Patients With Acute-on-Chronic Liver Failure Have Greater Healthcare Resource Utilization After Liver Transplantation.

BACKGROUND & AIMS: Although liver transplantation (LT) has been demonstrated to provide survival benefit for patients with acute-on-chronic liver failure (ACLF), data are lacking regarding resource utilization for this population after LT. METHODS: We retrospectively reviewed data from 10 centers in North America of patients transplanted between 2018 and 2019. ACLF was identified by using the European Association for the Study of the Liver-Chronic Liver Failure criteria. RESULTS: We studied 318 patients of whom 106 patients (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Healthcare resource utilization after LT was greater among recipients with ACLF compared with patients without ACLF regarding median post-LT length of hospital stay (LOS) (P < .001), length of post-LT dialysis (P < .001), discharge to a rehabilitation center (P < .001), and 30-day readmission rates (P = .042). Multivariable negative binomial regression analysis demonstrated a significantly longer LOS for patients with ACLF-1 (1.9 days; 95% confidence interval [CI], 0.82-7.51), ACLF-2 (6.7 days; 95% CI, 2.5-24.3), and ACLF-3 (19.3 days; 95% CI, 1.2-39.7), compared with recipients without ACLF. Presence of ACLF-3 at LT was also associated with longer length of dialysis after LT (9.7 days; 95% CI, 4.6-48.8) relative to lower grades. Multivariable logistic regression analysis revealed greater likelihood of discharge to a rehabilitation center among recipients with ACLF-1 (odds ratio [OR], 1.79; 95% CI, 1.09-4.54), ACLF-2 (OR, 2.23; 95% CI, 1.12-5.01), and ACLF-3 (OR, 2.23; 95% CI, 1.40-5.73). Development of bacterial infection after LT also predicted LOS (20.9 days; 95% CI, 6.1-38.5) and 30-day readmissions (OR, 1.39; 95% CI, 1.17-2.25). CONCLUSIONS: Patients with ACLF at LT, particularly ACLF-3, have greater post-transplant healthcare resource utilization.

Risk Factors for Posttransplantation Mortality in Recipients With Grade 3 Acute-on-Chronic Liver Failure: Analysis of a North American Consortium.

Although liver transplantation (LT) yields survival benefit for patients with acute-on-chronic liver failure grade 3 (ACLF-3), knowledge gaps remain regarding risk factors for post-LT mortality. We retrospectively reviewed data from 10 centers in the United States and Canada for patients transplanted between 2018 and 2019 and who required care in the intensive care unit prior to LT. ACLF was identified using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. A total of 318 patients were studied, of whom 106 (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Survival probability 1 year after LT was significantly higher in patients without ACLF (94.3%) compared with patients with ACLF (87.3%; P = 0.02), but similar between ACLF-1 (88.5%), ACLF-2 (87.8%), and ACLF-3 (85.7%; P = 0.26). Recipients with ACLF-3 and circulatory failure (n = 29) had similar 1-year post-LT survival (82.3%) compared with patients with ACLF-3 without circulatory failure (89.6%; P = 0.32), including those requiring multiple vasopressors. For patients transplanted with ACLF-3 including respiratory failure (n = 20), there was a trend toward significantly lower post-LT survival (P =  0.07) among those with respiratory failure (74.1%) compared with those without (91.0%). The presence of portal vein thrombosis (PVT) at LT for patients with ACLF-3 (n = 15), however, yielded significantly lower survival (91.9% versus 57.1%; P < 0.001). Multivariable logistic regression analysis revealed that PVT was significantly associated with post-LT mortality within 1 year (odds ratio, 7.3; 95% confidence interval, 1.9-28.3). No correlation was found between survival after LT and the location or extent of PVT, presence of transjugular intrahepatic portosystemic shunt, or anticoagulation. LT in patients with ACLF-3 requiring vasopressors yields excellent 1-year survival. LT should be approached cautiously among candidates with ACLF-3 and PVT.

Alleviation of carbendazim toxicity effect by Moringa oleifera oil and Linum usitatissimum L. oil on testes of male rats: Physiological, histological and in silico study.

Carbendazim (CBZ) is a widely used fungicide that is used to control the unwanted growth of fungi on fruits and vegetables. Sixty male rats were divided into six groups, each having ten. Group one served as control, animals belonging to group two were exposed to CBZ in the measure of 200 mg/kg body weight (BW). In the third and fourth groups, rats were administered 800 mg/kg BW of Moringa oleifera (moringa oil) and Linum usitatissimum L. (flaxseed oil), plus CBZ with the same dose given to group two. Groups five and six were administered with moringa and flaxseed oils respectively for six weeks. A marked decline was seen in oxidative stress markers, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and a rise in malondialdehyde (MDA) level in group two with severe histological disruptions. Moringa oil and flaxseed oil were used to alleviate these changes. In addition, a biocomputational molecular docking analysis of three proteins found in male rats was performed. In relation to CBZ (CID:10584007) the screened proteins namely testis-expressed protein (TX101_RAT), EPPI_RAT, and glutathione peroxidase 5 (GPX5_RAT) were docked, and their docking score were obtained (-5.9 kcal/mol), (-5.8 kcal/mol) and (-5.6 kcal/mol) respectively. By examining these interactions in 2D and 3D structures, a detailed understanding of the unique and specific binding affinity, hydrogen bonds, hydrophobic interactions, ionic bonds, and water bonds were obtained. Structure-based virtual screening (SBVS) molecular docking analysis showed that protein interaction with CBZ causes reproductive complications in protein expression and functions by hampering their normal function and blocking active sites.

Attenuating effect of Ginkgo biloba leaves extract on liver fibrosis induced by thioacetamide in mice.

The purpose of this study is to investigate the effect of Ginkgo biloba leaves extract on experimental liver fibrosis induced by thioacetamide (TAA) in male albino mice. The experimental mice were divided into four groups. The mice of the first group were served as control. The experimental animals of the second group were given 150 mg/kg body weight of TAA by intraperitoneal injection, twice weekly, for 9 weeks. The mice of the third group were exposed to TAA and supplemented with G. biloba leaves extract. The animals of the fourth group were supplemented with G. biloba leaves extract. The levels of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, triglycerides, cholesterol, and low-density lipoprotein cholesterol were statistically increased while the levels of plasma total protein, albumin, glucose, and high-density lipoprotein cholesterol were significantly decreased. The levels of liver superoxide dismutase, glutathione, glycogen and total protein were notably declined, whereas the level of total lipid was increased in mice of the second group. Furthermore, microscopic examination of liver sections from mice treated with TAA showed an abnormal morphology characterized by nodular transformations in liver parenchyma which surrounded by fibrous septa. Administration of G. biloba leaves extract reduced extent and development of fibrous septa, liver cells change, and biochemical alterations in mice exposed to TAA. This study showed that G. biloba leaves extract has a potential activity against TAA-induced liver fibrosis and suggested that the chemical constituents of G. biloba are effective in modulation of oxidative stress induced by TAA.

Hematological and biochemical investigations on the effect of curcumin and Thymoquinone in male mice exposed to Thioacetamide.

Currently, living organisms are increasingly exposed to many toxic chemicals in the environment. These substances pose a threat to human life, other living organisms and ecosystem. In fact, there is an increasing requirement to search for safe therapeutic sources today. Medicinal plants and natural products have become of great importance globally because of their therapeutic potential and medicinal properties, as well as their availability and the absence of harmful side effects for most of them. The present study was designed to explore the potential protective effect of curcumin (CUR) and thymoquinone (TQ) in male rats exposed to thioacetamide (TAA). The experimental mice were divided into eight groups. Group 1 was served as control. Group 2 was exposed to 50 mg/ kg body weight of TAA. Group 3 was exposed to CUR and TAA. Mice of group 4 were treated with TQ and TAA. Mice of group 5 were exposed to CUR plus TQ and TAA. Group 6 was supplemented with CUR. Group 7 was subjected to TQ. Mice of group 8 were treated with CUR and TQ. Hematological and biochemical alterations were evaluated after one month. Significant increases of white blood corpuscles (WBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) values were observed in group 2, while the values of red blood corpuscles (RBC), hemoglobin (Hb(, hematocrit (Hct), glutathione (GSH) and superoxide dismutase (SOD) were statistically decreased. Treatment with CUR, TQ and their combination inhibited the hematological and biochemical alterations induced by TAA toxicity. Moreover, the most protective effect was observed in mice treated with CUR plus TQ. These new results suggested that the protective effect of CUR and TQ attributed to their antioxidant properties.

Arabica coffee and olive oils mitigate malathion-induced nephrotoxicity in rat: In silico, immunohistochemical and biochemical evaluation.

Malathion (MAL) is an organophosphate insecticide that disrupts the body's antioxidant system; it is one of the earliest organophosphate insecticides extensively used as dust, emulsion, and vapor control a wide variety of insect pests under different conditions. This experimentation aims to evaluate the influence of Arabica coffee oil and olive oil on MAL-induced nephrotoxicity in male rat. 6 sets bearing the same number of animals were applied to this experiment. Each set comprised 10 rats. The first set of rats was used as the control group; rats in the second set were exposed to MAL measured at 100 mg/kg body weight for 7 weeks. Animals in the third and fourth set were treated with 400 mg/kg body weight of Arabica coffee oil and olive oil, and 100 mg/kg body weight of MAL. The fifth, together with the sixth set, were fed with a similar proportion of Arabica coffee oil and olive oil as administered to the third set of rats. After the experimental duration, rats of group 2 showed severe biochemical alterations, including significant increases of creatinine, uric acids, and urea nitrogen (BUN), resulting in marked decreases in serum albumin values and total protein (TP). Severe histopathological and immunohistochemical alterations of kidney tissues were observed in exposed MAL-intoxicated rats. Administration of these oils reduced the detected biochemical, histopathological modifications caused by MAL intoxication. Two active ingredients in Arabica coffee oil (oleic acid) and olive oil (hydroxytyrosol) showed good cyclooxygenase-2 (COX 2) interaction. Moreover, oleic acid from coffee oil and olive oil exhibited impressive association with xanthine oxidase (XO). The current finding showed that coffee oil and olive oil could be appraised as possible and a likely deterrence component against nephrotoxicity brought about by MAL.

Predominance of Antioxidants in Some Edible Plant Oils in Ameliorating Oxidative Stress and Testicular Toxicity Induced by Malathion.

Malathion (MAL) is an insecticide that has been linked to reproductive system damage in both humans and animals. In the present investigation, the antitoxic effects of coffee and olive oils on MAL-induced testicular dysfunctions were evaluated. MAL-intoxicated rats were supplemented with coffee and olive oils (400 mg/kg) for 7 weeks. Exposure to MAL resulted in statistically altered antioxidant enzymes and histopathological findings of necrotic seminiferous tubules and spermatogenetic arrest in rats after seven weeks of treatment. The effects of MAL intoxication on physiological and histopathological changes were improved by the use of these oils. Murine double minute 2 (MDM2) was found to interact well with chlorogenic acid and oleuropein, two compounds from coffee and olive oils, respectively. Coffee oil and olive oil were found to be promising therapeutic agents for MAL-induced testicular toxicity and oxidative damage.

Therapeutic effects of olive leaves extract on rats treated with a sublethal concentration of carbendazim.

OBJECTIVES: The present study was carried out to establish the possible protective effects of administration of olive leaves extract on carbendazim induced physiological and histopathological alterations in male rats. MATERIALS AND METHODS: The experimental rats were divided randomly into five groups and kept at ten rats per group. The first group was untreated and served as a control. The second group was orally administered with carbendazim (200 mg/kg) for one month. The third group was supplemented with olive leaves extract and exposed to carbendazim at the same dose given to the second group. Rats of the fourth group were supplemented with olive leaves extract at the same dose given to the third group. Rats of the fifth group were supplemented with only corn oil. RESULTS: Carbendazim induced statistically declines in the values of red blood corpuscles (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct) and the level of plasma and liver total protein, while the value of white blood cells (WBC) count, the levels of plasma glucose, triglycerides, cholesterol, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver glycogen and total lipid were elevated. Moreover, after one month of carbendazim exposure, there were severe changes in the structures of liver, kidney and testis. Pretreatment of carbendazim-exposed rats with olive leaves extract showed marked improvement in both physiological and histopathological alterations. CONCLUSIONS: We conclude that olive leaves extract is a promising chemotherapeutic agent for reducing the toxicity of carbendazim and may be for other pesticides and toxicants.

Alleviation of Malathion Toxicity Effect by Coffea arabica L. Oil and Olea europaea L. Oil on Lipid Profile: Physiological and In Silico Study.

The community health plans commonly use malathion (MAL), an organophosphate pesticide (OP), to eliminate pathogenic insects. The objective of the present research is to evaluate the consequences of Coffea arabica L. oil and Olea europaea L. oil on MAL-intoxicated male rats. Six equal groups of animals were used for conducting this study (n = 10). Animals in group one were designated as control, animals belonging to group two were exposed to MAL in the measure of hundred mg per kg BW (body weight) for forty-nine days (seven weeks), rats in the third and fourth groups were administered with 400 mg/kg BW of Coffea arabica L. and Olea europaea L. oils, respectively, and the same amount of MAL as given to the second group. Groups five and six were administered with the same amount of Coffea arabica L. oil and Olea europaea L. oil as given to group three. Exposure of rats to 100 mg/kg body weight of MAL resulted in statistical alteration of the serum lipid profile. A marked decline was noticed in the severe changes of these blood parameters when MAL-intoxicated rats were treated with Coffea arabica L. oil and Olea europaea L. oil. Two compounds from Coffea arabica L. oil (Chlorogenic acid) and Olea europaea L. oil (Oleuropein) demonstrated good interaction with xanthine oxidase (XO) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) enzymes that are associated with cholesterol production. The present study indicated that Coffea arabica L. oil and Olea europaea L. oil could be considered prospective and potential healing agents against metabolic conditions induced by MAL.

Review of galectin-3 inhibitors in the treatment of nonalcoholic steatohepatitis.

INTRODUCTION: Galectin-3 (Gal-3) is a ß-galactoside binding protein associated with many disease pathologies, including chronic inflammation and fibrogenesis. It has been implicated in the disease severity of NASH, although its precise role is unknown. Inhibition of Gal-3 has shown to improve and prevent fibrosis progression and has now reached phase III clinical trial in NASH patients. AREAS COVERED: This discusses the role of Gal-3 in NASH. It brings together the current findings of Gal-3 in NASH and hepatic fibrosis by analyzing recent data from animal model studies and clinical trials. EXPERT OPINION: Gal-3 inhibitors, in particular, Belapectin (GR-MD-02), have shown promising results for NASH with advanced fibrosis. In a phase 2 trial, Belapectin did not meet the primary endpoint. However, a sub-analysis of Belapectin among a separate group of patients without esophageal varices showed 2 mg/kg of GR-MD-02 reduced HVPG and the development of new varices. A subsequent study is under way, aiming to replicate the positive findings in phase 2 and demonstrate greater efficacy. If Belapectin is shown to be effective, it will be coupled with other drugs that target steatohepatitis to maximize efficacy and disease reversal.

Physiological and histopathological investigations on the effects of alpha-lipoic acid in rats exposed to malathion.

The present study was designed to evaluate the influence of alpha-lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW) for a period of one month. Experimental animals of group 3 were orally given alpha-lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with alpha-lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), alkaline phosphatase (ALP), and acid phosphatase (ACP), and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of alpha-lipoic acid before malathion exposure to rat can prevent severe alterations of hemato-biochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with alpha-lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases.

Therapeutic influences of almond oil on male rats exposed to a sublethal concentration of lead.

Globally, human exposure to heavy metals has risen dramatically. Lead (Pb) is one of the most toxic heavy metals to human and other living organisms. Pb affects certain biochemical and physiological activities of the body. Many scientific investigations have documented the therapeutic and antioxidant properties of natural products which isolated from plant sources. The present study was therefore undertaken to evaluate the therapeutic influence of almond oil against Pb toxicity in male rats. The experimental rats were distributed into four groups. The first group was served as control. The second group was treated with 100 mg/kg body weight of Pb. The third group was subjected to almond oil (800 mg/kg body weight) and Pb. The fourth group was supplemented with almond oil. After six weeks, blood serum specimens were analyzed. In the second group, Pb produced a marked increase of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, glucose, triglycerides, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine, blood urea nitrogen (BUN), uric acid and malondialdehyde (MDA) levels, while the levels of total protein, albumin, high density lipoprotein cholesterol (HDL-C), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased. In contrast, the treatment with almond oil notably improved the biochemical changes and showed antioxidative effect. The present study disclosed the therapeutic influence of almond oil on the basis of its antioxidant effect against Pb toxicity. Moreover, these new findings indicated that the constituents of almond oil have a promising significant potential in biomedical and pharmacological studies.

Effect of Olea europaea leaves extract on streptozotocin induced diabetes in male albino rats.

The present study was aimed to evaluate the effect of olive (Olea europaea) leaves extract on streptozotocin (STZ)-induced diabetic male rats. The experimental rats were divided into six groups. Rats of the first group were served as normal controls. Rats of the second group were diabetic control. The third and fourth groups were diabetic rats, treated with olive leaves extract at low and high doses respectively. The fifth and sixth groups were non diabetic rats, subjected to olive leaves extract at the same doses given to the third and fourth groups respectively. The minimum of body weigh gain was noted in diabetic rats of the second group. the levels of serum glucose, insulin, total protein, albumin, triglycerides, cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), creatine kinase (CK), lactate dehydrogenase (LDH) and malondialdehyde (MDA) were significantly increased, while the levels of high density lipoprotein cholesterol (HDL-C), superoxide dismutase, (SOD) glutathione (GSH) and catalase (CAT) were statistically decreased in diabetic rats of the second group. The levels of liver insulin receptor substrate 1 (IRS1) and insulin receptor A (IRA) were significantly declined in diabetic rats of the second group. The diabetic pancreatic sections from diabetic rats of the second group showed several histopathological changes. Administration of low and high doses of olive leaves extract improved the observed physiological, molecular and histopathological alterations. Collectively, the obtained results confirmed that the protective effects of olive leaves extract are attributed to the antioxidant activities of olive leaves extract and its active constituents.

Influence of olive leaves extract on hepatorenal injury in streptozotocin diabetic rats.

Medicinal plants have always been an important source of new alternative effective compounds for human therapy. Currently, there are many of scientific evidences indicate that the medicinal plants contain a lot of hypoglycemic chemical compounds. The purpose of the present study was to determine the influence of olive leaves extract on hepatorenal injury in diabetic male rats. Experimental diabetes was induced by streptozotocin (STZ). The levels of serum glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine, blood urea nitrogen, uric acid and malondialdehyde were significantly increased, while the levels of serum superoxide dismutase, glutathione and catalase were statistically decreased in untreated diabetic rats. Moreover, the histopathological examination showed several alterations in the structure of liver and kidney in untreated diabetic rats. Treatments with low dose and high dose of olive leaves extract in diabetic rats showed remarkable reducing and protecting influences of physiological and histopathological alterations. Moreover, the highly treatment efficiency was noted in diabetic rats treated with high dose followed by low dose of olive leaves extract. Additionally, the results of this study proved that the antioxidant activities of olive leaves extract played a vital role against the hepatorenal injury induced by diabetes. Finally, this study indicates to the importance of the use of olive leaves extract as promising alternative and complementary therapeutic agent against diabetes and its complications.

Comparative Study on the Influence of Some Medicinal Plants on Diabetes Induced by Streptozotocin in Male Rats.

Medicinal plants have played an important role in the treatment of many diseases. Medicinal plants are believed to be well appropriate with the human body and to produce less side influences than the pharmaceuticals. Kingdom of Saudi Arabia has abundant and wide variety of medicinal plants whose therapeutic effects have not been adequately studied. The aim of this study was to investigate the hypoglycemic activities of the extracts of three plant species collected from Albaha region of Saudi Arabia including Olea oleaster (Oleaceae family) leaves (OLE), Juniperus procera (Cupressaceae family) leaves (JLE), and Opuntia ficus-indica (Cactaceae family) stems (OSE) on streptozotocin (STZ) diabetic male rats. The animals were distributed into eight groups. The first group was used as normal control. The second group was diabetic control. Diabetic rats of the third, fourth, and fifth groups were supplemented with OLE, JLE, and OSE, respectively. Normal rats of the sixth, seventh, and eighth groups were treated with OLE, JLE, and OSE, respectively. As expected, the mean of body weight was significantly decreased in rats of the second group. Significant increase in the value of serum glucose and decline of insulin value were observed in rats of the second group. Several alterations of lipid and protein profile and oxidative stress markers were noted in diabetic control rats. Severe histopathological alterations of pancreatic tissues were observed in untreated diabetic rats. The obtained results showed that OLE, JLE, and OSE attenuated the physiological and histopathological alterations. These new data indicate that the attenuation influences of OLE, JLE, and OSE attributed to their antioxidant properties confirmed by oxidative stress markers evaluation.

Physiological study on the influence of some plant oils in rats exposed to a sublethal concentration of diazinon.

The present study was aimed to evaluate the influence of olive, sesame and black seed oils on levels of some physiological parameters in male rats exposed to diazinon (DZN). Body weight changes, and levels of serum total protein, albumin, glucose, triglycerides, cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), atherogenic index (AI), atherogenic coefficient (AC), cardiac risk ratio (CRR), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MAD) were selected as physiological parameters. The experimental animals were distributed into nine groups. Rats group exposed to DZN and fed with normal diet resulted in pronounced severe changes including reduced body weight gain rate, significantly increase in levels of serum albumin, glucose, cholesterol, LDL-C, AI, AC, CRR and MDA while levels of HDL-C, GSH and SOD were decreased. In rats treated with DZN, the supplementation of the olive, sesame and black seed oils showed remarkable lowering influences of physiological alterations. Moreover, the present results confirmed that these oils possess antioxidative effects against DZN toxicity. Finally, the present findings suggest that these oils are safe and promising agents for the treatment of physiological disturbances induced by DZN and may be also by other pollutants, and toxic and pathogenic factors.

Induction of apoptosis and cell cycle arrest by ethyl acetate fraction of Phoenix dactylifera L. (Ajwa dates) in prostate cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. (Ajwa date) has high nutritive value and are consumed in Arabian Peninsula as an essential diet. Phoenix dactylifera L. have been mentioned in folk remedies of traditional Egyptian medicine and alternative medicine, for numerous health benefits including cancer treatment. The aim of the study is to evaluate the anticancer effects of the extract of Ajwa Date on human Prostate cancer cell line (PC3). MATERIALS AND METHODS: Antiproliferative effect was measured using MTT assay. The long-term effect of EAFAD was determined using colony assay. Different stains like Giemsa and fluorescent stains (DAPI and acridine orange / Ethidium bromide) measured morphological changes. Loss of mitochondrial membrane potential and increased oxidative stress were measured using JC-1 and DCFH-DA dyes. DNA degradation was analyzed by comet assay. Cell cycle distribution was measured by flow cytometer. The apoptotic cell was quantified by annexin V-FITC and Propidium iodide dual staining using flow cytometer. RESULTS: PC3 cell line was treated with ethyl acetate fractions of Ajwa dates (EAFAD) to study their morphological and cellular changes and induction of apoptosis. MTT assay showed the strong inhibitory effect of EAFAD on PC3 cells. Loss of mitochondrial membrane potential and increased oxidative stress were observed in EAFAD treated cells, which suggested mitochondrial involvement in apoptosis. Comet assay proved DNA fragmentation induced by EAFAD. Flow Cytometer results demonstrated that Annexin V-FITC and propidium iodide staining showed that EAFAD induced apoptosis and arrest the cell cycle in S phase. CONCLUSION: Our results suggested EAFAD has potential therapeutics properties for prostate cancer.

Chemoprotective effect of omega-3 fatty acids on thioacetamide induced hepatic fibrosis in male rats.

The current study was designed to investigate the possible protective effect of omega-3 fatty acids from fish oil on hepatic fibrosis induced by thioacetamide (TAA) in male rats. The experimental animals were divided into four groups. The first group was received saline solution and served as control. The second group was given 250 mg/kg body weight of TAA. The third group was treated with omega-3 fatty acids and TAA. The fourth group was given saline solution and supplemented with omega-3 fatty acids. Treatment of rats with TAA for three and six weeks resulted in a significant decrease in body weight gain, while the value of liver/body weight ratio was statistically increased. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and total bilirubin were significantly increased. After three weeks of exposure to only TAA, liver sections showed an abnormal morphology characterized by noticeable fibrosis with the extracellular matrix collagen contents and damage of liver cells' structure. Liver sections from rats treated with only TAA for six weeks revealed an obvious increase in extracellular matrix collagen content and bridging fibrosis. Treating TAA-intoxicated rats with omega-3 fatty acids significantly attenuated the severe physiological and histopathological changes. Finally, the present investigation suggests that omega-3 fatty acids could act against hepatic fibrosis induced by TAA due to its antioxidant properties, thus supporting its use in hepatic fibrosis therapy.

Protective effect of some plant oils on diazinon induced hepatorenal toxicity in male rats.

Environmental pollution and exposure to environmental pollutants are still some of the major global health issues. Pesticides have been linked to a wide range of health hazards. The toxicity of pesticides depends on several factors such as its chemical properties, doses, exposure period, exposure methods, gender, genetics, age, nutritional status and physiological case of exposed individuals. Medicinal plants, natural products and nutrition continue to play a central role in the healthcare system of large proportions of the world's population. Alternative medicine plays an important role in health services around the world. The aim of this study was to investigate the effect of olive, sesame and black seed oils on hepatorenal toxicity induced by diazinon (DZN) in male rats. The experimental animals were divided into nine groups. The first group served as control. The second group was exposed to DZN. The third group was treated with olive oil and DZN. Rats of the fourth group were subjected to sesame oil and DZN. Rats of the fifth group were exposed to black seed oil and DZN. The sixth, seventh and eighth groups were supplemented with olive, sesame and black seed oils respectively. Rats of the ninth group were treated with corn oil. Levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine, blood urea nitrogen and malondialdehyde were significantly increased in rats exposed to DZN. Moreover, levels of serum glutathione and superoxide dismutase were significantly decreased. Several histopathological changes were observed in the structures of liver and kidney due to DZN exposure. This study showed that these oils attenuated the physiological disturbances and histopathological alterations induced by DZN intoxication. Moreover, the antioxidant properties of these oils support the bioactive roles of its protective effects on DZN toxicity. This study therefore suggests that these oils could be used as preventive factors against the toxicity of DZN due to its antioxidant properties.

Protective effect of olive and juniper leaves extracts on nephrotoxicity induced by thioacetamide in male mice.

This study, for the first time, evaluates the effect of olive and juniper leaves extracts and their combination on thioacetamide (TAA)-induced nephrotoxicity in male mice. The experimental mice were divided into eight groups. Group 1 was served as control. Group 2 was exposed to TAA. Group 3 was treated with TAA and olive leaves extract. Group 4 was subjected to TAA and juniper leaves extract. Group 5 was exposed to TAA and olive and juniper leaves extracts. Groups 6, 7 and 8 were treated with olive, juniper, and olive and juniper leaves extracts respectively. In mice treated with only TAA, significant increases of blood urea nitrogen and uric acid were observed after six weeks. Moreover, levels of serum creatinine, blood urea nitrogen and uric acid were statistically increased in mice administrated with only TAA for twelve weeks. Insignificant alterations in levels of these haematobiochemical parameters were noted in other treated groups after six and twelve weeks. Histopathological evaluations of renal sections from mice treated with only TAA for twelve weeks showed severe damage of the renal corpuscles. Furthermore, the renal sections from mice treated with TAA and olive leaves extract, TAA and juniper leaves extract, TAA and olive and juniper leaves extracts, olive leaves extract, juniper leaves extract, and olive and juniper leaves extracts showed normal structures. In addition, it is conceivable therefore, that these extracts exhibit protective influences against TAA-induced nephrotoxicity, probably mediated through the antioxidative pathway roles.