Incorporation of methotrexate into coconut oil nanoemulsion potentiates its antiproliferation activity and attenuates its oxidative stress.

Methotrexate (MTX), a chemotherapeutic agent, has limited clinical applications due to its pulmonary and neurotoxicity. The antineoplastic activity of MTX-NE COCO, which is MTX formulated in coconut oil nanoemulsion (NE), was evaluated in A549 non-small cell lung cancer cells while its adverse side effects on the oxidative stress of the lung and brain were assessed in mice. The z-average diameter for the dispersed nanodroplet of MTX-NE COCO (79.74 ± 3.49 nm) was considerably greater than the free-NE COCO (64.80 ± 3.34 nm). In contrast, the magnitude of the negative z-potential of MTX-NE COCO (3.00 ± 0.69 mV) was markedly less than that of free-NE COCO (8.20 ± 0.76 mV). The minimum inhibitory concentration (IC50) of MTX-NE COCO (18 ± 1.8 µM) was less than the IC50 of free MTX (32 ± 1.2 µM) by around twofold. The in vivo evaluation of the MTX-NE COCO treatment revealed that the antioxidant enzymes activities of the brain and lung tissues, catalase, superoxide dismutase, and glutathione reductase, were relatively raised while the malondialdehyde amount was diminished when compared to the free MTX treatment. In conclusion, combining MTX with coconut oil in a NE had improved its efficacy while ameliorating its oxidative stress effect on the brain and lungs.

Coconut oil nanoemulsion attenuates methotrexate-induced hepatotoxicity and nephrotoxicity in Ehrlich ascites carcinoma-bearing mice

Objective: To evaluate the protective effect of the coconut oil nanoemulsion against methotrexate-induced hepatotoxicity and nephrotoxicity in Ehrlich ascites carcinoma-bearing Swiss albino mice. Methods: Forty mice were divided into four groups. Group Ⅰ served as the untreated Ehrlich ascites carcinoma-bearing mice while Ehrlich ascites carcinoma-bearing mice in groups Ⅱ–Ⅳ received an intraperitoneal injection of 0.2 mL/kg coconut oil nanoemulsion, 20 mg/kg methotrexate as well as 0.2 mL/kg coconut oil nanoemulsion mixed with 20 mg/kg methotrexate, respectively. The toxicities of the treatments were assessed by determining the complete blood count, performing the serum analysis for liver and kidney functions, evaluating the oxidative status and visualizing histological changes in the liver and kidney tissues. Results: Treatment with methotrexate and coconut oil nanoemulsion markedly diminished the liver parameters including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, direct bilirubin and total bilirubin which were raised by methotrexate treatment (P < 0.05). Similarly, creatinine and blood urea nitrogen, as the indicators of kidney function, were dramatically lowered in the combination treatment group compared to the methotrexate group (P < 0.05). In addition, treatment with methotrexate and coconut oil nanoemulsion reduced the malondialdehyde and increased catalase, glutathione reductase and superoxide dismutase, in the liver and kidney tissues (P < 0.05). The treatment with methotrexate and coconut oil nanoemulsion reduced white blood cell count and increased the hemoglobin amount (P < 0.05), but did not cause any change in platelets and red blood cell count. Conclusions: Coconut oil nanoemulsion as a nanocarrier has great potential in reducing the adverse side effects induced by methotrexate.

Osteoporosis knowledge and awareness among university students in Saudi Arabia.

Awareness and knowledge about any disease is the first step to prevent and treat it, so this study evaluates osteoporosis awareness and knowledge in university students. Our results showed a high awareness and good knowledge of osteoporosis. Females were better informed than males. Knowledge increased with increasing education level. PURPOSE: Osteoporosis is a worldwide health problem, including Saudi Arabia where vitamin D deficiency is common. Prevention of osteoporosis must begin by increasing awareness of the disease from a young age. This study aimed to assess awareness and knowledge of osteoporosis among young adults (18-30 years) attending Saudi universities, exploring the relationship between education and gender and the sources of information in this age group. METHODS: A cross-sectional survey was conducted in 337 students (176 females; 161 males) randomly selected from four Saudi universities during January-December 2017. Education level ranged from preparatory year to undergraduate and postgraduate levels. A self-reported questionnaire was designed to assess awareness and knowledge of osteoporosis across several domains, including risk factors for the disease, prevalence, symptoms, prevention, and treatment. RESULTS: Overall, 92% of students had some awareness of osteoporosis through a variety of sources, predominantly via friends. Just over half of all students had a good or high knowledge level overall (53.4 ± 16.6%). Knowledge score correlated with education (r2 = 0.28) and gender (r2 = 0.27); p < 0.0001. Females were better informed than males (57.7 ± 15.4% vs 48.8 ± 16.8%; p < 0.0001). Knowledge increased with increasing education level (preparatory year (47.8 ± 15.3%), undergraduate (53.5 ± 16.5%), and postgraduate (61.8 ± 15.8%); all p < 0.0001). CONCLUSION: Knowledge of osteoporosis was good among university students in Saudi Arabia, higher in females and with increasing years of education. Overall, students were more knowledgeable about risk factors compared to other aspects such as symptoms, prevention, or treatment of osteoporosis.

In Vivo Evaluation of the Anticancer Activity of the Gemcitabine and Doxorubicin Combined in a Nanoemulsion.

CONTEXT: Doxorubicin (DOX) and gemcitabine (GEM) are anticancer drugs that were combined in a nanoemulsion (NE) to reduce their adverse side effects. AIM: To detect the antitumor activity of the combination formulas of GEM and DOX, loaded either in water (GEM+DOX-Sol) or in NEs (GEM-DOX combination/loaded NE [GEM+DOX/LNE]), in female Swiss albino mice inoculated with Ehrlich ascites carcinoma (EAC). SETTINGS AND DESIGN: The anticancer assessment of the NE formulas was implemented in 200 mice, which were divided into 10 groups. MATERIALS AND METHODS: It includes the detection of the change in body weight, analysis of the hematological and serum biochemical profiles, and study of the histopathologic alterations of the heart tissues. STATISTICAL ANALYSIS: One-factor analysis of variance was used. RESULTS: Mice treated with GEM + DOX/LNE, which have an z-average of 155.38±2.33nm and zeta potential of -38.5±1.3 mV, recorded a considerable improvement in the mean survival time (MST), which was 60 days, as compared to the EAC control group, which has an MST of 28 days. It also restored the hematological and serum biochemical parameters toward normal values. CONCLUSIONS: The combination of GEM and DOX in NE has significantly diminished the cardiotoxicity of DOX and hematotoxicity of GEM while improving their antitumor properties.

Protective effect of melatonin against zonisamide-induced reproductive disorders in male rats.

INTRODUCTION: Zonisamide (ZNS) is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. The pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone (LH) surge. The aim of the present work was to study the protective effect of melatonin against the potential suppression impact of ZNS on reproductive activity. MATERIAL AND METHODS: Ninety adult albino male rats were allocated to several groups treated with melatonin (10 mg/kg BW), ZNS (10, 20 and 50 mg/kg BW) and 10 mg/kg of melatonin plus ZNS (10, 20 or 50 mg/kg BW, respectively). Reproductive hormones (testosterone, LH and follicle-stimulating hormone (FSH)) levels were measured in animal serum. Sperm abnormalities and DNA fragmentation in testis tissues as well as expression alteration of several reproductive-related genes were analyzed. RESULTS: The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats. In addition, ZNS treatment increased the sperm abnormalities and DNA fragmentation and inducible nitric oxide synthase (iNOS) in testis tissues as well as GABA level in liver tissues. However, melatonin supplementation inhibited the negative symptoms of ZNS in which it increased the levels of reproductive hormones and expression of their encoding genes in the ZNS-treated rats. Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats. CONCLUSIONS: The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.

Effect of melittin on mice stomach.

Melittin, the main bee venom component, has many positive biological effects and a relatively low toxicity in various cell types. However, there is no evidence of the effect of melittin on gastrointestinal cells. In the present study, we investigated the histological and immuonohistochemical effects of melittin on mice stomach. Adult male mice (Albino Swiss) were randomly divided into two groups (7 mice for each group): control group and melittin only treated group (10 and 40 µg/kg). These mice were sacrificed, then samples from the stomach were collected and prepared for histopathological studies by using alcian blue stain and immuonohistochemical studies by using smooth muscle actin (SMA) antibody. Treatment with melittin alone do not cause any harmful effect on the stomach tissue where the microscopic examination of Alcian blue stained section showed the normal distribution of the mucous secreting cells of the stomach tissues. On other hand, no changes were observed on smooth muscle cells. This study demonstrated the safety of using melittin on gastrointestinal tissues if used in definite dose and for suitable duration, which offers an opportunity for its use as a treatment for many diseases of the gastrointestinal tract.

Neuronal activation and plasticity in Schistosoma mansoni infected mice.

Schistosomiasis leads to structural and functional changes which may result from unbalanced release of some inflammatory mediators. The aim of the study was to investigate the effect of intestinal parasitic infection on nitric oxide release and to evaluate the neural plasticity that leads to motility disturbance. Experiments were performed in Swiss mice 8- and 12-weeks following infection with Schistosoma mansoni compared to untreated controls. Jejunal motility was assessed using a Trendelenburg preparation to study aboral directed peristaltic pressure waves. Histological examination was used to determine the pathological characteristics of inflammation. Parasitic infection produces diffuse inflammatory infiltrate in both 8- and 12-weeks infected animals. Inflammation had significant effect on peristaltic pressure waves amplitude and intervals at 8-weeks compared to control; whereas, in 12-weeks post infection there was a significant decrease in peristaltic pressure waves amplitude and interval compared to 8- weeks and control. Nitric oxide synthase inhibitor (L-NAME 100 µM) induced a significant increase in amplitude and decrease in intervals in control, 8- and 12- weeks infected animals. In conclusion, parasitic infection leads to disturbance in the release of the inflammatory mediators. This study indicated the role of nitric oxide in developing granulomatous inflammation and participating in motility disturbance.

Somatostatin sst(2) receptors inhibit peristalsis in the rat and mouse jejunum.

Somatostatin [somatotropin release-inhibitory factor (SRIF)] has widespread actions throughout the gastrointestinal tract, but the receptor mechanisms involved are not fully characterized. We have examined the effect of selective SRIF-receptor ligands on intestinal peristalsis by studying migrating motor complexes (MMCs) in isolated segments of jejunum from rats, mice, and sst(2)-receptor knockout mice. MMCs were recorded in 4- to 5-cm segments of jejunum mounted horizontally in vitro. MMCs occurred in rat and mouse jejunum with intervals of 104.4 +/- 10 and 131.2 +/- 8 s, respectively. SRIF, octreotide, and BIM-23027 increased the interval between MMCs, an effect fully or partially antagonized by the sst(2)-receptor antagonist Cyanamid154806. A non-sst(2) receptor-mediated component was evident in mouse as confirmed by the observation of an inhibitory action of SRIF in sst(2) knockout tissue. Blocking nitric oxide generation abolished the response to SRIF in rat but not mouse jejunum. sst(2) Receptors mediate inhibition of peristalsis in both rat and mouse jejunum, but a non-sst(2) component also exists in the mouse. Nitrergic mechanisms are differentially involved in rat and mouse jejunum.