Beneficial effect of 5-HT1b/1d agonist on Parkinson's disease by modulating glutamate and reducing deposition of α-synuclein.

The given investigation examined the neuroprotection role of 5-HT1b/1d agonist in reserpine induced Parkinson's disease (PD) in male Wistar rats. PD was induced in rats by reserpine at 5 mg/kg ip for 3 days and thereafter the rats were provided with the following treatments for 4 days, zolmitriptan (ZLM) group (30 mg/kg ip); STD group (levodopa + carbidopa, 200 + 5 mg/kg ip); ZLM + GA group (zolmitriptan, 30 mg/kg ip and glutamic acid, 1.5 mg/kg); ZLM + DX group (zolmitriptan, 30 mg/kg ip and dextromethorphan, 20 mg/kg ip). All the groups were then assessed for cognitive and motor functions at the end of the protocol. Moreover, oxidative stress parameters and histopathological changes were observed in rats of all treatment groups. Deposition of α-synuclein in the brain tissue was observed by silver staining. Data of this investigation revealed that motor and cognitive functions were improved in the ZLM-treated group compared with the negative control group, which was observed to be reversed in ZLM + GA group. Treatment with ZLM ameliorated oxidative stress and histopathological changes in the brain tissue of PD rats. Further, ZLM reduced the deposition of α-synuclein in PD rats, which reversed in ZLM + GA-treated group. This study concludes by stating that 5-HT1b/1d agonist can prevent neurodegeneration and reduce oxidative stress in PD rats. The probable underlying mechanism of such an effect of 5-HT1b/1d agonist could be by regulating the deposition of α-synuclein and reducing the expression of NMDA receptor.

Self-reported and the actual involvement of community pharmacy professionals in the management of acute childhood diarrhea in Jazan Province, Saudi Arabia: Simulated patient visits and survey study.

Background: Acute childhood diarrhea is one of the most common causes of dehydration, and if severe, can potentially lead to death as well. The present study was aimed at evaluating the knowledge and attitudes of community pharmacy professionals towards the management of acute childhood diarrhea and comparing them with their actual practices in Jazan Province, Kingdom of Saudi Arabia (K.S.A). Methods: Simulated patient visits and a cross-sectional survey making use of a 27-item self-report questionnaire were conducted amongst a sample of 303 community pharmacy professionals (51.2 % male and 48.8 % female) with an age range of 25-56 years, between August 1 and December 1, 2021, in Jazan Province, Saudi Arabia. Convenience sampling technique was used for the recruitment of the participants. Results: Significant positive correlations were seen between knowledge score (self-report survey) and practice score (simulated patient visit) regarding patients' history taking (r = 0.65; p < 0.01), drug recommendations (r = 0.71; p < 0.01) and providing information regarding food and fluid intake (r = 0.44; p < 0.01). The alpha coefficients for all the items of the survey instrument were noted to be greater than (or) equal to the 0.70 threshold for almost all sections, hence indicating good reliability and internal consistency of the developed scale. Conclusion: In the present study, even though we observed improved participants' performance during the self report survey, their performance level greatly dropped in actual practice. This warrants for a need for educational programs to improve their actual dispensing practices. The present study has also shown simulated patient visits to be a reliable, simple and a robust method of assessing the actual dispensing practices of community pharmacy professionals.

Awareness and Preparedness of COVID-19 Outbreak Among Healthcare Workers and Other Residents of South-West Saudi Arabia: A Cross-Sectional Survey.

Background: Coronavirus disease-2019 (COVID-19) was declared a "pandemic" by the World Health Organization (WHO) in early March 2020. Globally, extraordinary measures are being adopted to combat the formidable spread of the ongoing outbreak. Under such conditions, people's adherence to preventive measures is greatly affected by their awareness of the disease. Aim: This study was aimed to assess the level of awareness and preparedness to fight against COVID-19 among the healthcare workers (HCWs) and other residents of the South-West Saudi Arabia. Methods: A community-based, cross-sectional survey was conducted using a self-developed structured questionnaire that was randomly distributed online among HCWs and other residents (age ≥ 12 years) of South-West Saudi Arabia for feedback. The collected data were analyzed using Stata 15 statistical software. Results: Among 1,000 participants, 36.7% were HCWs, 53.9% were female, and 44.1% were aged ≥ 30 years. Majority of respondents showed awareness of COVID-19 (98.7%) as a deadly, contagious, and life-threatening disease (99.6%) that is transmitted through human-to-human contact (97.7%). They were familiar with the associated symptoms and common causes of COVID-19. Health organizations were chosen as the most reliable source of information by majority of the participants (89.6%). Hand hygiene (92.7%) and social distancing (92.3%) were the most common preventive measures taken by respondents that were followed by avoiding traveling (86.9%) to an infected area or country and wearing face masks (86.5%). Significant proportions of HCWs (P < 0.05) and more educated participants (P < 0.05) showed considerable knowledge of the disease, and all respondents displayed good preparedness for the prevention and control of COVID-19. Age, gender, and area were non-significant predictors of COVID-19 awareness. Conclusion: As the global threat of COVID-19 continues to emerge, it is critical to improve the awareness and preparedness of the targeted community members, especially the less educated ones. Educational interventions are urgently needed to reach the targeted residents beyond borders and further measures are warranted. The outcome of this study highlighted a growing need for the adoption of innovative local strategies to improve awareness in general population related to COVID-19 and its preventative practices in order to meet its elimination goals.

In vivo assessment of genotoxic potential of brown shammah (smokeless tobacco) in bone marrow cells of mice.

This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo.

Evaluation of mutagenic and anti-mutagenic potential of alpha-lipoic acid by chromosomal aberration assay in mice.

This study investigated both the mutagenicity and anti-mutagenicity of alpha-lipoic acid (ALA) in the bone marrow cells of mice using a chromosomal aberration assay. Cyclophosphamide (CP) 40 mg/kg was used as a clastogen in the positive control, and a vehicle-treated negative control group was also included. Multiple dose levels (15, 30, and 100 mg/kg of ALA) were given by intraperitoneal injection (IP) alone and in combination with CP (CP was administered 1 h prior to ALA). Bone marrow samples were collected 12 and 24 h after drug administration. The results demonstrated a significant increase in the frequency of chromosomal aberrations (CA) in bone marrow cells with depressions in the mitotic index (MI) of the positive control group of mice. However, in the groups of mice treated with different doses of ALA in the presence of CP, the percentages of CA decreased significantly with increases in mitotic activity. The results also indicate that ALA given alone in different doses had no mutagenic effect on mouse bone marrow cells. ALA has a dose and time-dependent protective effect against the mutagenicity induced by CP.

The genotoxic and cytotoxic effects of nimesulide in the mouse bone marrow.

Genotoxicity of nimesulide (NM) was evaluated by employing bone marrow (BM) chromosomal aberration (CA) and micronucleus assays in Swiss albino mice. For BM CA assay, mice of either sex were treated orally with 1.5, 2.5 and 5 mg body weight solution of NM in 0.2 mL of 0.05% CMC (carboxy methyl cellulose) daily for 4, 13, 28 and 40 weeks. Treatment induced dose-dependent and significantly depressed mitotic activity and increase in CAs per cell in the BM cells after 13 weeks of treatment at all dose levels. In micronucleus assay, male mice were treated orally with the same dose levels and sampling durations as for CA assay. Treatment increased the percentage of micronucleated polychromatic erythrocytes frequency and showed a statistically significant reduction in polychromatic erythrocyte/normochromatic erythrocyte ratio, as compared to control groups. Cyclophosphamide (40 mg/kg) was used as clastogen (positive control) and yielded the expected positive results. Cytotoxicity was observed in the 8-week recovery period after 40 weeks of dosing, but it was not significant. On the basis of these findings, it may be concluded that in the long term, NM, or its biotransformed product, is genotoxic and cytotoxic for BM cells of mice in vivo.

Investigation of antigenotoxic potential of Syzygium cumini extract (SCE) on cyclophosphamide-induced genotoxicity and oxidative stress in mice.

The present study investigated the protective effects of Syzygium cumini extract (SCE; 100 and 200 mg/kg) against genotoxicity and oxidative stress (OS) induced by cyclophosphamide (CP) in mice. Animals were received 14 days pretreatment (oral) of SCE, followed by induction of genotoxicity by CP (40 mg/kg), 24 hours before sacrifice. Mice bone marrow chromosomal aberration assay, micronucleus assay, and sperm abnormality assay were employed for the study. Activities of hepatic antioxidant enzymes were also investigated. Phytochemical investigation was done to determine total phenolic and flavonoid content in SCE. Results showed that CP produced a significant increase in average percentage of aberrant metaphases and chromosomal aberrations (CAs) excluding gap, and micronuclei (MN) formation in polychromatic erythrocytes produced cytotoxicity in mouse bone marrow cells and induced abnormal sperms in a male germ line. CP also markedly inhibited the activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutahione (GSH) and increased malondialdehyde (MDA) content. Pretreatments with SCE significantly inhibited the frequencies of aberrant metaphases, CAs, MN formation, and cytotoxicity in mouse bone marrow cells induced by CP. SCE also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. Total phenolic content present in SCE was 24.68%, whereas total flavonoids were calculated as 3.80%. SCE has a protective effect against genotoxicity and OS induced by CP.

Investigation of antimutagenic potential of Foeniculum vulgare essential oil on cyclophosphamide induced genotoxicity and oxidative stress in mice.

The present study investigated the protective effects of Foeniculum vulgare (fennel) essential oil (FEO) against genotoxicity induced by cyclophosphamide (CP). Mice bone marrow chromosomal aberration (CA), micronucleus, and sperm abnormality assays were employed to measure genotoxicity and cytotoxicity, respectively. The activities of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) content in the liver were also investigated spectrophotometrically. Animals were administered two different doses of FEO (1 and 2 mL/kg) continuously for 3 days at intervals of 24 hours by the oral route before tissue sampling. The results showed that CP produced a significant increase in the average percentage of aberrant metaphases and CAs, excluding gap and micronuclei formation in polychromatic erythrocytes (PCEs), produced cytotoxicity in mouse bone marrow cells, and induced abnormal sperms in the male germ line. CP also markedly inhibited the activities of SOD, CAT, and GSH and increased MDA content. Pretreatments with FEO significantly inhibited the frequencies of aberrant metaphases, CAs, micronuclei formation, and cytotoxicity in mouse bone marrow cells induced by CP and also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. FEO inhibits genotoxicity and oxidative stress induced by CP.

Genotoxicity of ibuprofen in mouse bone marrow cells in vivo.

Genotoxicity of ibuprofen was evaluated by employing the mouse in vivo chromosomal aberration (CA) test. Ibuprofen administered orally at doses of 10, 20, 40, and 60 mg/kg body weight to mice resulted in mitotic depression and induction of CAs. A dose-related decrease in mitotic index (MI) and an increase in the frequencies of chromosomal aberrations per cell (CAs/cell) were recorded in bone marrow cells. However, a statistically significant reduction in MI and an increase in CAs/cell were found for both the higher doses. The results obtained indicate that ibuprofen is capable of inducing dose-dependent genotoxicity in bone marrow cells of mice.