Elecampane rhizome extract alleviates methotrexate-induced hepatotoxicity and nephrotoxicity in male rats

Fatemeh Sharifi,Vahid Jazi,Elham Assadi Soumeh 경희대학교 융합한의과학연구소 2023 Oriental Pharmacy and Experimental Medicine Vol.23 No.4

Methotrexate (MTX) is a chemotherapy drug used to treat cancer and inflammatory diseases; however, its clinical applicability is limited due to its cytotoxic nature. The present study tested elecampane (Inula helenium L.) rhizome extract (ERE) for its protective effects against MTX-induced hepatotoxicity and nephrotoxicity in male rats. The rats were divided into five experimental groups (n = 10): control (physiological saline); MTX, physiological saline, and MTX [40 mg/kg intraperitoneal (i.p.)] on the fourth day; and three groups in which rats concurrently received MTX plus three doses of ERE (100, 200, 400 mg/kg) orally for 10 consecutive days. The findings revealed that MTX administration substantially elevated serum concentrations of total cholesterol (TC), low-density lipoproteins cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen, and creatinine. Additionally, it increased malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrotic factor-α (TNFα) levels in the liver and renal tissues while decreasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. However, treatment with ERE at a dosage of 400 mg/kg reversed the adverse effects of MTX toxicity by decreasing the levels of TC, LDL-C, MDA, AST, ALT, ALP, IL-1β, TNFα and increasing the activities of GPx, CAT, and SOD in the tissues mentioned above. A histological examination of the liver and renal tissues also confirmed the ameliorating effects of ERE. The present study indicated that EER could inhibit MTX-induced hepatotoxicity and nephrotoxicity by improving antioxidant defense and decreasing oxidative stress and inflammation.

Hormone Receptor Expression and Clinicopathologic Features in Male and Female Breast Cancer

Shandiz, Fatemeh Homaei,Tavassoli, Aliraz,Sharifi, Nourieh,Khales, Sima Ardalan,Kadkhodayan, Sima,Khales, Sahar Ardalan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Male and female breast cancers were investigated for variation in the clinicopathologic characteristics and expression of steroid hormone receptors in the northeast of Iran. Materials and Methods: Tumor specimens of 17 males and 338 females with breast cancer were collected at the hospitals of Mashhad University of Medical Sciences. Immunohistochemical expression of hormone receptors and clinicopathologic features of breast cancer were compared between two groups. Results: The mean age in men was 15 years higher than women (p=0.000). Males and females were mainly in stage II and III respectively (p=0.007). Although more than 60% of male and female patients were grade II, the respective figures for grade I and III were 25% and 12.5% in men but 7.1% and 27.2% in women respectively (p=0.025). ER was significantly more positive in men against women; 82.3% versus 53.4% (p=0.016). The related measures for PR was 58.8% and 50.3%, respectively (p=0.424). Males also showed significantly more ER expression than postmenopausal females; 82.3% versus 48.9% (p=0.010). Conclusions: Breast cancer in males and females contrasted in age at diagnosis, histological type, stage, grade and ER expression which emphasize they are separate diseases with different behaviors.

Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its Relation with Disease-free Survival

Shandiz, Fatemeh Homaei,Shabahang, Hossein,Afzaljavan, Fahimeh,Sharifi, Nourieh,Tavasoli, Alireza,Afzalaghaee, Monavar,Roshanzamir, Emane,Pasdar, Alireza Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. Materials and Methods: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. Results: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. Conclusions: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.

Antileishmanial and Cytotoxic Effects of Essential Oil and Methanolic Extract of Myrtus communis L.

Hossein Mahmoudvand,Fatemeh Ezzatkhah,Fariba Sharififar,Iraj Sharifi,Ebrahim Saedi Dezaki 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.1

Rhoptry antigens as Toxoplasma gondii vaccine target

Masoud Foroutan,Fatemeh Ghaffarifar,Zohreh Sharifi,Abdolhosein Dalimi,Ogholniaz Jorjani 대한백신학회 2019 Clinical and Experimental Vaccine Research Vol.8 No.1

Toxoplasmosis is a cosmopolitan zoonotic infection, caused by a unicellular protozoan parasite known as Toxoplasma gondii that belongs to the phylum Apicomplexa. It is estimated that over one-third of the world’s population has been exposed and are latently infected with the parasite. In humans, toxoplasmosis is predominantly asymptomatic in immunocompetent persons, while among immunocompromised individuals may be cause severe and progressive complications with poor prognosis. Moreover, seronegative pregnant mothers are other risk groups for acquiring the infection. The life cycle of T. gondii is very complex, indicating the presence of a plurality of antigenic epitopes. Despite of great advances, recognize and construct novel vaccines for prevent and control of toxoplasmosis in both humans and animals is still remains a great challenge for researchers to select potential protein sequences as the ideal antigens. Notably, in several past years, constant efforts of researchers have made considerable advances to elucidate the different aspects of the cell and molecular biology of T. gondii mainly on microneme antigens, dense granule antigens, surface antigens, and rhoptry proteins (ROP). These attempts thereby provided great impetus to the present focus on vaccine development, according to the defined subcellular components of the parasite. Although, currently there is no commercial vaccine for use in humans. Among the main identified T. gondii antigens, ROPs appear as a putative vaccine candidate that are vital for invasion procedure as well as survival within host cells. Overall, it is estimated that they occupy about 1%-30% of the total parasite cell volume. In this review, we have summarized the recent progress of ROPbased vaccine development through various strategies from DNA vaccines, epitope or multi epitope-based vaccines, recombinant protein vaccines to vaccines based on live-attenuated vectors and prime-boost strategies in different mouse models.

Antiproliferative Activity of Marrubium persicum Extract in the MCF-7 Human Breast Cancer Cell Line

Hamedeyazdan, Sanaz,Fathiazad, Fatemeh,Sharifi, Simin,Nazemiyeh, Hossein Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Aim: Developing antitumor drugs from natural products is receiving increasing interest worldwide due to limitations and side effects of therapy strategies for the second leading cause of disease related mortality, cancer. Methods: The antiproliferative activity of a methanolic extract from the aerial parts of Marrubium persicum extract was assessed with the MCF-7 breast cancer cell line using the MTT test for cell viability and cytotoxicity indices. In addition, antioxidant properties of the extract were evaluated by measuring its ability to scavenge free DPPH radicals. Moreover, the total phenolic and flavonoid content of the extract was determined based on Folin-Ciocalteu and colorimetric aluminum chloride methods. Results: The findings of the study for the antiproliferative activity of the methanolic extract of M. persicum showed that growth of MCF-7 cells was inhibited by the extract in a dose and time dependent manner, where a gradual increase of cytotoxicity effect has been achieved setting out on 200 ${\mu}g/mL$ concentration of the plant extract. The antioxidant assay revealed that the extract was a strong scavenger of DPPH radicals with an $RC_{50}$ value of 52 ${\mu}g/mL$. The total phenolic and flavonoids content of the plant extract was 409.3 mg gallic acid equivalent and 168.9 mg quercetin equivalent per 100g of dry plant material. Conclusion: Overall, M. persicum possesses potential antiproliferative and antioxidant activities on the malignant MCF-7 cell line that could be attributed to the high content of phenolics and flavonoids, and therefore warrants further exploration.

Luteolin-loaded Phytosomes Sensitize Human Breast Carcinoma MDA-MB 231 Cells to Doxorubicin by Suppressing Nrf2 Mediated Signalling

Sabzichi, Mehdi,Hamishehkar, Hamed,Ramezani, Fatemeh,Sharifi, Simin,Tabasinezhad, Maryam,Pirouzpanah, Mohammadbagher,Ghanbari, Parisa,Samadi, Nasser Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.