Palm oil amends serum female hormones, ovarian antioxidants, inflammatory markers, and DNA fragmentation in favism-induced female rats.

BACKGROUND: Favism is a metabolic disease and this study evaluates the effectiveness of palm oil and its triacylglycerol constituent in favism-induced female rats to restore serum female hormones, ovarian antioxidants, inflammatory markers, and DNA fragmentation. METHODS: Animals were 36 female albino rats. They classified to two equal (normal and favism) groups. The normal group was divided into three equal subgroups: the control, palm oil, and triacylglycerol subgroups. The normal rats were given 1 mL of saline, 1 mL of palm oil, and 1 mL of triacylglycerol orally, respectively. The Favism group was classified also into three equal subgroups: the favism group, the favism + palm oil, the Favism + triacylglycerol. The favism rats were given 1 mL of saline, 1 mL of palm oil, and 1 mL of triacylglycerol orally. For four weeks, all treatments were administered orally via oral gavage once daily. RESULTS: The hemoglobin, hematocrite, the blood cells, glucose and glucose-6-phosphate dehydrogenase, and liver function were decreased in favism. Female hormones such as serum luteinizing hormone, follicle stimulating hormone, Estrone, Estriol, 17α-Estradiol, 17ß-Estradiol, and Estradiol-17-ß-stearate were decreased in favism. Ovarian antioxidants were decreased while ovarian inflammatory markers were increased in favism. Favism induced ovarian DNA apoptosis. Furthermore, oral administration with palm oil or its triacylglycerol constituent in favism-induced female rats restored all these parameters to be approached the control levels. CONCLUSIONS: Palm oil restored serum female hormones, ovarian antioxidants, inflammatory markers, and DNA fragmentation in favism-induced female rats and this effect related to oil triacylglycerol constituent.

Antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of "dimethyl dimethoxy biphenyl dicarboxylate" in male Wistar rats.

Dimethyl dimethoxy biphenyl (DDB) dicarboxylate has been applied as a therapeutic modality for curing liver diseases, particularly hepatitis virus. The objective of this study was to assess the protective potential against Triton X-100 induced abnormal fat metabolism in addition to anti-inflammatory, analgesic, and antipyretic effects of DDB. The anti-inflammatory, antinociceptive, and antipyretic of DDB were investigated through induction of paw edema, pain, and fever in experimental rats. DDB decreased cholesterol and triglyceride contents. DDB resulted in inhibition of inflammation, nociception, and fever in the experimental models. DDB improved lipid profile, as evidence of hypolipidemic potential. It also showed anti-inflammatory, analgesic, and antipyretic properties.

The involvement of TGF-ß1 /FAK/α-SMA pathway in the antifibrotic impact of rice bran oil on thioacetamide-induced liver fibrosis in rats.

The objective of the current study is to investigate the effect of rice bran oil (RBO) on hepatic fibrosis as a characteristic response to persistent liver injuries. Rats were randomly allocated into five groups: the negative control group, thioacetamide (TAA) group (thioacetamide 100 mg/kg thrice weekly for two successive weeks, ip), RBO 0.2 and 0.4 groups (RBO 0.2mL and 0.4 mL/rat/day, po) and standard group (silymarin 100 mg/kg/day, po) for two weeks after TAA injection. Blood and liver tissue samples were collected for biochemical, molecular, and histological analyses. Liver functions, oxidative stress, inflammation, liver fibrosis markers were assessed. The obtained results showed that RBO reduced TAA-induced liver fibrosis and suppressed the extracellular matrix formation. Compared to the positive control group, RBO dramatically reduced total bilirubin, AST, and ALT blood levels. Furthermore, RBO reduced MDA and increased GSH contents in the liver. Simultaneously RBO downregulated the NF-κß signaling pathway, which in turn inhibited the expression of some inflammatory mediators, including Cox-2, IL-1ß, and TNF-α. RBO attenuated liver fibrosis by suppressing the biological effects of TGF-ß1, α-SMA, collagen I, hydroxyproline, CTGF, and focal adhesion kinase (FAK). RBO reduced liver fibrosis by inhibiting hepatic stellate cell activation and modulating the interplay among the TGF-ß1 and FAK signal transduction. The greater dosage of 0.4 mL/kg has a more substantial impact. Hence, this investigation presents RBO as a promising antifibrotic agent in the TAA model through inhibition of TGF-ß1 /FAK/α-SMA.

Oral supplementation with geranium oil or anise oil ameliorates depressed rat-related symptoms through oils antioxidant effects.

Background Depression is a psychiatric disease condition and the chronic mild stress (CMS) model is a well-known and valuable animal model of depression. Geranium oil and anise oil were chosen for such a study. The aim of this research was to establish the geranium oil and anise oil effect to ameliorate CMS-related symptoms. Methods This research included 80 male albino rats each group of 10 rats and the animals were divided into two major groups: normal and CMS. The normal group was subdivided into four (control, geranium oil, anise oil and venlafaxine drug) subgroups treated orally with saline, geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. The CMS group was subdivided into four (CMS without any treatment, CMS + geranium oil, CMS + anise oil and CMS + venlafaxine drug) subgroups treated orally with geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. Results The sucrose consumption in sucrose preference test, the distance traveled test and center square entries test were decreased, while center square duration test, immobility time in tail suspension test and floating time in forced swimming test were increased in CMS. The superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase levels decreased but malondialdehyde and nitric oxide levels increased in brain cerebral cortex and hippocampus areas in CMS. The oral intake of geranium oil and anise oil pushes all these parameters to approach the control levels. These results were supported by histopathological investigations of both brain cerebral cortex and hippocampus tissues. Conclusions Geranium oil and anise oil ameliorate CMS-related symptoms and this effect were related to the antioxidant effects of oils.

Protective effect of some natural products against chemotherapy-induced toxicity in rats.

AIM: There is a great interest in combining anticancer drugs with natural products aiming at maximizing their efficacy while minimizing systemic toxicity. Hence, the present study was constructed aiming to investigate the protective potential of three natural products, 1,8-cineole an essential oil from Artemisia herba alba, exopolysaccharide (EPS) from locally identified marine streptomycete, and ellagic acid (EA), against chemotherapy-induced organ toxicity. METHODS: Isolation, production and characterization of EPS from marine streptomycete was done. Animals were allocated into five groups, GP1: normal control, GP2: cyclophosphamide (CYC), GP3: 1,8-cineole + CYC, GP4: EPS + CYC, GP4: EA + CYC. All drugs were administered orally 1 week before and concomitantly with CYC. Electrocardiography (ECG) analysis, liver enzymes (ALT and AST), cardiac serum markers (LDH and CK), oxidative stress biomarkers in hepatic and cardiac tissues (GSH and MDA), TGF-ß1 and histopathological examination of hepatic and cardiac tissues were executed. RESULTS: The isolated stain produced EPS was identified as Streptomyces xiamenensis. EPS contains uronic, sulphate groups and different monosugars with Mw 4.65 × 104 g/mol and showed antioxidant activity against DPPH. Pretreatment of rats with 1,8-cineole, EPS and EA improved ECG abnormalities, decrease serum markers of hepato- and cardiotoxicity, prevent oxidative stress and decrease TGF-ß1 in liver and heart tissues. CONCLUSION: The present results demonstrate the hepatoprotective and cardioprotective effects of the above-mentioned natural products against CYC organ toxicity.

Regression of fibrosis by cilostazol in a rat model of thioacetamide-induced liver fibrosis: Up regulation of hepatic cAMP, and modulation of inflammatory, oxidative stress and apoptotic biomarkers.

In liver fibrosis, conversion of fibroblasts to profibrogenic myofibroblasts significantly drives the development of the disease. A crucial role of cyclic adenosine monophosphate (cAMP) in regulation of fibroblast function has been reported. Increase in cAMP levels has been found to decrease fibroblast proliferation, inhibit their conversion to myofibroblast, and stimulate their death. cAMP is generated by adenyl cyclase (AC), and degraded by cyclic nucleotide phosphodiesterase (PDE). In this study, the antifibrotic effect of a PDE inhibitor, cilostazol (Cilo), on a rat model of liver fibrosis induced by thioacetamide (TAA) was investigated. Four groups of rats were used; the first group received the vehicles and served as the normal control group, while liver fibrosis was induced in the other groups using (TAA, 200 mg/kg/biweekly for 8 successive weeks, ip). The last two groups were treated with Cilo (50 and 100 mg/kg/day, po, respectively). Induction of liver fibrosis in TAA-treated rats was observed as evidenced by the biochemical and histopathological findings. On the other hand, a potent antifibrotic effect was observed in the groups treated with Cilo, with preference to the higher dose. In these groups, a significant increase in the liver content of cAMP was demonstrated that was accompanied by reduction in the hepatic expression of key fibrogenic cytokines, growth factors, and inflammatory biomarkers, including interleukin-6, tumor necrosis factor-alpha, nuclear factor kappa B, and transforming growth factor-beta as compared to TAA group. Moreover, amelioration of TAA-induced oxidative stress and apoptosis in the liver has been observed. These findings reveal the antifibrotic effect of Cilo against TAA-induced liver fibrosis in rats, and suggest regulation of cAMP pathway, together with the modulation of oxidative stress, inflammation, and apoptosis as mechanistic cassette underlines this effect.

Antidiarrheal and protein conservative activities of Psidium guajava in diarrheal rats.

OBJECTIVE: Psidium guajava occurs worldwide in tropical and subtropical areas. It has been used to treat inflammation, diabetes, fever, hypertension and ulcers. However, its antidiarrheal and protein conservative activities still need to be investigated. METHODS: Fifty-four male rats were divided into normal and diarrheal rats. The normal rats were divided into 4 groups: control, low-dose P. guajava leaf extract (50 mg/kg), high-dose P. guajava leaf extract (100 mg/kg) and gallic acid. Treatments were administrated orally in 1 mL saline for a 1-month period. The diarrheal rats were divided into 5 groups: desmopressin (0.2 mg/kg) drug, low-dose P. guajava leaf extract (50 mg/kg), high-dose P. guajava leaf extract (100 mg/kg), gallic acid and an untreated control. Doses were given daily for a 1-month period while the untreated control received no treatment. RESULTS: Diarrhea was responsible for an observed decline in kidney weight and serum sodium, potassium and chloride. Further, diarrhea was positively correlated with a significant increase in urine volume, and excretion of electrolytes, serum urea, creatinine and uric acid in the urine. In contrast, there was a proportional increase in the lipid peroxidation value in diarrhea and a significant decline was observed in serum superoxide dismutase, glutathione peroxidase and glutathione levels in diarrhea. Also, diarrhea inhibited blood proteins. The oral intake of P. guajava leaf extract by diarrheal rats restored all of these parameters to near normal levels. High-dose P. guajava leaf extract was more effective than the same compound at a low dose. CONCLUSION: P. guajava leaf extract elicited antidiarrheal and protein conservative effects.

Fertaric Acid Protects from Octylphenol-Related Hepatotoxicity in Rats: Biochemical, Molecular, and Histopathological Studies.

The endocrine-disrupting chemical 4-tert-octylphenol (OP) can mimic estrogen and testosterone hormones and threaten health; fertaric acid (FA) is a hydroxycinnamic acid found in grapefruit. This study aimed to investigate whether FA has a protective effect on 4-tert-octylphenol-related hepatotoxicity. Thirty male albino rats were divided into 5 equal groups of 6 rats each as follows: control group-administrated orally with 1 ml saline 3 days/week for 4 weeks; corn oil group-administrated orally with 1 ml corn oil 3 days/week for 4 weeks; FA-treated group-administrated orally with FA (45 mg /kg body weight) dissolved in saline 3 days/week for 4 weeks; OP-treated group-administrated orally with OP (40 mg /kg body weight) dissolved in corn oil 3 days/week for 4 weeks; FA + OP-treated group-administrated orally with FA (45 mg /kg body weight) dissolved in saline 3 days/week for 4 weeks then administrated orally with OP (40 mg/kg body weight) dissolved in corn oil 3 days/week for another 4 weeks. The results obtained showed that OP-exposed rats had significant increase in serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, lactate dehydrogenase, bilirubin, serum and liver tumor necrosis factor-α, interleukin-1ß and malondialdehyde, serum interleukin-6 and interleukin-10 and significant decrease in serum alkaline phosphatase, acid phosphatase, serum and liver superoxide dismutase, glutathione peroxidase, and catalase. OP caused an inhibitory action on the gene expression of liver proteins. Rats treated with FA before OP exposure had near-normal values. In addition, FA prevented the degradation of liver deoxyribonucleic acid (DNA), and DNA reformation occurred. In conclusion, FA protects from dangerous OP-related hepatic effects, and these results were supported by molecular and histological investigations.

Acute and subacute toxicity of Ammi visnaga on rats.

Ammi visnaga (Av) is a source of khellin where a tea made from the fruit of this plant was used as herbal medicine for kidney stones in Egypt. In the present research, the acute and subacute toxicity studies with oral intake of 150, 300 and 600 mg/kg of Av seed ethanolic extract in rats were done. In acute toxicity test, 4 groups of rats (n = 6/group: 3 males and 3 females) were chosen and the first control group received tap water, while the other three groups received Av seed ethanolic extract dissolved in tap water at doses of 150, 300, and 600 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, 72 rats (36 males and 36 females) were divided into 4 major groups; group I received tap water (control group), while animals in groups II, III, and IV (test groups) received oral intake of Av seed ethanolic extract dissolved in tap water at doses of 150, 300 and 600 mg/ kg bwt, respectively. Each of this major group was subdivided consequently into 3 subgroups (n = 6/group: 3 males and 3 females) where brain tissue, blood sample, body and organs weights were recorded at the beginning and then after two and four weeks of the experiment for the determination of hematological, biochemical and histopathological changes in tissues (liver, kidney, brain, spleen, heart, testis and ovary). With regard to acute toxicity, Av seed ethanolic extract did not induce any toxic effects or death or any organ toxicity. In subacute toxicity study; oral intake with Av seed ethanolic extract did not reveal any change in body and organs weights, hematological parameters, serum glucose and cholesterol, brain neurotransmitters, liver and kidney functions, male and female hormones. In conclusion, Av seed ethanolic extract is nontoxic to liver, kidney, brain, spleen, heart, testis and ovary.

The Role of Chlorogenic Acid Supplementation in Anemia and Mineral Disturbances Induced by 4-Tert-Octylphenol Toxicity.

4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful effects to human health. Chlorogenic acid is the major dietary polyphenol present in various foods and beverages. The aim of the present study was to evaluate the protective role of chlorogenic acid in anemia and mineral disturbance occurring in OP toxicity in rats. Thirty-two male albino rats were divided into four equal groups (8 rats/group) as follows. The first (control) group was treated daily with an oral dose of 1 ml saline for two weeks. The second group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks. The third and fourth groups received daily intraperitoneal (ip) injections with 100 mg OP/kg body weight for two weeks; the fourth group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting one week before OP injections. The results revealed that OP induced significant decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium, phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover, significant increases in serum hepcidin, ferritin, transferrin, erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis. Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned parameters to approach the normal values. In conclusion, chlorogenic acid protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by ameliorating oxidative stress and apoptosis.

Role of caftaric acid in lead-associated nephrotoxicity in rats via antidiuretic, antioxidant and anti-apoptotic activities.

Background Lead is a toxic metal that is widely distributed in the environment where caftaric acid (CA) is the ester form of caffeic acid where CA is the major dietary polyphenol present in various foods and beverages. The aim of this study was to evaluate the effect of CA in lead acetate (LA)-associated nephrotoxicity through antidiuretic, antioxidant and anti-apoptotic activities. Methods Forty-eight male albino rats divided into six equal groups; group 1 control injected intraperitoneally (ip) with saline (1 mL/kg of bw) over two weeks period, group 2 injected ip with CA (80 mg/kg of bw) over two weeks period, groups 3, 4, 5 and 6 injected ip with 100 µmol/kg of bw LA over two weeks period where groups 4, 5 & 6 co-injected ip with 1-deamino-8-D-arginine vasopressin (dDAVP) drug (1 mg/kg of bw), CA (40 mg/kg of bw), and CA (80 mg/kg of bw), respectively. Results The results obtained revealed that LA induced a significant decrease in kidney weight and serum sodium, potassium and chloride, but caused a significant increase in urinary volume, urinary excretion of sodium, potassium and chloride, serum urea, creatinine and uric acid. The LA also caused a significant decrease in kidney superoxide dismutase, glutathione peroxidase and induced a significant decrease in glutathione level while caused an increase in lipid peroxidation level. In addition, LA caused a decrease in p53 expression while induced an increase in bcl-2 expression in the kidney tissues. Co-injection of CA to LA-treated group restored all the above parameters to approach the normal values. The results supported with histopathological examinations. Conclusions In conclusion, the effect of CA on LA-related nephrotoxicity was occurred through antidiuretic, antioxidant, anti-apoptotic activities where the effect of CA was dose dependent.

Supplementation of α-Tocopherol Attenuates Minerals Disturbance, Oxidative Stress and Apoptosis Occurring in Favism.

The favism is a metabolic disease that characterized with an acute hemolytic anemia where α-tocopherol is a type of tocopherol accumulated inside the human body. The objective of such a study was established to evaluate the effect of α-tocopherol in favism disorders. A total of 75 human cases were divided into 5 groups as follow; group 1 normal cases without any treatment and group 2 normal cases orally administrated α-tocopherol (200 mg/kg) once a day over 30 days period. Group 3 favism patients without any treatment. Groups 4 and 5 favism patients orally administrated 100 and 200 mg α-tocopherol/kg, respectively once a day over 30 days period. The results obtained revealed that oral administration of α-tocopherol into normal cases over 30 days period did not induce any biological change. In favism, hemoglobin, hematocrit, red and white blood cells, serum glucose, glucose-6-phosphate dehydrogenase, total protein, albumin, globulin, aspartate and alanine aminotransferases, blood glutathione, superoxide dismutase, glutathione peroxidase and serum calcium, phosphorous, sodium, potassium and chloride levels were significantly decreased. On the other hand, serum alkaline phosphatase, bilirubin, selenium, zinc, manganese, copper and iron, malondialdehyde levels showed significant increase in favism. Supplementation with α-tocopherol into favism restores all the above mentioned parameters to approach the normal levels. Also, α-tocopherol has anti-apoptotic effect in favism. In conclusion, α-tocopherol attenuates minerals disturbance, oxidative stress and apoptosis occurring in favism.

Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

The Protective Role of Anise Oil in Oxidative Stress and Genotoxicity Produced in Favism.

The metabolic disease favism is an acute hemolytic anemia. Anise oil was obtained from Pimpinella anisum L. seeds (family Apiaceae). The objective of this study was to establish the protective effect of anise oil in favism disorders. Forty-eight male albino rats were divided into six groups: group 1 orally administrated 1 mL distilled water, group 2 orally received 300 mg/kg anise oil, and group 3 orally administrated 100 mg/kg anethole over a seven-day period, group 4 favism-induced rats, group 5 orally administrated 300 mg/kg anise oil and group 6 orally administrated 100 mg/kg anethole once a day over a seven-day period prior to favism induction. The result obtained revealed that oral administration of either anise oil or anethole into normal rats over a seven-day period did not induce any change. Following favism induction, hemoglobin, hematocrit, red and white blood cell counts, serum glucose, blood glutathione, glucose-6-phosphate dehydrogenase, total protein, globulin, alanine and aspartate aminotransferases levels were significantly decreased, while serum alkaline phosphatase and bilirubin showed significant increase. Pretreatment with either anise oil or anethole into favism-induced rats prevented these changes. Favism also induced deoxyribonucleic acid (DNA) damage and prior treatment of anise oil maintained liver DNA content. These results were supported by histopathological evaluation. In conclusion, anise oil pretreatment into favism-induced rats decreased the favism disorders, and this effect was related to the anethole ingredient of the oil.

Therapeutic effect of pectin on octylphenol induced kidney dysfunction, oxidative stress and apoptosis in rats.

Octylphenol (OP) is one of ubiquitous pollutants in the environment. It belongs to endocrine-disrupting chemicals (EDC). It is used in many industrial and agricultural products. Pectin is a family of complex polysaccharides that function as a hydrating agent and cementing material for the cellulose network. The aim of this study was to evaluate the therapeutic effect of pectin in kidney dysfunction, oxidative stress and apoptosis induced by OP exposure. Thirty-two male albino rats were divided into four equal groups; group 1 control was injected intraperitoneally (i.p) with saline [1 ml/kg body weight (bwt)], groups 2, 3 & 4 were injected i.p with OP (50 mg/kg bwt) three days/week over two weeks period where groups 3 & 4 were injected i.p with pectin (25 or 50 mg/kg bwt) three days/week over three weeks period. The results of the present study revealed that OP significantly decreased glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) levels while increased significantly lipid peroxidation (MDA), nitric oxide (NO) and protein carbonyls (PC) levels in the kidney tissues. On the other hand, OP increased serum urea and creatinine. Furthermore, OP increased significantly serum uric acid but decreased significantly the kidney weight. Moreover, OP decreased p53 expression while increased bcl-2 expression in the kidney tissue. The treatment with either dose of pectin to OP-exposed rats restores all the above parameters to approach the normal values where pectin at higher dose was more effective than lower one. These results were supported by histopathological investigations. In conclusion, pectin has antioxidant and anti-apoptotic activities in kidney toxicity induced by OP and the effect was dose-dependent.

Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of insulin and adiponectine receptors, Tyrosine kinase, PI3K, glucose transporters, sRAGE and visfatin in insulin resistant/diabetic rats.

UNLABELLED: As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in several models of diabetes and/or insulin resistance (IR); however, its exact mechanisms have not been profoundly explicated. Hence, the objective of this work is to verify some of the possible mechanisms that underlie its therapeutic efficacy. Moreover, the study aimed to assess the potential modulatory effect of CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2 diabetic model was adopted, in which rats were fed high fat/high fructose diet (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin (35 mg/kg, i.p.). At the end of the 7(th) week animals were treated with CoQ10 (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone opposed the HFFD effect and increased the hepatic/muscular content/activity of tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin receptors. Conversely, it decreased the content/activity of insulin receptor isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA index, improved the serum lipid panel and elevated the levels of glutathione, sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that of glimepiride in almost all the assessed parameters, except for glucose, fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the effect of the latter on the aforementioned parameters. CONCLUSION: These results provided a new insight into the possible mechanisms by which CoQ10 improves insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms involve modulation of insulin and adiponectin receptors, as well as TK, PI3K, glucose transporters, besides improving lipid profile, redox system, sRAGE, and adipocytokines. The study also points to the potential positive effect of CoQ10 as an adds- on to conventional antidiabetic therapies.

Safety evaluation of a bioglass-polylactic acid composite scaffold seeded with progenitor cells in a rat skull critical-size bone defect.

Treating large bone defects represents a major challenge in traumatic and orthopedic surgery. Bone tissue engineering provides a promising therapeutic option to improve the local bone healing response. In the present study tissue biocompatibility, systemic toxicity and tumorigenicity of a newly developed composite material consisting of polylactic acid (PLA) and 20% or 40% bioglass (BG20 and BG40), respectively, were analyzed. These materials were seeded with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) and tested in a rat calvarial critical size defect model for 3 months and compared to a scaffold consisting only of PLA. Serum was analyzed for organ damage markers such as GOT and creatinine. Leukocyte count, temperature and free radical indicators were measured to determine the degree of systemic inflammation. Possible tumor occurrence was assessed macroscopically and histologically in slides of liver, kidney and spleen. Furthermore, the concentrations of serum malondialdehyde (MDA) and sodium oxide dismutase (SOD) were assessed as indicators of tumor progression. Qualitative tissue response towards the implants and new bone mass formation was histologically investigated. BG20 and BG40, with or without progenitor cells, did not cause organ damage, long-term systemic inflammatory reactions or tumor formation. BG20 and BG40 supported bone formation, which was further enhanced in the presence of EPCs and MSCs. This investigation reflects good biocompatibility of the biomaterials BG20 and BG40 and provides evidence that additionally seeding EPCs and MSCs onto the scaffold does not induce tumor formation.

Effect of the antibiotic neomycin on the toxicity of the glycoside vicine in rats.

Vicine is hydrolyzed by microflora to highly reactive free radical generating compound divicine which causes mortality and other adverse effects. This study in the rats established the effect of a broad spectrum and poorly absorbed antibiotic, neomycin sulfate on the toxicity of vicine. The results showed extremely decrease in mortality rate in the group pretreated with neomycin. Hemoglobin (Hb) concentration, hematocrit (Hct) value, and red blood cells (RBCs) count were significantly decreased after injection of vicine and the improvement of these values in the group pretreated with neomycin. The same results were observed in white blood cells (WBCs). The results showed a significant decrease in glucose level and returned to normal in group pretreated with neomycin. Glutathione (GSH) was significantly decreased in the vicine group and returned to normal value in the group pretreated with neomycin. Lipid peroxide (TBARs) was significantly increased in the group treated with vicine and neomycin pretreated group decreased to the normal level. Glucose-6-phosphate dehydrogenase (G6-PD) activity was significantly decreased and returned to normal level in rats pretreated with neomycin. Serum protein and globulin were significantly decreased but serum albumin showed insignificant decrease in vicine and neomycin groups compared to control. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased in the vicine group. The group pretreated with neomycin showed significantly increased activities of AST and ALT compared with vicine group. In conclusion, neomycin pretreatment of rats injected with glycoside vicine decreased to a great extent of its toxic and mortality effects and is useful in favism and hemolytic anemia.

Chelidonium majus leaves methanol extract and its chelidonine alkaloid ingredient reduce cadmium-induced nephrotoxicity in rats.

The kidney is one of the critical target organs for chronic cadmium toxicity. Cadmium is a cumulative nephrotoxicant, and preferentially accumulates and persists in the kidneys. The natriuretic and antidiuretic effects of methyl alcohol extracts of Chelidonium majus L. (C. majus) leaves were evaluated in kidney of cadmium-intoxicated rats. Ninety-six male Sprague-Dawley Albino rats were divided into two major groups (toxicity and biochemical, 60 and 36 rats, respectively). There was a decrease in kidney weight and serum electrolytes, but an increase in urinary volume, excretion of electrolytes, serum urea and creatinine, after 9 weeks of cadmium chloride intoxication. Treatment of C. majus methyl alcohol extract for 10 weeks starting 1 week before cadmium administration shifted the above parameters towards the normal values. These results were supported by molecular and histological investigations. Treatment with C. majus methyl alcohol extract has natriuretic and antidiuretic effects against cadmium-induced nephrotoxicity in rats.