Open Access Original Research Article

Effect of Cyclophosphamide and Its Combination with Metformin on the Survival Rate in Mice

Ahmad Alhowail, Sultan Sajid, Yasser Almogbel, S. I. Rabbani, Mansour Alsharidah

Journal of Pharmaceutical Research International, Page 1-6
DOI: 10.9734/jpri/2019/v30i230263

Background: Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, is widely used to treat several types of cancer. Its toxic effects are well-established and include hepatotoxicity, nephrotoxicity, and bone marrow suppression. Metformin (MET) is an anti-diabetic medication that is considered a first-line therapy for type 2 diabetes mellitus. In this study, we aimed to investigate the effect of co-administration of MET on CYP-induced toxicity by recording the survival rate in mice.

Methods: Fifty mice (body weight 30–35 gm) were divided into four groups as control and treatments and comprised of 12-13 animals of either sex. The animals in the control group received 4 doses of saline by injection. The animals in the CYP group received 4 doses of CYP (100 mg/kg) (intraperitoneal). The animals in the MET group received lower daily dose (30 mg/kg) in drinking water (3 mg/ml), starting 3 days prior to CYP injection and lasting until the final injection of CYP. The animals in the combination group (CYP and MET) received 4 doses of CYP (100 mg/kg) and a daily dose of MET in drinking water (3 mg/ml). The animals were observed daily to record the mortality and their body weights were recorded every alternate day. The data obtained from the study was statistically analyzed by one-way ANOVA, and p<0.05 was considered significant.

Results: The data obtained from the study indicated that CYP administration increased the rate of mortality significantly (p < 0.01) when compared to the control animals, while MET reduced the rate. When the combination of CYP and MET was tested, the mortality rate was found to be increased. Both CYP and MET significantly reduced the body weight compared to the control animals.

Conclusion: The results indicated that the combination of CYP and MET reduced the survival rate of animals, suggesting that although MET possesses anti-proliferative action, it has the potential to increase the toxic effects of CYP when combined with CYP.

Open Access Original Research Article

The Antiangiogenic Effects of Tamoxifen might be Attributed to Receptor Binding Capacity of its Solvent Dimethylsulfoxide in Breast Cancer: A Molecular Docking Study

Orhan Koçak, Nazlı Deniz Taşkın, Ece Şimşek

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/jpri/2019/v30i230265

Aim: Tamoxifen, a Dimethyl sulfoxide (DMSO)-soluble chemotherapeutic, is widely used in the treatment of breast cancer. Tamoxifen has an anti-angiogenic effect especially on breast tumor cells by blocking VEGF(Vascular Endothelial Growth Factor) production. On the other hand, according to our previously studies, we demonstrated that DMSO could mimics the cytotoxic effects of Thalidomide in 4T1 mouse breast cancer cells and is related with the anti-angiogenic response of HeLa cells. At this point of view, the aim of this study was to determine the possible binding effects of DMSO on certain cell surface receptors.

Methods: The in silico studies were implemented using the Docking Server. X-ray structures of receptor proteins’ PDB files were obtained from Protein Data Bank [Human Progesteron Receptor (PDB ID: 1A28, Human Tumor Necrosis Factor Receptor-1 (PDB ID: 1EXT), Human Interferon Gamma Receptor-1 (PDB ID: 1FG9), Human Epidermal Growth Factor Receptor (PDB ID: 1IVO)]. Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method.

Results: According to the molecular docking results of this study, DMSO, the general solvent of Tamoxifen, has a 90% binding capacity to the Interferon Gamma (IFNɣ) receptor and 100% to Tumor Necrosis Factor alfa (TNFα) receptor, respectively.

Conclusion: These receptors have significant effects on the proliferation and angiogenesis of cancer cells which leads to the metastasis of breast cancer. In conclusion, the antiangiogenic effects of Tamoxifen might be reduced due to its solvent DMSO's angiogenic effects.

Open Access Original Research Article

Determination of the Effect of High-Dose Intralipid in Compared to Its Gradual Dose in Very Low Birth Weight Newborns: A Case-control Study

Mandana Kashaki, Arash Bordbar, Ali Mazouri, Nikta Nikbakht, Babak Jafarvand

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/jpri/2019/v30i230267

Objective: The aim of this study was to determine the effect of high dose intralipid in compared to its gradual dose in very low birth weight newborns in Iran. 

Methods: This study was a case-control study that conducted on 104 very low birth weight infants (<1500 g) referred to Akbarabadi hospital of Tehran (Iran) in 2016. The infants were randomly assigned to two groups (case group: 52 vs. control group: 52). The control group received intralipid 20% with a dose of 1 g/kg/24 h in the first and second day of the study, then from 3rd day to 3 g/kg /24h was raised. But, the case group received 3 g/kg/24 h of intralipid 20% from the first day and continued until the end of the study. In both groups, the study lasted for up to 30 days. Data were collected and analyzed using SPSS22 software. Also P-Value <0.05 was considered as a significant level.

Results: The results showed mean daily weight gain in case group is higher than control group and this difference was significant statistically (P-Value < 0.05). Also, although the mean of blood sugar, triglyceride, HCO3, the number of positive blood culture and the number of positive CPR in case group were higher than control group, but these differences were not statistically significant (P-Value >0.05).

Conclusion: Given that the better and faster growth of newborns in the intralipid group with high-dose in compared to intralipid group with gradual dose, the use of higher initial doses is recommended in newborns with very low birth weight.

Open Access Review Article

Drosophila melanogaster: A Veritable Genetic Tool and in vivo Model for Human Alzheimer’s Disease

Oluwatosin Imoleayo, Oyeniran

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/jpri/2019/v30i230264

The rise in the cases of neurodegenerative diseases, such as the familial forms of Alzheimer’s disease is worrisome and a burden to many societies in our ever-increasing world. Due to the complexity in the nature of the brain and spinal cord characterized by an extremely organized network of neuronal cells, there is a need to answer scientific inquiries in uncomplicated, though similar, systems. Drosophila melanogaster (fruit-fly) is a well-studied and easily managed genetic model organism used for discerning the molecular mechanisms of many human diseases. There are strong conservations of several basic biological, physiological and neurological features between D. melanogaster and mammals, as about 75% of all human disease-causing genes are considered to possess a functional homolog in the fruit-fly. The development of Drosophila models of several neurodegenerative disorders via developed transgenic technologies has presented spectacular similarities to human diseases. An advantage that the fruit-fly has over other model organisms, such as the mouse, is its comparatively brief lifespan, which allows complex inquiries about brain functions to be addressed more quickly. Furthermore, there have been steady increases in understanding the pathophysiological basis of many neurological disorders via genetic screenings with the aid of Drosophila models. This review presents a widespread summary of the fruit-fly models relevant to Alzheimer’s disease, and highlight important genetic modifiers that have been recognized using this model.

Open Access Review Article

A Review on Novel Progressions in Intravenous (IV) agents for Anesthesia

Babak Hosseinzadeh Zoroufchi, Abolfazl Abdollahpour

Journal of Pharmaceutical Research International, Page 1-13
DOI: 10.9734/jpri/2019/v30i230266

One of the main medical proficiencies involved with the procedure of patient’s perioperative care before, during and after operation is anesthesiology. This field of science has made a lot of hopeful progression in detection of new, secure, impressive, and productive procedures for proper management of patients. The most effective sedative–hypnotic agents which categorized in titratable intravenous medication, have highest medicinal effect and the least side effects. Currently a high effort is employed for developing such drugs with central focus on improving the available drugs structures for modifying their pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. Various drugs are investigating for achieving more progression which includes etomidate, midazolam analogues, and diprivan. One of the main approaches for investigating about the development of anesthesia agents is swift screening of related libraries of molecular structure which evaluate phenotypic or structural assays of anesthetic and receptor interactions of agents. Due to the recently high demands of clinical operations for more sufficient anesthesia agents, the progression of anesthetic agents is experiencing a new generation of advanced clinical trials. In this regard, the current study is trying to provide a brief look on the newest anesthetic drugs and novel developed procedures which simplify this objective. This comprehensive study reviews would clarify the novel technology of progression of drugs which do not have physical addiction effects, distinctive system of anesthetic drug delivery, and the novel failures of drugs and their facilities.