Evaluation of the safety and antioxidant activities of Crocus sativus and Propolis ethanolic extracts

AbstractThe possible toxicological effects and in vitro antioxidant activity of the ethanolic extracts of Crocus sativus and Propolis were investigated. Both extracts did not cause any mortalities or signs of toxicity in mice when administered orally at doses up to 5g/kgb.wt. In the sub-chronic study; the tested extracts did not produce any significant change in liver and kidney functions of rats, following oral administration for 8 successive weeks at doses of 500mg/kgb.wt. of each. Propolis showed remarkable in vitro antioxidant activity at concentrations of (40–100mg/ml). In contrast, the ethanolic extract of C. sativus ethanolic extract showed weak antioxidant activity in concentrations of (1–10mg/ml) while at concentrations of (20–100mg/ml) failed to exhibit any antioxidant activity. It was concluded that: both extracts were non-toxic, as they did not cause any mortalities or signs of toxicity in mice when administered orally at doses up to 5g/kgb.wt. Daily oral administration of C. sativus, Propolis ethanolic extracts alone or in combination for 8 successive weeks to rats was quiet safe and didn't cause any toxic changes in liver and kidney. Antioxidant study showed that Propolis ethanolic extract was a more potent antioxidant than C. sativus extract

Antioxidant and hepatoprotective effects of Astragalus echinops and Astragalus logopodioides ethanolic extracts on paracetamol-induced liver injury in rats

Background: Paracetamol (PCM) has an adequate safety profile when taken in normal doses. However, it could produce oxidative stress with liver injury when taken in an overdose. Plants of Astragalus genus (F. Fabaceae) are of wide-spread applications. Astragalus echinops (A. echinops) and Astragalus logopodioides (A. logopodioides) were tested for their potential hepatoprotective activities against liver injury induced by PCM in rats.Material and Methods: Seven groups of rats were used for determination of hepatoprotective activities of the extracts. The normal and hepatotoxic control groups received the vehicle while other groups were treated with silymarin (100 mg/ kg), A. echinops (250 and 500 mg/kg) and A. logopodioides (250 and 500 mg/ kg), respectively for seven days. Liver injury was induced on the 5th day by oral dosing of PCM (2g/kg) to all rats except those in normal control group. Moreover, the in vitro antioxidant activities of A. echinops and A. logopodioides extracts were tested using 2,2- diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging.Results: Hepatic enzyme markers as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glutamyl transferase and level of total bilirubin were significantly elevated, while total protein and albumin were declined significantly in PCM-exposed animals. The liver antioxidant markers like the activities of superoxide dismutase, catalase and glutathione peroxidase and the levels of reduced glutathione were significantly declined, while hepatic malondialdehyde levels were significantly increased in PCM alone-treated rats. Administration of A. echinops (250 and 500 mg/kg) and A. logopodioides (500 mg/ kg) extracts prior to PCM, significantly protected against the elevation in the serum activities of hepatic enzymes and bilirubin and reduced oxidative stress. The hepatoprotective effect of both extracts was further confirmed by histological findings in the liver tissue. In addition, both extracts displayed in vitro antioxidant activities in a concentration-dependent way.Conclusion: Our results suggest that both extracts protect the liver against oxidative damage and they could be used as effective hepatoprotectives against PCM induced liver injury.Keywords: Astragalus, Paracetamol, Hepatotoxicity, Hepatoprotective, DPPH, Antioxidan

ANTIOXIDANT AND HEPATOPROTECTIVE EFFECTS OF ASTRAGALUS ECHINOPS AND ASTRAGALUS LOGOPODIOIDES ETHANOLIC EXTRACTS ON PARACETAMOL-INDUCED LIVER INJURY IN RATS

Background: Paracetamol (PCM) has an adequate safety profile when taken in normal doses. However, it could produce oxidative stress with liver injury when taken in an overdose. Plants of Astragalus genus (F. Fabaceae) are of wide-spread applications. Astragalus echinops (A. echinops) and Astragalus logopodioides (A. logopodioides) were tested for their potential hepatoprotective activities against liver injury induced by PCM in rats. Material and Methods: Seven groups of rats were used for determination of hepatoprotective activities of the extracts. The normal and hepatotoxic control groups received the vehicle while other groups were treated with silymarin (100 mg/ kg), A. echinops (250 and 500 mg/kg) and A. logopodioides (250 and 500 mg/ kg), respectively for seven days. Liver injury was induced on the 5th day by oral dosing of PCM (2g/kg) to all rats except those in normal control group. Moreover, the in vitro antioxidant activities of A. echinops and A. logopodioides extracts were tested using 2,2- diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging. Results: Hepatic enzyme markers as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glutamyl transferase and level of total bilirubin were significantly elevated, while total protein and albumin were declined significantly in PCM-exposed animals. The liver antioxidant markers like the activities of superoxide dismutase, catalase and glutathione peroxidase and the levels of reduced glutathione were significantly declined, while hepatic malondialdehyde levels were significantly increased in PCM alone-treated rats. Administration of A. echinops (250 and 500 mg/kg) and A. logopodioides (500 mg/ kg) extracts prior to PCM, significantly protected against the elevation in the serum activities of hepatic enzymes and bilirubin and reduced oxidative stress. The hepatoprotective effect of both extracts was further confirmed by histological findings in the liver tissue. In addition, both extracts displayed in vitro antioxidant activities in a concentration-dependent way. Conclusion: Our results suggest that both extracts protect the liver against oxidative damage and they could be used as effective hepatoprotectives against PCM induced liver injury

Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats

This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive), using N(G)-nitro-L-arginine-methyl ester- (L-NAME-) induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally) for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks) resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO), and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE) and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS) gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence

TOXICOLOGICAL AND PHARMACOLOGICAL ASSESSMENT OF GOLD NANORODS IN NORMAL RATS

Objective: assessment of acute, subchronic and chronic toxicity of pegylated gold nanorods (PEG-gold NRs) in Wistar rats of both sex in three routes of administration {intravenous (IV), intramuscular (IM) and subcutaneous (SC)}.Methods: in the acute toxicity study; PEG-gold NRs were injected once by three different routes, blood and tissue samples were collected after 14 d. In the subchronic and chronic studies; PEG-gold NRs were injected via three different routes, at 0.225, 0.45 and 0.9 mg/kg, once daily for 5 consecutive days, followed by a 23-day recovery period, for three and six months in the subchronic and chronic toxicity studies, respectively. Hematology, urinalysis, biochemical and histopathological examinations were conducted at the end of each study.Results: acute toxicity showed a significant decrease in serum triglycerides and cholesterol levels after single IV, IM and SC injection of PEG-gold NRs, while serum creatinine was significantly increased after IV and IM injection. Subchronic results revealed a significant decrease in serum triglycerides and cholesterol levels. The chronic study showed a significant decrease in serum triglycerides, sodium levels, total leukocytes count and significant increase in serum creatinine after IV injection. IM injection resulted in significant decrease in serum alkaline phosphatase, triglycerides, cholesterol, sodium levels and total leukocytes count. SC injection resulted in significant decrease in serum triglycerides, glucose, red blood cell count with increased creatinine and hematocrit.Conclusion: PEG-gold NRs at the three examined doses is apparently safe since no serious signs of toxicity were detected. IM and SC routes of injection were irritating, so we recommend the IV route.Â

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% 10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% 5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million 6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million 2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million 1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million 67.7-90.8] DALYs or 55.5% 48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million 22.3-48.6] DALYs or 24.3% 15.7-33.2]), high fasting plasma glucose (28.9 million 19.8-41.5] DALYs or 20.2% 13.8-29.1]), ambient particulate matter pollution (28.7 million 23.4-33.4] DALYs or 20.1% 16.6-23.0]), and smoking (25.3 million 22.6-28.2] DALYs or 17.6% 16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Combined hepatoprotective and antidepressant effects of resveratrol in an acute model of depression

There are numerous herbal medicines that have been introduced into psychiatric practice because of greater compliance and milder side effects. Polygonum cuspidatum is a native Asian plant; known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders, such as psychosocial stress, dementia and Parkinson’s disease. Resveratrol is the active ingredient of P. cuspidatum. Researchers have suggested that the trans-isomer of resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, hepatic and neuroprotective properties. In this study we examined the hepatoprotective and antidepressant effects of trans-resveratrol against fluoxetine in an acute reserpine model of depression in rats. Main methods: depression-like behaviors were induced by single reserpine intraperitoneal injection (6 mg/kg, i.p.). Trans-resveratrol (15, 30 and 60 mg/kg bwt) and fluoxetine (24 mg/kg bwt) were administered orally for the following 3 days. Behavioral effects namely open field test (OFT) and forced swimming test (FST) and biochemical parameters namely neurotransmitters levels and antioxidant contents were assessed. Liver histopathological examination was performed. Key findings: Results revealed that resveratrol (60 mg/kg bwt) showed a potential hepatoprotective and an antidepressant-like effects compared to those of fluoxetine