The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients.

PURPOSE: To investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. MATERIALS/METHODS: 76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. RESULTS: Among these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. CONCLUSION: The study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

Anti-Fibrotic Efficacy of Apigenin in a Mice Model of Carbon Tetrachloride-Induced Hepatic Fibrosis by Modulation of Oxidative Stress, Inflammation, and Fibrogenesis: A Preclinical Study.

BACKGROUND: Hepatic fibrosis is a major health problem all over the world, and there is no effective treatment to cure it. Hence, the current study sought to assess the anti-fibrotic efficacy of apigenin against CCl4-induced hepatic fibrosis in mice. METHODS: Forty-eight mice were put into six groups. G1: Normal Control, G2: CCl4 Control, G3: Silymarin (100 mg/kg), G4 and G5: Apigenin (2 &20 mg/Kg), G6: Apigenin alone (20 mg/Kg). Groups 2, 3, 4, and 5 were given CCl4 (0.5 mL/kg. i.p.) twice/week for six weeks. The level of AST, ALT, TC, TG, and TB in serum and IL-1ß, IL-6, and TNF-α in tissue homogenates were assessed. Histological studies by H&E staining and Immunostaining of liver tissues were also performed. RESULTS: The CCl4-challenged group showed increased serum AST (4-fold), ALT (6-fold), and TB (5-fold). Both silymarin and apigenin treatments significantly improved these hepatic biomarkers. The CCl4-challenged group showed reduced levels of CAT (89%), GSH (53%), and increased MDA (3-fold). Both silymarin and apigenin treatments significantly altered these oxidative markers in tissue homogenates. The CCl4-treated group showed a two-fold increase in IL-1ß, IL-6, and TNF-α levels. Silymarin and apigenin treatment considerably decreased the IL-1ß, IL-6, and TNF-α levels. Apigenin treatment inhibited angiogenic activity, as evidenced by a decrease in VEGF (vascular endothelial growth factor) expression in liver tissues, and a decline in vascular endothelial cell antigen expression (CD34). CONCLUSIONS: Finally, these data collectively imply that apigenin may have antifibrotic properties, which may be explained by its anti-inflammatory, antioxidant, and antiangiogenic activities.

Detection of Adverse Drug Reactions in COVID-19 Hospitalized Patients in Saudi Arabia: A Retrospective Study by ADR Prompt Indicators.

Seeking an alternative approach for detecting adverse drug reactions (ADRs) in coronavirus patients (COVID-19) and enhancing drug safety, a retrospective study of six months was conducted utilizing an electronic medical record (EMR) database to detect ADRs in hospitalized patients for COVID-19, using "ADR prompt indicators" (APIs). Consequently, confirmed ADRs were subjected to multifaceted analyses, such as demographic attribution, relationship with specific drugs and implication for organs and systems of the body, incidence rate, type, severity, and preventability of ADR. The incidence rate of ADRs is 37%, the predisposition of organs and systems to ADR is observed remarkably in the hepatobiliary and gastrointestinal systems at 41.8% vs. 36.2%, p < 0.0001, and the classes of drugs implicated in the ADRs are lopinavir-ritonavir 16.3%, antibiotics 24.1%, and hydroxychloroquine12.8%. Furthermore, the duration of hospitalization and polypharmacy are significantly higher in patients with ADRs at 14.13 ± 7.87 versus 9.55 ± 7.90, p < 0.001, and 9.74 ± 5.51 versus 6.98 ± 4.36, p < 0.0001, respectively. Comorbidities are detected in 42.5% of patients and 75.2%, of patients with DM, and HTN, displaying significant ADRs, p-value < 0.05. This is a symbolic study providing a comprehensive acquaintance of the importance of APIs in detecting hospitalized ADRs, revealing increased detection rates and robust assertive values with insignificant costs, incorporating the hospital EMR database, and enhancing transparency and time effectiveness.

A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes.

Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.

Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies.

INTRODUCTION: Vancomycin administration in individuals with hematological malignancy or neutropenia is associated with a suboptimal trough concentration. Nonetheless, most studies did not distinguish whether low vancomycin trough concentrations were due to hematological malignancies or neutropenia. This study aimed to determine the association between types of hematological malignancy and febrile neutropenia with low vancomycin concentrations. METHODS: The present retrospective chart review study was conducted by using clinical data adopted from computerized physician order entries (BestCare®) for all of the patients who received intravenous vancomycin treatment between January 2017 and December 2020 at King Abdulaziz Medical City in Jeddah. RESULTS: Out of the 296 patients, 217 were included. There was no significant association between the type of hematological malignancy and the incidence of a low trough concentration (p > 0.05), while a significant association between febrile neutropenia and the incidence of a low trough concentration was observed (p < 0.05). Furthermore, the predictors for a low trough among febrile neutropenic patients were creatinine clearance (CrCI) and a low albumin concentration. In addition, there was a significant association between febrile neutropenia and augmented renal clearance (p < 0.05). CONCLUSIONS: The findings of this study conclude that febrile neutropenia is associated with low vancomycin concentrations. Interestingly, augmented renal clearance was observed in most of the febrile neutropenia patients with a significant association, which is considered the main driver for a low trough in neutropenic patients.

Effect of Vitamin K on Bone Mineral Density and Fracture Risk in Adults: Systematic Review and Meta-Analysis.

Recent studies have proposed that adequate intake of Vitamin K (VK) is associated with a low risk of fracture and high bone mineral density (BMD) to improve skeletal health in adults. This systematic review was designed to summarize the most relevant and updated evidence discussing the relationship between VK and bone. It explores the effect of VK deficiency and its supplementation on various bone parameters. Methods: The distinct databases such as PubMed, the Cochrane Library, Google Scholar, National Clinical Trials, Current Controlled Trials, and Clinical Trials were searched up to Jan 2020 to identify eligible trials. All relevant randomized controlled trial studies with any oral dosage form of VK supplement administered for at least six months and assessing BMD or fracture in adults were extracted. Finally, two independent reviewers identified 20 relevant citations for the systematic review and extracted data in tabular form. Results: The meta-analysis was performed with all studies, including postmenopausal and osteoporotic females, for both total clinical and vertebral fracture outcomes. The quantitative analysis showed that the odds ratios (OR) of any fracture were lower for VK as compared to control [OR 0.42 (95% CI 0.27 to 0.66)] for vertebral fractures and OR of 0.44 (95% CI 0.23 to 0.88) for clinical fracture. For the BMD, a meta-analysis of the pooled effect of interventional studies suggested a non-significant association between the use of VK and improvement in femoral BMD (CI 95%, p = 0.08 [-0.03-0.20]). Conclusion: VK decreases general fracture risk, and it can be an option to counter bone loss disorders. However, insufficient evidence is available regarding the significant impact of VK on femoral neck BMD. Therefore, further studies are required to establish the therapeutic value of VK as a treatment for osteoporosis.

Pharmacological basis for the potential role of Azithromycin and Doxycycline in management of COVID-19.

A novel corona virus SARS-CoV-2 has led to an outbreak of the highly infectious pandemic COVID-19 complicated viral pneumonia. Patients with risk factors frequently develop secondary infections where the role of appropriate antibiotics is mandatory. However, the efforts of drug repurposing lead to recognizing the role of certain antibiotics beyond the management of infection. The current review provided the detailed antiviral, immunomodulatory effect, unique pharmacokinetic profile of two antibiotics namely azithromycin (AZ) and doxycycline (DOX). It summarizes current clinical trials and concerns regarding safety issues of these drugs. Azithromycin (AZ) has amazing lung tissue access, wide range antibacterial efficacy, conceivable antiviral action against COVID-19. It also showed efficacy when combined with other antiviral drugs in limited clinical trials, but many clinicians raise concerns regarding cardiovascular risk in susceptible patients. DOX has a considerable role in the management of pneumonia, it has some advantages including cardiac safety, very good access to lung tissue, potential antiviral, and immunomodulation impact by several mechanisms. The pharmacological profiles of both drugs are heightening considering these medications for further studies in the management of COVID-19.

Effects of Methanolic Extract Based-Gel From Saudi Pomegranate Peels With Enhanced Healing Potential on Excision Wounds in Diabetic Rats.

Introduction: Current study was designed to evaluate the wound healing activity of a Saudi pomegranate peel extract on excision wound healing in experimentally induced diabetes in rats. Methodology: Animals were divided into three groups: diabetic excision wound with no treatment, diabetic excision wound with gel alone and diabetic excision wound with Saudi pomegranate peel extract in gel. Animals were monitored for clinical signs, weekly body weight, morbidity and mortality during entire study period. The efficacy parameters evaluated were percent wound contraction, Hydroxyproline content, estimation of Transforming Growth Factor ß1 (TGF-ß1), Vascular Endothelial Growth Factor (VEGF), and Epidermal Growth Factor (EGF) in wound lysates by ELISA, mRNA expression of TGF-ß1, VEGF, and EGF in wound lysates by qPCR, Estimation of nitric oxide (NO) and NO synthase (NOS) in Wound Lysates and histopathology of skin for reepithelization, neovascularization, and inflammation. Results: The Saudi pomegranate peel extract in gel (5.0 g extract per 100 g gel) showed significant wound healing activity when compared to the vehicle control [p < 0.05] following 21 days of treatment. Animals in the control and treatment groups were apparently normal through the study with no significant differences in body weights between groups. Expression of mRNA of TGFß1, EGF and VEGF in wounds was the highest on day 14 post treatment 4.3, 3.5 and 0.9 fold higher respectively in the treatment group when compared to vehicle control, and on day 21, the values were 0.12, 0.3 and 0.83, respectively. No statistically significant differences were observed in TGF-ß1 levels in wounds on days 4, 7, 14 and 21 post treatment when compared to the vehicle control (p > 0.05). Significantly higher levels of VEGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Significantly higher levels of EGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Mean hydroxyproline levels were higher in treatment group on days 4 and 7 when compared to vehicle control. NO levels in treatment group were significantly lower on days 7, 14 and 21 when compared to vehicle control (p < 0.05). NOS activity in treatment group were significantly lower on days 4 and 7 when compared to vehicle control (p < 0.05). Histopathological changes in skin wound in the treatment group were consistent with wound healing when compared to the vehicle group. Conclusion: This study's findings suggest that topical application of SPPE gel effectively enhanced wound healing in experimentally induced diabetic conditions.

Tetramethylpyrazine ameliorates indomethacin-induced gastric ulcer in rats: Impact on oxidative, inflammatory, and angiogenic machineries.

Available antiulcer medications reveal partial efficacy and numerous adverse reactions. Tetramethylpyrazine (TMP) was known for its potential antioxidant, anti-inflammatory and angiogenic properties. The aim of current study was to investigate the potential gastroprotective effect of TMP against indomethacin-induced gastric ulcer in rats with possible underlying mechanisms. TMP was tested at 3 doses (15, 30 & 60 mg/kg/d po) three days before indomethacin challenge (25 mg/kg ip). Gastric tissue was evaluated morphologically and histopathologically. Oxidative statuses were assessed via glutathione content (GSH), malondialdhyde (MDA) and catalase (CAT) activity, while TNFα and IL-6 were measured as inflammatory mediators. Gastric PGE2 was investigated in addition to vascular endothelial growth factor (VEGF). TMP was effective (at 30 and 60 mg/kg/d) in promoting mucus secretion and preventing histopathologic changes induced by indomethacin. Mechanistically, TMP significantly enhanced GSH content and CAT activity while reducing lipid peroxidation as expressed by MDA concentration. Moreover, TMP effectively reduced TNFα, IL-6 and intracellular adhesion molecule (ICAM-1) concentrations. On the other hand, TMP enhanced both COX-1 and PGE2 and encouraged angiogenesis via increasing VEGF expression. In conclusion, TMP possesses a protective effect against indomethacin-induced gastric ulcer. This could be explained - at least partly - by its antioxidant, anti-inflammatory and angiogenic effects.

Incorporating ifosfamide into salvia oil-based nanoemulsion diminishes its nephrotoxicity in mice inoculated with tumor.

Introduction: Nephrotoxicity is one of the major side effects of the chemotherapeutic drug, ifosfamide (IFO). In this study, IFO was solubilized in nanoemulsion (NE) containing salvia (SAL) essential oil to investigate its adverse side effects in mice. Methods: One hundred female Swiss albino mice (n = 20/group) were split into five groups. Group I (Normal) received saline solution (0.9% (w/v) NaCl) while groups II-V were intraperitoneally (I.P.) injected with 2.5 × 106 Ehrlich ascetic carcinoma (EAC) cells/mouse. Group II (EAC) represented the untreated EAC-bearing mice. Group III (IFO) was treated with IFO at a dose of 60 mg/kg/d (I.P. 0.3 mL/mouse). Group IV (SAL) was treated with 0.3 mL blank NE-based SAL oil/mouse. Group V (SAL-IFO) was treated with IFO, loaded in 0.3 mL of blank SAL-NE, at a dose of 60 mg/kg/d (I.P. 0.3 mL/mouse). Groups III-V were treated for three consecutive days. Results: There was a double increase in the survival percentage of the SAL-IFO group (60%) relative to the IFO group (30%). Renal damage with the presence of Fanconi syndrome was indicated in the IFO group through a significant elevation in the levels of serum creatinine, blood urea nitrogen, urine bicarbonate, and phosphate in addition to a reduced level of glucose compared to the normal group. On the other hand, the administration of SAL-IFO into the mice reversed this effect. Additionally, the oxidative stress in the kidney tissues of the SAL-IFO group was ameliorated when compared to the IFO group. Conclusion: Incorporating IFO into SAL-NE has protected the kidneys from the damage induced by IFO.

Modulation of doxorubicin-induced expression of the multidrug resistance gene in breast cancer cells by diltiazem and protection against cardiotoxicity in experimental animals.

BACKGROUND: Doxorubicin (DOX) is one of the most important anticancer agents used in treating breast cancer. However, chronic cardiotoxicity and multidrug resistance limit the chemotherapeutic use of DOX. METHODS: This study aimed to evaluate the capability of calcium channel blocker diltiazem (DIL) to reverse DOX resistance in breast cancer MCF-7 cells and to confer protection against DOX-induced cardiotoxicity in Wistar rats. For this purpose, we explored the effects of DOX on cell cycle phase distribution and expression of ABCB1, FOXO3a, and p53 genes in the presence and absence of DIL (20 µg/ml) and studied the ability of DIL to prevent DOX-induced cardiotoxicity after a single injection of DOX (15 mg/kg) in male Wister rats. RESULTS: We found that compared with DOX alone treatment, DIL + DOX treatment down regulated the ABCB1 gene expression by > fourfold but up regulated the FOXO3a and p53 genes expression by 1.5 fold. DIL treatment conferred protection against DOX-induced cardiotoxicity, as indicated by a decrease in the levels of the cardiac enzyme creatine kinase MB and malondialdehyde and an increase in the total antioxidant capacity and glutathione peroxidase levels. These biochemical results were further confirmed by the histopathological investigation of cardiac cells, which showed normal cardiac cells with central vesicular nuclei and prevention of DOX-induced disruption of normal cardiac architecture in the DIL to DOX group. CONCLUSIONS: Taken together, our results indicate that DIL treatment can reverse the resistance of breast cancer cells to the therapeutic effects of DOX and can protect against DOX-induced cardiotoxicity in rats.

Incorporation of ifosfamide into various essential oils -based nanoemulsions ameliorates its apoptotic effect in the cancers cells.

The chemotherapeutic drugs, loaded in nanocarriers, have recently attracted the pharmaceutical industries due to their limited adverse side effects. The objective of the current study was to incorporate the ifosfamide (IFO) into two different essential oils-based nanoemulsions, lemon (LEM-IFO) and salvia (SAL-IFO). The antiproliferation activities of the resulted formulas were evaluated in the MCF-7 breast cancer cells and HeLa cervical cancers cells. The cytotoxic effect of the NE formulas was detected by the MTT assay, DAPI stain and light microscopy. The z-average diameters range of LEM-IFO and SAL-IFO, determined by the zetasizer, were 49.15-61.81 nm and 56.64-64.62 nm, respectively. The half maximal inhibitory concentration (IC50) of LEM-IFO and SAL-IFO, applied into the HeLa cells, were 0.165 ± 0.025 and 0.141 ± 0.035 mM, respectively, whereas the IC50 of LEM-IFO and SAL-IFO subjected into the MCF-7 cells were 0.200 ± 0.005 mM and 0.270 ± 0.025 mM, respectively. The IC50 of the free IFO was markedly larger than LEM-IFO and SAL-IFO when applied into MCF-7 cells (9.20 ± 2.01 mM) and HeLa cells (7.69 ± 1.88 mM). Among the tested formulas, LEM-IFO and SAL-IFO have the greatest apoptotic effect on the MCF-7 and HeLa cells, respectively. Solubilizing the IFO in the essential oils-based NE has ameliorated the antitumor efficacy of IFO.

Ursolic acid rich Ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: Pharmacological and docking studies.

BACKGROUND: Ursolic acid (UA) is a promising molecule with anti-inflammatory, analgesic and potential anti-arthritic activity. METHODS: This study was undertaken to make formulation and evaluation of Ocimum sanctum L. leaf extract (OLE) loaded nano-structured lipid carriers (OLE-NLCs) for improved transdermal delivery of UA. Different surfactants, solid lipids and liquid lipids were used for the preparation of NLCs. The NLCs were developed using emulsion solvent diffusion and evaporation method. Different physicochemical properties, entrapment efficacy, in vitro release evaluation, and ex vivo permeation studies of the prepared NLCs were carried out. The in vivo anti-arthritic activity of OLE-loaded NLC gel and control gel formulation (OLE free NLC gel) against Complete Freund's Adjuvant (CFA) induced arthritis in wister albino rats was also carried out. RESULTS: OLE-NLCs were composed of spherical particles having a mean particle size of ~120 nm, polydispersity index of ~0.162 and zeta potential of ~ -27 mV. The high entrapment efficiency (EE) of UA ~89.56% was attained. The in vitro release study demonstrated a prolonged release of UA from the NLCs up to 12 h. The developed formulation was found to be significantly better with respect to the drug permeation amount with an enhancement ratio of 2.69 as compared with marketed formulation. The in vivo biological activity investigations, studies showed that the newly prepared NLCs formulation of OLE showed excellent anti-arthritic activity and the results were found at par with standard marketed diclofenac gel for its analgesic and anti-arthritic activities. These results were also supported by radiological analysis and molecular docking studies. CONCLUSION: The overall results proved that the prepared OLE-NLCs were very effective for the treatment of arthritis and the results were found at par with standard marketed the standard formulation of diclofenac gel.

Characterization of the Antinociceptive Mechanisms of Khat Extract (Catha edulis) in Mice.

This study investigated the antinociceptive mechanisms of khat extract (100, 200, and 400 mg/kg, i.p.) in four pain models: two thermic (hot plate, tail-flick) and two chemical (acetic acid, formalin) models. Male mice were pretreated intraperitoneally (i.p.) with the opioid receptor blocker naloxone (5 mg/kg), the cholinergic antagonist atropine (2 mg/kg), the selective α1 blocker prazosin (1 mg/kg), the dopamine D2 antagonist haloperidol (1.5 mg/kg), or the GABAA receptor antagonist, bicuculline (1 mg/kg) 15 minutes prior to i.p. injection of khat extract (400 mg/kg). Khat extract reduced the nociceptive response of mice in the four pain tests. Naloxone significantly inhibited the antinociceptive effect of khat extract in the hot plate, tail-flick, and the first phase of formalin tests. Bicuculline significantly antagonized the antinociceptive effect of khat extract on the hot plate and tail-flick tests. Haloperidol significantly reversed the antinociceptive effect of khat extract on the tail-flick test and the first phase of formalin test. These results provide strong evidence that the antinociceptive activity of khat extract is mediated via opioidergic, GABAergic, and dopaminergic pathways. The mechanism of the antinociceptive action of khat may be linked to the different types of pain generated in animal models.

Detection of adverse drug reactions by medication antidote signals and comparison of their sensitivity with common methods of ADR detection.

OBJECTIVE: To determine the PPVs of selected ten medication antidote signals in recognizing potential ADRs and comparison of their sensitivity with manual chart analysis, and voluntary reporting recognizing the same ADRs. METHOD: The inpatient EMR database of internal medicine department was utilized for a period of one year, adult patients prescribed at least one of the ten signals, were included in the study, recipient patients of antidote signals were assessed for the occurrence of an ADR by Naranjo's tool of ADR evaluation. PPVs of each antidote signal were verified. RESULT: PPV of Methylprednisolone and Phytonadione was 0.28, Metoclopramide and Potassium Chloride - 0.29, Dextrose 50%, Promethazine, Sodium Polystyrene and Loperamide - 0.30, Protamine and Acetylcysteine - 0.33. In comparison of confirmed ADRs of antidote signals with other methods, Dextrose 50%, Metoclopramide, Sodium Polystyrene, Potassium Chloride, Methylprednisolone and Promethazine seem to be extremely significant (P value > 0.0001), while ADRs of Phytonadione, Protamine, Acetylcysteine and Loperamide were insignificant. CONCLUSION: Antidote medication signals have definitive discerning evaluation value of ADRs over routine methods of ADR detection with a high detection rate with a minimum cost; Their integration with hospital EMR database and routine patient safety surveillance enhances transparency, time-saving and facilitates ADR detection.

Antihyperglycemic Potential of Grewia asiatica Fruit Extract against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms.

Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200 mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1ß, and tumor necrosis factor- (TNF-) α are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1ß and TNF-α. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic ß-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect.

Phytochemical screening and protective effects of Trifolium alexandrinum (L.) against free radical-induced stress in rats.

Trifolium alexandrinum is traditionally used in various human ailments, including renal dysfunctions. The present experiment was designed to investigate antioxidant and nephroprotective effect of T. alexandrinum methanolic extract (TAME) against CCl4-induced oxidative stress in albino rats. Results of in vitro study revealed significant (P < 0.05) antioxidant effects. The ameliorative role of TAME was also examined by investigating the level of antioxidant enzymes catalase (CAT), peroxidase (POD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), nonenzymatic antioxidant viz; reduced glutathione contents (GSH) and lipid peroxidation products (TBARS) in the renal tissue homogenate in CCl4-treated rats. The intraperitoneal injection of 1 mL/kg b.w. CCl4 caused a significant depletion in the activity antioxidant enzymes and increased the TBARS contents. Supplementation of TAME at 200 mg/kg b.w. for 2 weeks significantly improved activities of antioxidant enzymes and reduced TBARS formation. Co-treatment of TAME also presented significant protection in maintaining renal urine and serum markers. Antioxidant and nephroprotective effects of TAME are associated with its polyphenolic constituents.

Appraisal of antimicrobial prescribing practices of governmental and non-governmental dentists for hospitals in the western region of Saudi Arabia.

OBJECTIVE: To scrutinize the knowledge, attitude, and antimicrobial practices in Saudi Arabian Dentistry. METHODS: In this cross-sectional survey of dentists, a self-administered questionnaire comprising of 61 questions was dispersed to the participants randomly, which included their professional profile, awareness of the current scope of antimicrobial resistance, prescribing practice, frequency of antimicrobial prescription, and sources of continuing education of antimicrobials. The study took place in the Faculty of Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between February and April 2013. RESULTS: Knowledge and awareness concerning specific antimicrobials, with specific oral cavity lesion was 78% for the students and interns, 80% for residents, and 95.3% for specialists. Approximately 89% of the students, interns and residents, and 98.4% of the specialists endorsed indiscriminate use of antibiotics. In addition, 93.4% of students, 90% of interns and residents, and 90.6% of specialists agreed that lack of health education is one of the contributors to overuse of antimicrobials. Moreover, 91.9% of the interns, 80% of residents, and 75.5% of specialists preferred amoxicillin + clavulanate as their first choice; however, a wide variation in the dosage frequency, and duration was observed. CONCLUSION: Participants are well aware of the significance of antimicrobial resistance, and considered that judicious use of antimicrobials is highly imperative to restrain this fiery predicament. Divergence was demonstrated between specialists and residents in prescribing practices. Institutional antimicrobial guideline was not interesting to all the respondents. This highlights the need for incessant instructive intervention in order to accomplish the prime objective of retreating antimicrobial resistance.

Mechanisms of cardioprotective effect of aged garlic extract against Doxorubicin-induced cardiotoxicity.

Aged garlic has been extensively studied and has been shown to have a number of medicinal properties, including immunomodulatory, hepatoprotective, antimutagenic, anticarcinogenic, and antioxidant effects. The objective of this study was to investigate the mechanisms of the cardioprotective effect of aged garlic extract (AGE), a widely used herbal medicine with potent antioxidant activity, against doxorubicin-induced cardiotoxicity. Moreover, the study investigated if the cardioprotective effect of AGE might be at the expense of the antitumor effect of the anticancer drug doxorubicin (DOX). Primary cultured neonatal rat cardiac myocytes were treated with DOX, AGE, and their combination for 24 hours. DOX increased p53 and caspase 3 activity-induced apoptotic cell death, whereas AGE pretreatment suppressed the action of DOX. AGE pretreatment did not interfere with the cytotoxic activity of DOX, but it increased the DOX uptake into tumor cells and increased the long term survivors of tumor-bearing mice from 30% to 70%. In conclusion, DOX impairs viability of cardiac myocytes, at least partially by activating the p53-mediated apoptotic signaling. AGE can effectively and extensively counteract this action of DOX and may potentially protect the heart from severe toxicity of DOX. At the same time, AGE did not interfere with antitumor activity of DOX.