Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Pharmacological and metabolomic profiles of Musa acuminata wastes as a new potential source of anti-ulcerative colitis agents.

Musa acuminata (MA) is a popular fruit peels in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic approaches were found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS2 fragmentation and NMR spectroscopy. These include: cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside; gallic acid and flavonoids; quercetin, quercetin-3-O-ß-D-glucoside, luteolin-7-O-ß-D-glucopyranoside. GC/MS analysis of MA peels essential oil led to identification of 37 compounds. The leaves, pseudostem and fruit peels extracts were tested for their safety and their anti-ulcerative colitis efficacy in rats. Rats were classified into: normal, positive, prednisolone reference group, MA extracts pretreated groups (250-500 mg/kg) for 2 weeks followed by induction of ulcerative colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examinations were done. Inflammatory markers (ANCA, CRP and Ilß6) were measured in sera. The butanol extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of ulcerative colitis and lowered the inflammatory markers compared to untreated group. MA wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-ulcerative colitis food supplements.

Iron supplementation ameliorates aloin-induced iron deficiency anemia in rats.

Aloin, an anthraquinone glycoside, is one of other C-glycosides found in the leaf exudate of Aloe plant. Aloin possesses several biologic activities, including antitumor activity in vitro and in vivo. However, aloin treatment has shown iron deficiency anemia and erythropoiesis in vivo. The present study was undertaken to verify if iron supplementation could alleviate these perturbations, compared to doxorubicin, an anthracycline analog. Oral iron supplementation (20.56 mg elemental Fe/kg bw) to aloin-treated rats normalized red blood corpuscles count, hemoglobin concentration, and serum levels of total iron binding capacity and saturated transferrin, as well as hepatic iron content, hepcidin level, and mRNA expression of ferritin heavy chain (Ferr-H) and transferrin receptor-1 (TfR-1) genes. Although, serum hyperferremia, and leukocytosis were maintained, yet the spleen iron overload was substantially modulated. However, combined aloin and iron treatment increased iron storage levels in the heart and bone marrow, compared to aloin treatment per se. On other hand, oral iron supplementation to rats treated with doxorubicin (15 mg/kg bw) lessened the increase in the spleen iron content concomitantly with hepatic hepcidin level, rebound hepatic iron content to normal level, and by contrast augmented serum levels of iron and transferrin saturation. Also, activated Ferr-H mRNA expression and repressed TfR-1 mRNA expression were recorded, compared to doxorubicin treatment per se. Histopathological examination of the major body iron stores in rats supplemented with iron along with aloin or doxorubicin showed an increase in extramedullary hematopoiesis. In conclusion, iron supplementation restores the disturbances in iron homeostasis and erythropoiesis induced by aloin treatment.

Estrogenic activity of Sage (Salvia officinalis L.) aerial parts and its isolated ferulic acid in immature ovariectomized female rats.

ETNOPHARMACOLOGICAL RELEVANCE: Common sage (Salvia officinalis L., Lamiaceae), a medicinal plant of Mediterranean origin, has been traditionally applied in cases of excessive sweating, and in menopausal complaints, including hot flushes. AIM OF THE STUDY: This study aims to study the possible estrogenic effect of the aerial parts of S. officinalis ethanolic extract in immature ovariectomized female rats. MATERIALS AND METHODS: The ethanolic extract was subjected to qualitative and quantitative HPLC analysis and phytochemical isolation. The estrogenic activity of S. officinalis ethanolic extract at oral doses of 50, 100 and 200 mg/kg b.wt. and its isolated ferulic acid at a dose of 50 mg/kg b.wt. for a week, was assessed on ovariectomized immature Wistar rats. The experiment was confirmed by luteinizing hormone (LH) and follicle stimulating hormone (FSH) serum levels determination, a histopathological examination and a histomorphometrical study. RESULTS: HPLC/PDA analysis revealed fourteen phenolic compounds the major constituents were methyl rosmarinate (24.86 mg/100 g) and ferulic acid (6.06 mg/100 g) together with five flavonoids where the major constituents were rutin, naringenin and quercetin. Two compounds were isolated from the polar fraction and identified as methyl rosmarinate (1) and ferulic acid (2). Oral administration of sage ethanolic extract and ferulic acid revealed a significant increase in the uterine weight compared to ovariectomized control rats. Moreover, S. officinalis and ferulic acid showed different phases of estrus cycle denoting estrogenic activity, and significantly decreased the serum levels of FSH and LH. CONCLUSION: From these results it could be concluded that S. officinalis ethanolic extract and its content of ferulic acid could be useful as a safe natural source for estrogenic activity, supporting its traditional use to improve postmenopausal symptoms.

Neuropathological and Cognitive Effects Induced by CuO-NPs in Rats and Trials for Prevention Using Pomegranate Juice.

Copper oxide nanoparticles (CuO-NPs) are extensively utilized in several industries and in pharmaceutical production. This excess exposure elevates the concern about its expected poisonous impacts on humans and animals. Pomegranate juice (PJ) is a natural source of polyphenols and exhibits potent antioxidant activities. Our experiment intended to explore the neurobehavioral and toxicopathological impacts of CuO-NPs and to explain the mechanistic role of PJ to reduce their toxicity. Thirty Wistar albino rats received the subsequent materials through oral gavage, every day for 28d: (1) normal saline, (2) 3 mL/kg bwt PJ, (3) 6 mL/kg bwt PJ, (4) 300 mg/kg bwt CuO-NPs, (5) CuO-NPs + 3 mL/kg bwt PJ, (6) CuO-NPs + 6 mL/kg bwt PJ. Continuous exposure to CuO-NPs caused a significant elevation of MDA levels and reduction of total antioxidant capacity associated with remarkable pathological alterations in all brain regions including cerebrum, hippocampus and cerebellum. Progressive decline of memory along with cognitive and psychiatric disturbances were observed in rats exposed to CuO-NPs not in PJ co-treated rats. Continuous exposure to CuO-NPs caused over expression of the immunohistochemical markers of caspase-3, iNOS and GFAP altogether with DAN fragmentation and down-regulation of HO-1 and Nrf2 gene in the whole brain tissues. Conversely, rats co-treated with PJ showed dose dependent improvements in the entire toxicological, behavioral, and pathological parameters. We showed that PJ had the ability to reduce the oxidative stress damage via up-regulation of HO-1 and Nrf2 genes in the brain. So that PJ had the ability to protect the brain and DNA from further damage.

Therapeutic potential of russelioside B as anti-arthritic agent in Freund's adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Caralluma species are traditional edible herbs used in folkloric medicine as antidiabetic, antioxidant, antipyretic, antirheumatic, anti-inflammatory and anthelmintic agents. C. quadrangula was selected in this study to document the traditional use of the genus as anti-rheumatic treatment and the possible mechanisms of action. AIM OF THE STUDY: The higher mortality rates and shorter survival among the patients suffering from rheumatoid arthritis (RA) led to the increased interest on searching for new treatments for RA. Russelioside B (RB), a major pregnane glycoside found in C. quadrangula, was evaluated as a new anti-rheumatic agent. MATERIALS AND METHODS: The n-butanol fraction of C. quadrangula was chromatographed on a silica gel column to isolate RB. The adjuvant-induced arthritis (AIA) model was established in rats by intradermal injection of complete Freund's adjuvant (CFA) to evaluate its anti-arthritic effect. Ibuprofen was used as a reference drug. Forty rats were randomly divided into 5 groups (n = 8): normal (NOR); CFA model (CFA); ibuprofen, 5 mg/kg; RB, 25 mg/kg and RB, 50 mg/kg. The treatments were initiated from day 16 when AIA model was established and continued up to day 40. Serum diagnostic rheumatoid markers, inflammatory cytokines, oxidative stress biomarkers, cartilage and bone degeneration enzymes were assessed. RESULTS: RB at 50 mg/kg b. wt., showed significant decreases in the activities of hyaluronidase and ß-glucouronidase enzymes as well significant decreases in the levels of proinflammatory cytokines as nuclear factor-kappa-B (NF-κB), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) compared to the CFA group; 11.04 ± 0.61 pg/mg protein, 4.35 ± 0.25 pg/mg protein, 3.32 ± 0.13 pg/mg protein & 2.75 ± 0.14 pg/mg protein for RB, 50 mg/kg b. wt. group vs. 25.33 ± 2.13 pg/mg protein, 25.65 ± 2.1 pg/mg protein, 22.20 ± 1.34 pg/mg protein & 13.27 ± 1.40 pg/mg protein for the arthritic group, respectively. The total antioxidant capacity (TAC) was significantly restored to normal values in RB, 50 mg/kg treated rats (4.01 ± 0.09 nmol/mL vs. 3.71 ± 0.27 nmol/mL) and the levels of myeloperoxidase (MPO) reduced by 10-folds of the CFA arthritic group. Bone histomorphometry revealed that RB treatment significantly attenuated the CFA-induced bone loss in a dose-dependent manner. CONCLUSIONS: These findings suggested that the anti-arthritic effect of RB was mediated through the reduction of the rheumatoid markers, anti-inflammatory and antioxidant action, inhibition of cartilage and bone degenerative enzymes as well as attenuation of bone loss and osteoclastogenesis.

A mechanistic study of Solenostemma argel as anti-rheumatic agent in relation to its metabolite profile using UPLC/HRMS.

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel (Argel) is a traditional perennial edible herb that is commonly used in folkloric medicine for the treatment of rheumatic pain, inflammation, bronchitis, cold, diabetes, gastrointestinal cramps, and urinary tract infections. No previous reports traced the mechanistic activity of this plant for treatment of rheumatoid arthritis in relation to its chemical constituents. AIM OF THE STUDY: The present study was designed to substantiate the anti-arthritic potential of S. argel and identification of its secondary metabolites responsible for the action using ultra-performance liquid chromatography coupled to high resolution mass spectrometry (UPLC/HRMS). MATERIALS AND METHODS: The air-dried powder of S. argel was subjected to liquid-liquid fractionation method to yield polar metabolites fraction (PMF) and nonpolar metabolites fraction (NPMF) where the metabolites that represent each fraction were identified using UPLC/HRMS. The in-vitro anti-arthritic effects of both fractions were tested using protein denaturation, membrane stabilization and proteinase inhibition assays, in addition to in-vitro enzyme inhibition assays of COXs, LOX and collagenases. Adjuvant-induced arthritis (AIA) model was also established to evaluate their anti-arthritic effects in-vivo at two doses (200 and 400 mg/kg) in compared to the standard ibuprofen (5 mg/kg). Physical changes with hind paw edema and body weight gain as well as the assessment of serum rheumatoid biomarkers, inflammatory cytokines, oxidative stress markers, and the activity of hyaluronidase and ß-glucouronidase enzymes were studied. The histopathological study of ankle and knee joints and immunohistochemistry of caspase-3 and TNF-α in joint synovium were also examined. RESULTS: The PMF significantly (P < 0.05) reduced paw edema, serum rheumatoid markers, pro-inflammatory mediators, degeneration enzymes of cartilage and bone, and oxidative stress biomarkers. Interestingly, flavonoid glycosides and phenolic acids dominated the polar fraction, which showed the promising anti-arthritic activity of Argel compared to the NPMF which was dominated by pregnane glycosides. CONCLUSIONS: Since arthritis is a chronic disease and there are imperative needs for a lifelong treatment with desirable pharmacological action and lower cost than the currently approved synthetic drugs having severe side effects, the PMF of Argel could be used as a potent anti-rheumatic agent.

Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy.

This study examines the protective effects of omega-3 fatty acids (OMG), a frequently used nutritional therapy in cancer patients, against doxorubicin (DOX)-induced acute cardiorenal toxicity in rats, and evaluates the cytotoxic activity of DOX when used with OMG against breast cancer cell line. Five groups of rats were treated for 4 consecutive weeks with vehicle (groups I & II), or OMG (25, 50 or 100 mg/kg/day, po; groups III, IV & V, respectively). After twenty-four hours, the last four groups were injected with DOX (200 mg/kg, ip). In DOX-treated rats, the altered ECG, serum cardiac and renal function biomarkers, and histopathological features indicated the induction of cardiorenal toxicity. Increased oxidative and apoptotic markers in both organs was observed, with elevated renal contents of NADPH-oxidase-4 (Nox4) and renin. OMG pretreatment improved those DOX-induced impairments in a dose-dependent manner, and showed antioxidant and antiapoptotic effects with regulation of renal Nox4 expression. The in-vitro study showed preservation of the cytotoxic activity of DOX on MCF7 cell line in the presence of OMG. The data suggests OMG for protection against acute DOX-induced cardiorenal damage without affecting the latter antitumor activity. It proposes regulation of oxidative stress, Nox4 activity and apoptosis as contributing protective mechanisms.

Ginseng attenuates fipronil-induced hepatorenal toxicity via its antioxidant, anti-apoptotic, and anti-inflammatory activities in rats.

Fipronil (FPN) is a relatively new and broad spectrum insecticide that induces toxic effects to animals and humans through induction of oxidative stress. Ginseng is a medicinal plant that has antioxidant, anti-inflammatory, and anti-apoptotic activities. Thus, the current study was conducted to evaluate the anti-toxic potential of ginseng aqueous extract (GAE) against FPN-induced hepatorenal toxicity in rats. Thirty-two male Wistar albino rats were randomly allocated into four equal groups. Rats of the control group received distilled water. The second group was administrated with GAE at a dose of 200 mg/kg b.w. orally day by day for 6 weeks. The third group was intoxicated with FPN at a dose of 4.85 mg/kg b.w. orally day by day for 6 weeks. The fourth group was administrated with GAE 2 h before FPN intoxication. Intoxication of rats with FPN significantly elevated the activities of serum alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine, as well as increased malondialdehyde level and protein expressions of caspase-3 and cyclooxygenase-2 in hepatic and renal tissues. However, it significantly decreased hepatic and renal GSH content and catalase activity. In addition, it induced histopathological alterations in hepatic and renal tissue architectures. Conversely, concomitant oral administration of GAE ameliorated the FPN-induced biochemical, pathological, and histochemical alterations in both hepatic and renal tissues. This study indicated that ginseng attenuates FPN-induced hepatorenal toxicity, possibly via its antioxidant, anti-apoptotic, and anti-inflammatory properties. Graphical Abstract CAL ABSTRACTPHIRAG.

Ginseng aqueous extract ameliorates lambda-cyhalothrin-acetamiprid insecticide mixture for hepatorenal toxicity in rats: Role of oxidative stress-mediated proinflammatory and proapoptotic protein expressions.

This study was carried out to evaluate the protective effects of Panax ginseng aqueous extract (GAE) against hepatorenal toxicity induced by lambda-cyhalothrin-acetamiprid insecticide mixture in rats. A total of 32 male albino rats were assigned into four groups. Normal control group received distilled water. Insecticide control group intoxicated with the insecticide at a dose of 2.14 mg/kg b.wt orally day after day for 45 days. GAE control group was treated with GAE at a dose 200 mg/kg b.wt orally. GAE experimental group was administered GAE 1 hour before insecticide administration. Intoxication of rats with the insecticide caused a significant increase in serum aspartate aminotransferase and alanine aminotransferase activities and urea and creatinine levels as well as malondialdehyde concentration and proteins expression of caspase-3 and induced nitric oxide synthase in hepatic and renal tissues. However, it decreased the serum levels of total protein and globulin and reduced the glutathione content and catalase activity in hepatic and renal tissues. In addition, insecticide induced histopathological alterations in both hepatic and renal tissues. In contrast, GAE modulated insecticide-induced alterations in liver and kidney functions and structures as it ameliorated the effects of insecticide on the above mentioned parameters. These results indicated that GAE was a potent antioxidant agent that could protect rats against insecticide-induced hepatorenal toxicity.

Pomegranate Juice Diminishes The Mitochondria-Dependent Cell Death And NF-kB Signaling Pathway Induced By Copper Oxide Nanoparticles On Liver And Kidneys Of Rats.

BACKGROUND: Pomegranate (Punica granatum L) has been used since ancient times in the traditional medicine of several cultures, particularly in the Middle East. It is an essential commercial crop full of bioactive compounds with several medical applications. Pomegranate is very popular for its biological effects exerted by phenolic compounds via free radical scavenging abilities. It has revealed high antioxidant and anti-inflammatory activities and is beneficial for the amelioration of liver and kidney diseases. PURPOSE: To elucidate the potential efficacy of pomegranate juice (PJ) against copper oxide nanoparticles (CuO-NPs)-induced apoptosis, inflammation, and oxidative stress damage. STUDY DESIGN: 37 nm sized CuO-NPs were prepared by precipitation method and characterized by using X-ray diffractometer (XRD), Zetasizer nano-and high-resolution transmission electron microscope (HR-TEM). 30 Wistar rats were partitioned into 6 equal groups as follows: Group 1 (negative control), groups 2 & 3 (PJ control groups), group 4 (CuO-NPs group), groups 5 & 6 (CuO-NPs + PJ groups). Methods: Hepato-renal protective effect of PJ was evaluated by measuring levels of serum marker enzymes (ALT, AST,blood urea nitrogen and creatinine). Cu NPs bioaccumulation in liver and kidneys was determined by using atomic absorption spectrophotometer. The oxidative stress markers, Rt-PCR analysis, histopathological and immunohistochemical studies were carried out in the liver and kidneys to support the above parameters. RESULTS: Rats injected with CuO-NPs showed higher levels of the above serum marker enzymes, alteration of oxidant-antioxidant balance together with severe pathological alterations in liver and kidney tissues and overexpression of both caspase-3 and nuclear factor kappa B protein (NF-ĸB) associated with upregulation of Bax gene and downregulation of Bcl2 gene in these organs. PJ ameliorated all of the above toxicological parameters. CONCLUSION: PJ was proved to be a potential hepato-renal protective agent against liver and kidney damage induced by CuO-NPs via its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Ambrosin, a potent NF-κß inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κß. NF-κß is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-κß inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin. Memory impairment was induced in mice by single intraperitoneal injection of LPS (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-κßp65 transcript and protein levels. Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNF-α, IL-1ß, COX-2 and iNOS. BACE1 was inhibited, thereby reducing amyloid plaques (Aß) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion, ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics.

Optimizing cancer pain management in resource-limited settings.

PURPOSE: Adequate cancer pain management (CPM) is challenging in resource-limited settings, where current international guideline recommendations are difficult to implement owing to constraints such as inadequate availability and accessibility of opioids, limited awareness of appropriate opioid use among patients and clinicians, and lack of guidance on how to translate the best evidence into clinical practice. The multinational and multidisciplinary CAncer Pain managEment in Resource-limited settings (CAPER) Working Group proposes a two-step initiative to bridge clinical practice gaps in CPM in resource-limited settings. METHODS: A thorough review of the literature, a steering committee meeting in February 2017, and post-meeting teleconference discussions contributed to the development of this initiative. As a first step, we developed practical evidence-based CPM algorithms to support healthcare providers (HCPs) in tailoring treatment according to availability of and access to resources. The second part of the initiative proposes a framework to support an effective implementation of the CPM algorithms that includes an educational program, a pilot implementation, and an advocacy plan. RESULTS: We developed CPM algorithms for first-line use, breakthrough cancer pain, opioid rotation, and refractory cancer pain based on the National Comprehensive Cancer Network guidelines and expert consensus. Our proposed educational program emphasizes the practical elements and illustrates how HCPs can provide optimal CPM according to evidence-based guidelines despite varied resource limitations. Pilot studies are proposed to demonstrate the effectiveness of the algorithms and the educational program, as well as for providing evidence to support a draft advocacy document, to lobby policymakers to improve availability and accessibility of analgesics in resource-limited settings. CONCLUSIONS: These practical evidence-informed algorithms and the implementation framework represent the first multinational step towards achieving optimal CPM in resource-limited settings.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model.

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1ß (IL-1ß), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds.

Communication and integration: a qualitative analysis of perspectives among Middle Eastern oncology healthcare professionals on the integration of complementary medicine in supportive cancer care.

CONTEXT AND OBJECTIVES: The use of complementary and traditional medicine (CTM ) in Middle Eastern countries is widespread, including among patients with cancer. Perspectives of oncology healthcare professionals (HCPs) in this region regarding the integration of CTM within conventional supportive cancer care were explored. METHODS: An 11-item questionnaire with an open-ended question asking respondents to comment about the integration of CTM within supportive cancer care was sent to Middle Eastern oncology HCPs, using snowball sampling methodology. The narratives provided were examined using thematic analysis. RESULTS: A total of 339 oncology HCPs completed and returned the study tool (80.3 % response rate ), of which 178 from 15 Middle Eastern countries responded to the open-ended question. The majority of respondents are in favor of the integration of CTM within supportive cancer care, though ideas on how this should be implemented varied. Thematic analysis identified multifactorial barriers to integration, which focused on HCPs' perspectives (e.g., a lack of knowledge and training; a skeptical approach to CTM), attitudes of patients and caregivers (e.g., unrealistic expectations regarding the outcomes of CTM treatments) and HCP-patient communication. In order to overcome these barriers, respondents suggested education and training programs for oncology HCPs which would focus on improving patients' quality-of-life-related outcomes. CONCLUSIONS: Middle Eastern oncology HCPs support the integration of CTM within supportive cancer care, while recognizing the need for education and training in this field. A better understanding of CTM would provide the knowledge and skills which would promote a non-judgmental, evidence-based approach, fostering better communication with patients.

Potential risks associated with traditional herbal medicine use in cancer care: A study of Middle Eastern oncology health care professionals.

BACKGROUND: The authors assessed the use of herbal medicine by Middle Eastern patients with cancer, as reported by their oncology health care professionals (HCPs). Herbal products identified by the study HCPs were evaluated for potential negative effects. METHODS: Oncology HCPs from 16 Middle Eastern countries received a 17-item questionnaire asking them to list 5 herbal products in use by their patients with cancer. A literature search (PubMed, Micromedex, AltMedDex, and the Natural Medicine Comprehensive Database) was conducted to identify safety-related concerns associated with the products listed. RESULTS: A total of 339 HCPs completed the study questionnaire (response rate of 80.3%), identifying 44 herbal and 3 nonherbal nutritional supplements. Safety-related concerns were associated with 29 products, including herb-drug interactions with altered pharmacodynamics (15 herbs), direct toxic effects (18 herbs), and increased in vitro response of cancer cells to chemotherapy (7 herbs). CONCLUSIONS: Herbal medicine use, which is prevalent in Middle Eastern countries, has several potentially negative effects that include direct toxic effects, negative interactions with anticancer drugs, and increased chemosensitivity of cancer cells, requiring a reduction in dose-density. Oncology HCPs working in countries in which herbal medicine use is prevalent need to better understand the implications of this practice. The presence of integrative physicians with training in complementary and traditional medicine can help patients and their HCPs reach an informed decision regarding the safety and effective use of these products.

Integration of complementary medicine in supportive cancer care: survey of health-care providers' perspectives from 16 countries in the Middle East.

INTRODUCTION: In this multinational Middle-Eastern study, we assessed health-care providers' (HCPs) perspectives on their patients' use of complementary and traditional medicine (CTM) and identified the leading barriers to CTM integration in supportive cancer care. METHODS: A 17-item questionnaire was developed and administered to HCPs attending palliative medicine workshops conducted across the Middle East by the Middle East Cancer Consortium. RESULTS: 339 HCPs from 16 countries across the Middle East completed the questionnaire (80.3 % response rate). Respondents perceived their patients' reasons for CTM use primarily in the context of cancer cure (63 %) and quality of life (QOL) improvement (57 %). Expectation regarding CTM's role in cancer cure/survival was more pronounced in Turkey, Jordan, the Palestinian Authority, and the Persian Gulf area. In contrast, the expectation that CTM would improve QOL was more emphasized in Israel. A mid-position between the cure/survival and QOL poles was observed in Cyprus, Lebanon, and the North African countries. Leading barriers to CTM integration in supportive cancer care included oncologists' skepticism and a gap between patients' expectations and HCP's objectives. Respondents' leading recommendation to HCPs was to communicate integrative care emphasizing well-being and improved functioning in accordance with their patients' health beliefs. CONCLUSION: CTM integration in supportive cancer care can be facilitated by implementing a platform for Middle Eastern clinical collaborations. HCPs' expectations and experiences with CTM have been positive in the oncology setting. These data need to be corroborated with information of patients' expectations on the provision of CTM over all phases of the oncology treatment.

Taurine is more effective than melatonin on cytochrome P450 2E1 and some oxidative stress markers in streptozotocin-induced diabetic rats.

Melatonin and taurine have alleviative effects in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into nondiabetic, diabetic, diabetic melatonin supplemented and diabetic taurine supplemented groups. At the end of the study, both blood and liver were collected for determination of some oxidative stress parameters, and hepatic cytochrome P450 2E1 (CYP2E1) enzyme activity and gene expression. An increased CYP2E1 activity and expression level with a concomitant significant change in oxidative stress parameters were found in STZ-induced diabetic rats. Taurine or melatonin supplementation to the diabetic rats alleviated these experimental parameters with a more significant effect for taurine than that of melatonin. Suppression of ß-hydroxybutyrate (ß-HB) production by taurine can be one of the mechanisms of a reduction in CYP2E1. Taurine was effective more than melatonin in reducing CYP2E1 activity and expression; therefore antioxidants might prove beneficial in type 1 diabetes associated with manifestations of liver injury.

Chemotherapeutic efficacy of a natural combination in the treatment of mansonic schistosomiasis: an experimental study.

PURPOSE: Combination chemotherapy of schistosomiasis mansoni has been studied previously, with praziquantel being the basis of combination. Artemether and myrrh are compounds of a natural origin that have been investigated experimentally and clinically against schistosomiasis. Artemether is used as an antimalarial drug, and has been used as a chemoprophylactic drug against Schistosoma japonicum in China whereas myrrh extract is manufactured and prescribed as an antischistosomal drug in Egypt. The present study investigated the experimental efficacy of combining artemether and myrrh using three different protocols in mice infected with the Egyptian strain of S. mansoni. METHODS: Experiments were performed on 40 eight-week-old female Swiss albino mice divided into three experimental groups and one control group. Assessment of efficacy was based on a suite of parasitologic and histopathologic parameters. Parasitologic parameters included reductions in total and female worm burdens, reductions in hepatic and intestinal wall tissue egg loads, and alterations in oogram patterns in the experimental groups compared to the infected untreated control. Histopathologic parameters comprised microscopic examination of liver sections stained with hematoxylin and eosin to study the reductions in the mean counts and diameters of hepatic granulomas as well as their healing ratios compared to the control. RESULTS: Reductions of 43.9%-58.2% in total worm burdens and 42.4%-63.7% in female worm burdens were induced. Meanwhile, significant reductions of 63.1%-77.8% in eggs per gram of small intestinal tissue and of 56.5%-66.3% in eggs per gram of liver tissue were also observed. The combination also caused alterations in the oogram pattern as well as amelioration of hepatic lesions as evidenced by increased ratios of healed granulomas in the treated groups compared to the control. CONCLUSION: The experimental efficacy of the artemether-myrrh combination against the Egyptian strain of S. mansoni was evident, but not to an extent that would warrant clinical trials in humans.

Myrrh and trematodoses in Egypt: an overview of safety, efficacy and effectiveness profiles.

Myrrh is an herbal product that has been used since ancient ages for traditional medication and other purposes. The revolution of myrrh as an antiparasitic agent in Egypt began in the 1990s through scientific evidence-based research. The human trematode infections in Egypt were the main focus of research with stories of success and disagreement, at times. The present paper reviewed the antiparasitary activity of myrrh with stress on its possible mode of action, its safety, efficacy and effectiveness on trematode infections in experimental studies and clinical trials in Egypt as well as its molluscicidal effects on the intermediate hosts of trematodes.