LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes.

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy.

Role of long noncoding RNAs; BDNF-AS and 17A and their relation to GABAergic dysfunction in Egyptian epileptic patients.

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures. Lately, long noncoding RNAs (lncRNAs) have been increasingly appreciated as regulators of epilepsy-related processes, however, their functional role in its pathogenesis is still to be explored. This study investigated the expression levels of lncRNAs; BDNF-AS and 17A in the sera of Egyptian patients with idiopathic generalized and symptomatic focal epilepsy and correlated their levels with brain-derived neurotrophic factor (BDNF), phosphorylated cAMP reaction element -binding protein (p-CREB), gamma- aminobutyric acid (GABA) and glutamate, to underline their related molecular mechanism. A total of 70 epileptic patients were divided into two clinical types, besides 30 healthy controls of matched age and sex. The expression levels of both lncRNAs were markedly upregulated in epileptic groups versus the healthy control group with predominance in the symptomatic focal one. Epileptic patients showed significantly lower levels of BDNF, p-CREB, GABA along with significant increase of glutamate levels and glutamate/ GABA ratio, especially in symptomatic focal versus idiopathic generalized epileptic ones. The obtained data raised the possibility that these lncRNAs might be involved in the pathogenesis of epilepsy via inhibition of GABA/p-CREB/BDNF pathway. The study shed light on the putative role of these lncRNAs in better diagnosis of epilepsy, particularly symptomatic focal epilepsy.

Ameliorating effect of ketogenic diet on acute status epilepticus: Insights into biochemical and histological changes in rat hippocampus.

This study aimed to evaluate the potential neuroprotective effects of ketogenic diet (KD) against the neuronal disruptions induced by SE in lithium-pilocarpine rat model of status epilepticus (SE). Four groups of female rats include; groups I and III received standard diet and groups II and IV received KD for 3 weeks. Groups I and II were left untreated, while groups III and IV were injected with LiCl (127 mg/kg, i.p.) followed by pilocarpine HCl (10 mg/kg, i.p.) 18-24 h later, repeatedly, till induction of SE. 72 h post-SE, KD effectively ameliorated the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters and the oxidative stress indices, increased adenine nucleotides and decreased immunoreactivity of iNOS, TNFα, glial fibrillary acidic protein, and synaptophysin. Thiswas in association with improvement in inflammatory response and neuronal tissue characteristics in hippocampus of SE rats. Histological changes showed preservation of neuronal integrity. These findings highlight the protective effects of KD in the acute phase post-SE via ameliorating biochemical and histological changes involved. PRACTICAL APPLICATIONS: Epilepsy is the fourth most common neurological disorder that requires lifelong treatment. It stigmatizes patients and their families. The use of the ketogenic diet (KD) as a therapy for epilepsy developed from observations that fasting could reduce seizures. From 1920s, the KD was a common epilepsy treatment until it was gradually superseded by anticonvulsant drugs so that by the 1980s it was rarely used. However, there has been a resurgence of interest and usage of the KD for epilepsy since the turn of the century. Despite its long history, the mechanisms by which KD exhibits its anti-seizure action are not fully understood. Our study aims to identify the mechanism of KD which may help further studies to achieve the same benefits with a drug or supplement to overcome its unpalatability and gastrointestinal side effects.

Circulating lncRNAs HIF1A-AS2 and LINLK-A: Role and Relation to Hypoxia-Inducible Factor-1α in Cerebral Stroke Patients.

Long noncoding RNAs (lncRNAs) have been recently recognized as key players of gene expression in cerebral pathogenesis. Thus, their potential use in stroke diagnosis, prognosis, and therapy is actively pursued. Due to the complexity of the disease, identifying stroke-specific lncRNAs remains a challenge. This study investigated the expression of lncRNAs HIF1A-AS2 and LINK-A, and their target gene hypoxia-inducible factor-1 (HIF-1) in Egyptian stroke patients. It also aimed to determine the molecular mechanism implicated in the disease. A total of 75 stroke patients were divided into three clinical subgroups, besides 25 healthy controls of age-matched and sex-matched. Remarkable upregulation of lncRNA HIF1A-AS2 and HIF1-α along with a downregulation of lncRNA LINK-A was noticed in all stroke groups relative to controls. Serum levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt (p-Akt), vascular endothelial growth factor (VEGF), and angiopoietin-1 (ANG1) as well as their receptors, malondialdehyde (MDA), and total antioxidant capacity (TAC) were significantly increased, whereas brain-derived neurotrophic factor (BDNF) levels were significantly decreased particularly in hemorrhagic stroke versus ischemic groups. Eventually, these findings support the role of lncRNAs HIF1A-AS2 and LINK-A as well as HIF1-α in activation of angiogenesis, neovascularization, and better prognosis of stroke, especially the hemorrhagic type.

Serum ROCK2, miR-300 and miR-450b-5p levels in two different clinical phenotypes of multiple sclerosis: Relation to patient disability and disease progression.

Relapsing remitting multiple sclerosis (RRMS) is the most prevalent MS subtype. Years after disease onset, most of RRMS patients show transition into secondary progressive form (SPMS). Currently, no biomarkers are available for tracking disease progression. Here, we observed marked elevation of Rho-associated protein kinase 2 (ROCK2) along with significant downregulation of miRNAs 300 and 450b-5p expressions in the serum of 39 RRMS and 35 SPMS Egyptian patients compared to healthy controls. More pronounced alterations were found in SPMS versus RRMS patients. Our findings also suggest relations between elevated ROCK2 and reduced expression of both miRNAs with the degree of disability and disease progression. Notably, these biomarkers effectively discriminated RRMS from SPMS patients with miR-450b-5p showing the highest prognostic power.

Long noncoding RNAs APOA1-AS, IFNG-AS1, RMRP and their related biomolecules in Egyptian patients with relapsing-remitting multiple sclerosis: Relation to disease activity and patient disability.

Lately, long noncoding (lnc) RNAs are increasingly appreciated for their involvement in multiple sclerosis (MS). In inflammation and autoimmunity, a role of apoprotein A1 (ApoA1), mediated by sphingosine 1-phosphate receptors (S1PRs), was reported. However, the epigenetic mechanisms regulating these biomolecules and their role in MS remains elusive. This case control study investigated the role of ApoA1, sphingosine kinase 1 and 2 (SPHK1 & 2), S1PR1 & 5, interferon-γ (IFN-γ) and interleukin 17 (IL17) in MS, beside three lncRNA: APOA1-AS, IFNG-AS1, and RMRP. Expression of SPHKs, S1PRs, and lncRNAs were measured in 72 relapsing-remitting MS patients (37 during relapse and 35 in remission) and 28 controls. Plasma levels of ApoA1, IFN-γ and IL17 were determined. The impact of these parameters on MS activity, relapse rate and patient disability was assessed. APOA1-AS, IFNG-AS1, SPHK1 & 2, and S1PR5 were upregulated in RRMS patients. Differences in ApoA1, SPHK2, and IL17 were observed between relapse and remission. Importantly, ApoA1, SPHK2, and IL17 were related to activity, while S1PR1 and IFN-γ were linked to disability, though, only IFN-γ was associated with relapse rate. Finally, an excellent diagnostic power of IFN-γ, IL17, SPHK1 and APOA1-AS was demonstrated, whereas SPHK2 showed promising prognostic power in predicting relapses.

Hydrogen sulfide enhances the effectiveness of mesenchymal stem cell therapy in rats with heart failure: In vitro preconditioning versus in vivo co-delivery.

Stem cell therapy represents a promising therapeutic avenue for cardiac disorders, including heart failure. Although stem cell transplantation showed encouraging preliminary results, the outcomes of clinical studies are still unsatisfactory. This study aimed to compare the outcomes of two therapeutic approaches, in vivo co-delivery of sodium hydrogen sulfide (NaHS) concomitant with bone marrow-derived mesenchymal stem cell (BMSC) transplantation and in vitro preconditioning of BMSCs with NaHS, both of which are intended to promote the success of stem cell therapy in rats with isoprenaline-induced heart failure. Heart failure developed 4 weeks after the subcutaneous injection of isoprenaline (170 mg/kg) for 4 consecutive days. The in vivo approach involved the co-delivery of intraperitoneally administered NaHS concomitant with BMSC transplantation for a period of 14 days. The in vitro approach involved preconditioning BMSCs with NaHS for 30 min before transplantation. Compared to treatment with BMSCs alone, in vitro preconditioning of BMSCs with NaHS improved left ventricular function as measured by echocardiography and electrocardiography and enhanced stem cell homing, proliferation and differentiation as manifested by higher cardiac expression of GATA-4 and myocyte enhancer factor 2. Moreover, the measurement of cardiac transforming growth factor beta 1 levels and histopathological investigation revealed mitigated fibrosis and myocardial injury scores. Compared with BMSC therapy alone, the in vivo approach enhanced stem cell homing and differentiation, alleviated fibrosis and augmented vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression. In conclusion, NaHS can potentiate the efficiency of BMSC therapy for heart failure by in vitro preconditioning or in vivo co-delivery. The in vitro approach is superior with regard to improving cardiac function in addition to enhancing stem cell proliferation, while the in vivo approach is superior with regard to increasing cardiac VEGF and eNOS expression.

Association between endoglin/transforming growth factor beta receptors 1, 2 gene polymorphisms and the level of soluble endoglin with preeclampsia in Egyptian women.

INTRODUCTION: Preeclampsia (PE) is a pregnancy-specific hypertensive disease whose etiopathogenesis remains unclear. OBJECTIVES: This study was designed to assess association between PE and 3 single nucleotide polymorphisms (SNPs): ENG(G/A) rs11792480, TGFßR1(A/C) rs10739778 and TGFßR2(G/A) rs6550005, beside circulating soluble endoglin (sENG), oxidative stress biomarkers and nitric oxide (NO) in Egyptian women. METHODS: The study included 75 preeclamptic women stratified into 4 clinical subgroups and 50 normotensive pregnant women. Genotyping was performed by real time polymerase chain reaction-Taqman allelic discrimination. RESULTS: Preeclamptic women showed significantly increased sENG and malondialdehyde (MDA), decreased total antioxidant capacity (TAC), endothelial nitric oxide synthase (eNOS) and NO, without change in transforming growth factor beta 1 (TGFß1) versus controls. Moreover, sENG was significantly higher in severe and early than mild and late PE. Higher MDA and lower TAC and NO were observed in severe than mild PE. ENG(G/A) and TGFßR2(G/A) showed no association with PE. However, CC genotype of TGFßR1(A/C) was more frequent in controls than either PE, early-onset or severe revealing a reduced PE risk in CC genotype versus AA or AA + AC. Importantly, patients carrying AA genotype had higher SBP and MDA with lower TAC, gestational age at delivery (GA) and birth weight than those carrying CC genotype. CONCLUSIONS: Excessive sENG release with decreased eNOS/NO may be involved in PE pathogenesis. Women who carry C allele or CC genotype of TGFßR1(A/C) may be less prone to develop PE.

Role of long non-coding RNAs expression (ANRIL, NOS3-AS, and APOA1-AS) in development of atherosclerosis in Egyptian systemic lupus erythematosus patients.

To quantify the expression level of three lncRNAs which are known to be relevant to atherosclerosis (ANRIL, NOS3-AS, and APOA1-AS) in SLE patients and to assess their relationship with atherogenic and inflammatory biomarkers. The circulating levels of these lncRNAs were assessed using RT-PCR, in addition to measurement of E-selectin, V-CAM1, oxidized low-density lipoprotein (oxLDL), total nitric oxide (NOx), and lipid profile in 65 SLE patients (35 atherosclerotic and 30 non-atherosclerotic) and 35 healthy subjects. The expression levels of these lncRNAs were higher in SLE patients than in healthy controls. Importantly, a higher overexpression of these lncRNAs was noticed in atherosclerotic SLE patients than in non-atherosclerotic ones. In atherosclerotic SLE patients, level of ANRIL was positively associated with menopause, SLE duration, SLEDAI, and SLICC and negatively correlated with C3. Moreover, NOS3-AS expression was negatively correlated with total NOx level and HDL, while it was positively correlated with TC, LDL-C, hypertension, metabolic syndrome, obesity and dyslipidemia, CIMT, VCAM-1, E-selectin, oxLDL, SLEDAI, and SLICC. With respect to APOA1-AS, its expression was negatively correlated with HDL-C, whereas it was positively correlated with TC, LDL-C, hypertension, dyslipidemia, obesity, metabolic syndrome, menopause, CIMT, RI, V-CAM1, E-selectin, oxLDL, and SLICC. ANRIL, NOS3-AS, and APOA1-AS could be used as predictive biomarkers for atherosclerosis in SLE. Multivariate analyses identified these lncRNAs as independent predictors for atherosclerosis in SLE. These lncRNAs play a pivotal role in development of atherosclerosis via their significant repercussions atherogenic and inflammatory indices.

Resveratrol Promotes Remyelination in Cuprizone Model of Multiple Sclerosis: Biochemical and Histological Study.

Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice. Mice were fed with chow containing 0.7 % cuprizone for 7 days, followed by 3 weeks on 0.2 % cuprizone diet. Resveratrol (250 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. At the end of the experiment, animals were tested on rotarod to evaluate changes in balance and motor coordination. Mice were then sacrificed to measure the brain content of glutathione, lipid peroxidation products, adenosine triphosphate, and phospho-inhibitory subunit of nuclear factor κB-α. The activities of cytochrome oxidase and superoxide dismutase were also assessed. The gene expression of myelin basic protein, 2',3'-cyclic nucleotide 3' phosphodiesterase, oligodendrocyte transcription factor-1 (Olig1), NF-κB p65 subunit, and tumor necrosis factor-α was also estimated. Luxol fast blue/periodic acid-Schiff stained brain sections were blindly scored to assess the myelin status. Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination, improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. Interestingly, resveratrol increased Olig1 expression that is positively correlated to active remyelination. The present study may be the first to indicate a pro-remyelinative effect for resveratrol which might represent a potential additive benefit in treating MS.

Impact of Genetic Polymorphism of methylenetetrahydrofolate reductase C677T on Development of Hyperhomocysteinemia and Related Oxidative Changes in Egyptian ß-Thalassemia Major Patients.

BACKGROUND: ß-thalasemia major (ß-TM) patients often suffer from various vascular complications together with increased oxidative stress. Hyperhomocysteinemia (Hhcy) has been defined as a risk factor for these complications. Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to cause Hhcy particularly in individuals with low B-vitamins. However, the status of homocysteine (hcy) in ß-TM has not yet been adequately defined. AIM: To evaluate the genetic polymorphism of MTHFR C677T among ß-TM patients and its prospective contribution to Hhcy and related oxidative changes. SUBJECTS AND METHODS: Genotyping for MTHFR C677T was done by PCR-RFLP technique. Plasma hcy, vitamin B12, folate, malondialdehyde (MDA), total antioxidant capacity (TAC), oxidized low density lipoprotein (oxLDL), total nitric oxide (NOx) and lipid profile were determined in 66 ß-TM patients and 66 control subjects of matched age and sex. RESULTS: The prevalence of MTHFR 677TT genotype was significant among ß-TM patients (12%) compared to (3%) controls (OR = 4.9, 95%CI:1.2-24.2,P = 0.03). A strong association between Hhcy and MTHFR TT genotype was observed (OR = 7.7, 95%CI:2.8-20.9) where all ß-TM patients with TT genotype were hyperhomocystienemic (≥ 15 µmol/l) and having sub-optimal folate level than those with CT or CC genotypes. Hyperhomocystienemic patients have suffered from increased oxidative stress characterized by significant increase in plasma MDA and oxLDL, and a significant reduction of plasma TAC and total NOx. Lipid profile of those patients was severely affected indicated by reduction in HDL and HDL/LDL and elevation in atherogenic index as compared with CC genotype. Other measured parameters were not significantly different among ß-TM patients with different MTHFR genotypes. CONCLUSION: This study suggests that Egyptian ß-TM patients with MTHFR 677TT genotype could be at increasing risk of developing Hhcy particularly with folate deficiency. This state of Hhcy may account potentially for most oxidative changes and atherogenic vascular complications frequently reported in ß-TM patients.

Avemar and Echinacea extracts enhance mobilization and homing of CD34(+) stem cells in rats with acute myocardial infarction.

INTRODUCTION: Activation of endogenous stem cell mobilization can contribute to myocardial regeneration after ischemic injury. This study aimed to evaluate the possible role of Avemar or Echinacea extracts in inducing mobilization and homing of CD34(+) stem cells in relation to the inflammatory and hematopoietic cytokines in rats suffering from acute myocardial infarction (AMI). METHODS: AMI was developed by two consecutive subcutaneous injections of isoprenaline (85 mg/kg). AMI rats were either post-treated or pre- and post-treated daily with oral doses of Avemar (121 mg/kg) or Echinacea (130 mg/kg). In whole blood, the number of CD34(+) cells was measured by flow cytometry and their homing to the myocardium was immunohistochemically assessed. Serum creatine kinase, vascular endothelial growth factor, interleukin-8 and granulocyte macrophage colony stimulating factor were determined on days 1, 7 and 14 after AMI. Sections of the myocardium were histopathologically assessed. RESULTS: Rats pre- and post-treated with Avemar or Echinacea exhibited substantial increases in the number of circulating CD34(+) cells, peaking on the first day after AMI to approximately 13-fold and 15-fold, respectively, with a decline in their level on day 7 followed by a significant increase on day 14 compared to their corresponding AMI levels. Only post-treatment with Echinacea caused a time-dependent increase in circulating CD34(+) cells on days 7 and 14. Such increases in circulating CD34(+) cells were accompanied by increased homing to myocardial tissue 14 days after AMI. Interestingly, pre- and post-treatment with Avemar or Echinacea substantially increased serum creatine kinase on day 1, normalized its activity on day 7 and, on continued treatment, only Echinacea markedly increased its activity on day 14 compared to the corresponding AMI values. Moreover, both treatments modified differently the elevated serum vascular endothelial growth factor and the lowered granulocyte macrophage colony stimulating factor levels of the AMI group but did not affect the level of interleukin-8. These results were supported histopathologically by reduced inflammatory reactions and enhanced neovascularization. CONCLUSION: Avemar and Echinacea extracts can effectively induce mobilization and homing of CD34(+) stem cells to the myocardial tissue and thus may help in stem cell-based regeneration of the infarcted myocardium.

Propolis enhances the effectiveness of praziquantel in experimental schistosomiasis: biochemical and histopathological study.

Despite the wide current use of praziquantel (PZQ) in treatment of schistosomiasis, low cure rates have been recorded in many studies. The aim of this study was directed to evaluate the curative effect of propolis (Pps) alone or in combination with PZQ on biochemical, immunological, parasitological, and histological changes associated with experimental schistosomiasis in mice. Schistosoma mansoni-infected mice were divided into two experimental sets, each with four subgroups: (i) untreated, (ii) treated with Pps/day p.o for 4 weeks, (iii) treated with PZQ p.o 2 × 500 mg/kg bd wt, and (iv) treated with Pps + PZQ as in group ii and iii; all treatments started on the 8th week postinfection, in addition to uninfected group as control for the previous groups. Treatment of infected mice with Pps, although failed to eradicate the worm, significantly reduced the hepatic granuloma number, their lymphocytic infiltration and aggregation, hepatic and splenic myeloperoxidase (MPO) activity and plasma, and liver and thymus nitric oxide (NOx) levels together with normalization of plasma proteins and alleviation of oxidative stress in the examined tissues as evidenced by reduction of malondialdehyde (MDA) and normalization of glutathione (GSH). Promising results were obtained when Pps was given in combination with PZQ, where the anti-schistosomal activity of PZQ was markedly potentiated with complete alleviation and amelioration of the histological and biochemical alteration associated with schistosomiasis. This study highlights the potential usefulness of Pps as an adjunct to PZQ in schistosomiasis.

Pretreatment with turmeric modulates the inhibitory influence of cisplatin and paclitaxel on CYP2E1 and CYP3A1/2 in isolated rat hepatic microsomes.

Previous animal studies have shown that turmeric can significantly modulate the activity of several drug metabolizing enzymes, this may dramatically affect the bioavailability of several drugs resulting in over dose or less therapeutic effects. This study was directed to evaluate the inhibitory effects of cisplatin and paclitaxel on two CYP450 enzymes namely CYP2E1 and CYP3A1/2 in hepatic microsomes isolated from normal and turmeric pretreated rats. Cisplatin and paclitaxel were added by different concentrations to hepatic microsomes isolated from untreated and turmeric (100 mg/kg/day) pretreated rats for 15 days after receiving pyrazole or dexamethasone for induction of CYP2E1 and CYP3A1/2 respectively. The kinetic potency of these drugs as CYP inhibitors was determined by analysis of Lineweaver-Burk plot. Addition of cisplatin or paclitaxel by (10, 50 and 100 µM) to hepatic microsomes from normal or turmeric pretreated rats caused a concentration dependent inhibition of CYP2E1, with an evidence of less inhibition in turmeric pretreated microsomes particularly at higher concentration. Both drugs at 100 µM displayed a mixed type of inhibition of CYP2E1 in normal or turmeric pretreated microsomes where paclitaxel was the most potent inhibitor. Cisplatin (10, 50 and 100 µM) caused a concentration dependant inhibition of CYP3A1/2 that was enhanced by turmeric pretreatment. The inhibition of CYP3A1/2 by cisplatin (100 µM) was in non-competitive manner with a smaller Ki value in turmeric pretreated microsomes. The inhibitory influence of paclitaxel (10, 50 and 100 µM) on CYP3A1/2 decreased with increasing the drug concentration and this inhibition was augmented by turmeric pretreatment. Interestingly, the inhibition of this enzyme by paclitaxel (10 µM) was switched from mixed type in normal microsomes to competitive manner in turmeric pretreated ones with a marked reduction of Ki values reflecting greater inhibitory influence of paclitaxel on CYP3A1/2 by turmeric pretreatment. In conclusion, turmeric pretreatment attenuated the inhibitory influence of cisplatin and paclitaxel on CYP2E1 activity and magnified their inhibition on CYP3A1/2, thus the use of turmeric with drugs or other medications should raise concern for drugs-herb interactions.

Modulation of age-related changes in oxidative stress markers and energy status in the rat heart and hippocampus: a significant role for ozone therapy.

Oxidative stress emerges as a key player in the ageing process. Controlled ozone administration is known to promote an oxidative preconditioning or adaptation to oxidative stress. The present study investigated whether prophylactic ozone administration could interfere with the age-related changes in the heart and the hippocampus of rats. Four groups of rats, aged about 3 months old, were used. Group 1 (Prophylactic ozone group) received ozone/oxygen mixture by rectal insufflations (0.6 mg/kg) twice/week for the first 3 months, then once/week till the age of 15 months. Group 2 (Oxygen group) received oxygen as vehicle for ozone in a manner similar to group 1. Group 3 (Aged control group) was kept without any treatment until the age of 15 months. A fourth group of rats (Adult control group) was evaluated at 3 months of age to provide baseline data. Ozone alleviated age-associated redox state imbalance as evidenced by reduction of lipid and protein oxidation markers, lessening of lipofuscin deposition, restoration of glutathione levels in both tissues and normalization of glutathione peroxidase activity in the heart tissue. Ozone also mitigated age-associated energy failure in the heart and the hippocampus, improved cardiac cytosolic Ca(2+) homeostasis and restored the attenuated Na(+) , K(+) -ATPase activity in the hippocampus of aged rats. These data provide new evidence concerning the anti-ageing potential of prophylactic ozone administration.

Protective effect of taurine and quercetin against renal dysfunction associated with the combined use of gentamycin and diclofenac.

The potential protective effects of taurine and quercetin against gentamycin (GM)/diclofenac (DC) combined nephrotoxicity were investigated in rats. The results showed that administration of DC alone at an oral dose of 5 mg/kg b.wt/day for 28 days had no significant effect on the measured parameters, except for marked increase in urinary uronic acid excretion. Administration of GM alone at a dose of 100 mg/kg b.wt/day i.p. for 8 days resulted in obvious nephrotoxicity. Combined GM-DC treatment led to the most pronounced nephrotoxicity, as indicated by greater elevations in serum urea, creatinine and urinary N-acetyl-beta-D-glucosaminidase (NAG), together with severe depression of renal cortical Na , K+-ATPase, compared to GM-treated group. Moreover, only combined treatment resulted in significant decrease in urinary potassium and renal cortical glutathione peroxidase (GSHPx), together with an increase in renal cortical lipid peroxidation products (LPOs). Co-administration of taurine or quercetin normalized creatinine clearance and ameliorated the elevations in urinary proteins, uronic acids, NAG and renal cortical LPOs in GM/DC treated rats. The study justifies the use of taurine and quercetin as renoprotective agents against the nephrotoxicity caused by GM/DC therapy.