mg/kg bodyweight of doxorubicin and intravenous injection of 0.5 ml/200 g of cisplatin. Groups 7-9 received only 15 and 30 mg/kg bodyweight of MOF6 and 10 mg/kg bodyweight of MSF1, respectively. DMBA, doxorubicin, and extracts doses were administered orally. The duration of our experimental procedure was 8 weeks. Consequently, liver histopathology (hematoxylin and eosin technique) and enzyme-linked immunosorbent assay homogenates' concentrations of Ki67 and MDR1 were evaluated. Computed data were statistically analyzed (P ≤ 0.05). Results Results showed normal histoarchitectures of the liver in all groups. Statistical analyses showed significant (P ≤ 0.05) and non-significant decreased concentrations (P ≥ 0.05) of Ki67 and MDR1 in Groups 3-9 compared with Group 2. Therefore, MOF6 and MSF1 ameliorated DMBA-induced hepatotoxicity, abnormal proliferation, and drug resistance. Conclusion MOF6 and MSF1 possess antiproliferation, anti-drug resistance, and anticancer potentials.

Modulator effect of mangiferin on biochemical characterization in 7,12-dimethylbenz[a]anthracene induced oral cancer in experimental hamsters.

Abstract: Background Newly, chemo-preventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural based constituents. Malignancy urges to augment effectual chemo-preventive agents that are look forward to suppress the tumours which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related with the high prevalence of human oral cancer (OC) patients. Methods In the present research, we examined to assess antioxidants, lipid peroxidation (LPO) and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7.12-dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma (HCPC). OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks. Results 100% well defined OC establishment with body weight (bw), tumour burden (TB), antioxidant, LPO and liver marker enzymes and also histological changes were observed on DMBA-challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg bw, to DMBA painted hamsters were significantly averted the body weight, succession of tumour, the biochemical as well as histopathological changes. Conclusion Findings of this work clearly suggest that the anti-carcinoma effect of mangiferin possesses the modulator effects on potent antioxidant, anti-LPO and detoxification agents to expel the metabolites of malignant cells, on DMBA-provoked BPC in hamsters.

Nigella Sativa’s Protection Against 7,12 Dimethylbenz [A] Anthracene -Induced Colon Carcinogenesis in Rats

Abstract: Colon cancer is the third most common cause of death from cancer worldwide. Recently, natural products have been widely used as an alternative therapy for colon cancer. Previous studies have reported that Nigella sativa has chemopreventive activity in vitro and in vivo . This study aimed to evaluate the effect of Nigella sativa seed (NSS) on rat-colon cell after initiation of 7,12-dimethylbenz [ a ] anthracene . Rats were divided into five groups, 12 rats in each group: Group I was given 7,12dimetilbenz [ a ] anthracene (DMBA) orally 20 mg/kgBW twice a week for five weeks, group V is the solvent control group was given corn oil. The other three groups were given DMBA + NSS, at the dosage of 250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW. NSS extract was dissolved in corn oil and administered daily per oral during the next two weeks before and during the initiation of DMBA. After 16 weeks, all rats were sacrificed . H&E staining showed that necrosis activity was lower in treated groups compared to DMBA group. AgNOR staining show ed mAgNOR was significantly decrease following the increasing dose of NSS ( 250 mg/kgBW , 5 0 0 mg/kgBW and 7 50 mg/kgBW ) were subsequently 1 .62 ± 0 .086, 1 . 60 ± 0 .101 and 1 . 3 9 ± 0 .049 (p<0.05) . The results showed that NNS reduce the damage of colon cells and inhibit colon cell proliferation in DMBA induced rat s .