PURPOSE: Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against the human breast adenocarcinoma cell line (MCF-7) was investigated. METHODS: The cytotoxic effects of cytotoxin-II were determined by morphological analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mode and mechanism of cell death were investigated via acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis of cell death, detection of mitochondrial membrane potential, measurement of intracellular reactive oxygen species (ROS), annexin V/propidium iodide staining, and caspase-9 activity assays. RESULTS: The half maximal inhibitory concentration (IC50) of cytotoxin-II in MCF-7 cells was 4.18+/-1.23 microg/mL, while the value for cisplatin was approximately 28.02+/-1.87 microg/mL. Morphological analysis and AO/EtBr double staining showed typical manifestations of apoptotic cell death (in doses lower than 8 microg/mL). Dose- and time-dependent ROS generation, loss of mitochondrial membrane potential, caspase-9 activation, and cell cycle arrest were observed in their respective tests. CONCLUSION: In conclusion, cytotoxin-II has potent anticancer effects in the MCF-7 cell line, which are induced via the intrinsic pathways of apoptosis. Based on these findings, cytotoxin-II is a suitable choice for breast cancer treatment.
Adenocarcinoma* ; Antineoplastic Agents ; Apoptosis* ; Biological Products ; Breast Neoplasms ; Breast* ; Caspase 9 ; Cell Cycle Checkpoints ; Cell Death ; Cell Line* ; Cisplatin ; Cobra Venoms* ; Cytotoxins ; Diagnosis ; Elapidae ; Female ; Humans ; MCF-7 Cells ; Membrane Potential, Mitochondrial ; Peptides ; Reactive Oxygen Species ; Snakes ; Venoms

Objective: To detect the presence of specific CTX-M class of extended spectyum β-lactamases (ESBLs) in a collection of cephalosporin-resistant Enterobacteriaceae isolates from Bahrain. Methods: A subset of 80 cephalosporin-resistant Enterobacteriaceae collected from Salmaniya Medical Complex, Bahrain, were characterized further for the presence of specific genogroups of CTX-M β-lactamases by multiplex- and monoplex- PCRs. The primers used for the multiplex and monoplex PCRs were of genogroups- 1, 2, 8, 9 and 25. Sequencing of the representative isolates was performed to find the circulating CTX-M-types. Results: A total of 93.8% (75/80) isolates showed the amplicons corresponding to any of the genogroups (1, 2, 8, 9, 25) and the remaining 6.2% isolates turned out negative in multiplex PCR. Some of the isolates demonstrated multiple bands corresponding to the sizes of different genogroups. Further confirmation with respective monoplex PCR on these 75 isolates demonstrated that 93.3% (70/75) harbored CTX-M genogroup-1 and 6.7% (5/75) harbored genogroup-9. We did not find the presence of genogroups 2, 8, and 25 in these isolates by monoplex PCR. Sequencing results of genogroup-1 isolates demonstrated the presence of CTX-M-15-like ESBL, however, discrepant results were noticed in genogroup-9 isolates, sequencing showed them as CTX-M-55-like ESBL. Conclusions: This is the first report from Bahrain characterizing the CTX-M genogroups of ESBLs and reporting the emergence of bla

Objective: To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy. Methods: A single dose of streptozotocin (40 mg/kg) coupled with a fructose diet induced diabetes in Wistar rats. Agmatine (40 and 80 mg/kg) was administered to rats for 12 weeks. The body weight and fasting blood glucose were measured weekly. Insulin level, urine output, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C were also determined at the end of the experiment. Furthermore, superoxide dismutase, glutathione, interleukin-1β, interleukin-6, and tumor necrosis factor-alpha were evaluated in kidney tissue. Histopathological study was also performed using hematoxylin and eosin staining. Results: Agmatine at both doses significantly increased final body weight, and lowered fasting blood glucose, urine output, insulin, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C levels compared with the diabetic group (P < 0.05). Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats. Moreover, the histopathological changes in renal structure were ameliorated by agmatine treatment. Conclusions: Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress. The molecular mechanisms of its nephroprotective actions need to be investigated in future study.