Effects of saffron extract and crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet

Overweight and obesity are the most common nutritional disorders in the world. The aim of this study was to evaluate anti-obesity effects of ethanolic extracts of saffron and crocin in comparison to orlistat in animal model. Male Sprague Dawley (SD) rats were fed high-fat diet (HFD) for 12 weeks to induce obesity. The saffron extracts (40 and 80 mg/kg), crocin (40 and 80 mg/kg) and orlistat (20 mg/kg) were fed to rats by mixing with high fat diet (HFD) for 8 weeks. Changes in anthropometrical, nutritional and lipid profile parameters were measured. The saffron extract significantly decreased food consumption in obese rats. Crocin (80 mg/kg) showed a significant decrease on rate of body weight gain, total fat pad and weight ratio of epididymal fat to body. Furthermore, crocin (80 mg/kg) significantly reduced plasma levels of triacylglycerol (TG) and total cholesterol (TC) while saffron extract (40 mg/kg) showed major improvement in low-density lipoprotein to high-density lipoprotein (LDL/HDL) level as atherogenic index. These findings demonstrated the potential anti-obesity benefits of saffron extract and crocin in preclinical study

Protective effect of Rheum turkestanicum root against mercuric chloride-induced hepatorenal toxicity in rats

Objective: The present study was designed to investigate the protective effects of hydroalcoholic extract of Rheum turkestanicum against HgCl2 hepatorenal toxicity in rats. Materials and Methods: Animals were randomly divided into five groups (n= 6 in each group) and received HgCl2 and plant’s extract, intraperitoneally. Group1 received saline (1 mL/kg/day), group 2 received extract (200 mg/kg/day), group 3 was treated with HgCl2 (5 mg/kg/day,) and groups 4 and 5 received the extract (100 and 200 mg/kg/day, respectively), 1 hr before HgCl2 administration. All injections last for 3 days. Blood samples and specimens of the liver and kidney were collected 24 hr after the last injection. Results: Data showed that HgCl2 significantly increases liver malondialdehyde (MDA) level, reduces total sulfhydryl content and increases serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, compared to control group. The histopathological changes such as inflammatory cells infiltration was observed in HgCl2-treated group while plant’s extract partially improved histological changes. The extract (100 and 200 mg/kg/day) improved the liver functions as reflected by significant reductions in AST and ALT levels in serum, MDA decreased and the content of total sulfhydryl elevated. Also, the extract improved necrosis and atrophy of the kidney induced byHgCl2. Pretreatment with the extract reduced creatinine and urea in serum, and glucose and protein concentrations in urine, compared to HgCl2- treated group (group III). The extract significantly reversed HgCl2-induced depletion in thiol content and elevation in MDA content. Conclusion: Therefore, oxidative stress may play an important role in HgCl2-induced hepatorenal injury and R. turkestanicum extract may be regarded as a useful to protect the kidney and liver against HgCl2-induced oxidative damage

Reno-protective effect of Rheum turkestanicum against gentamicin-induced nephrotoxicity

Objective(s): Gentamicin belongs to the family of aminoglycoside antibiotics and is a preferred drug in developing countries because of its low cost, availability, and potent effects against bacterial. However, gentamicin can induce nephrotoxicity. In this research, hydroalcoholic extract of Rheum turkestanicum was used against gentamicin- induced nephrotoxicity. Rheum turkestanicum is used against gentamicin-induced nephrotoxicity and in this study its effect against gentamicin-induced nephrotoxicity in rats has been investigated.Materials and Methods: The rats were placed into one of these groups: saline group, gentamicin group that received gentamicin 80 mg/kg/day for six days, and two treatment groups that received R. turkestanicum intraperitoneally at doses of 100 and 200 mg/kg body weight, respectively, 1 hr before gentamicin injections. Urine samples were collected at 24 hr to measure glucose and protein concentration. Blood samples were collected to determine serum urea and creatinine. One kidney was homogenized to measure malondialdehyde and thiol, and the other kidney was kept for pathological studies. Results: Gentamicin increased the level of urinary glucose and protein, and increased malondialdehyde while it decreased thiol in kidney tissue, and increased the concentration of urea and creatinine in the serum. Histopathological pathology revealed renal damage following gentamicin usage; however, the extract was able to improve gentamicin toxicity. Conclusion: R. turkestanicum has positive effects in the attenuation of gentamicin-induced nephrotoxicity

Everolimus, a mammalian target of rapamycin inhibitor, ameliorated streptozotocin-induced learning and memory deficits via neurochemical alterations in male rats

Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. mTOR is a serine/threonine protein kinase and its hyperactivity is involved in the pathophysiology of Alzheimer’s disease (AD) and associated cognitive deficits. The present study evaluated the impact of EVR, on cognitive functions, hippocampal cell loss, and neurochemical parameters in the intracerebroventricular streptozotocin (icv-STZ) model of AD rats. EVR (1 and 5 mg/kg) was administered for 21 days following the single administration of STZ (3 mg/kg, icv) or for 7 days on days 21-28 post-STZ injection after establishment of cognitive dysfunction. Cognitive deficits (passive avoidance and spatial memory), oxidative stress parameters, acetylcholinesterase (AChE) activity, and percentage of cell loss were evaluated in the hippocampus. Chronic administration (1 and 5 mg/kg for 21 days from the day of surgery and icv-STZ infusion) or acute injection (5 mg/kg for 7 days after establishment of cognitive impairment) of EVR significantly attenuated cognitive dysfunction, neuronal loss, oxidative stress and AChE activity in the hippocampus of STZ-AD rats. In conclusion, our study showed that EVR could prevent or improve deteriorations in behavioral, biochemical and histopathological features of the icv-STZ rat model of AD. Therefore, inhibition of the hyperactivated mTOR may be an important therapeutic target for AD

A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with 1 esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661 and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced OS of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5±8.9 months vs. CG+GG: 47.7±5.9 months; p value= 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of ESCC patients. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC. Key word: Esophageal squamous cell carcinoma, risk marker, CDKN2A/B, polymorphis

Hexachlorobutadiene Toxicity in the Young Male Rat.

Hexachlorobutadiene (HCBD), a by-product for the synthesis of perchloroethylene and trichloroethylene and a prominent environmental pollutant, is one of the most nephrotoxic chlorinated hydrocarbons in rodents. Its organ-specific toxicity is based on a bioactivation mechanism that includes hepatic conjugation to produce penta-chlorobutadienyl-glutathione followed by conversion to (penta-chlorobutadienyl)-cysteine and subsequent enzymatic degradation to toxic metabolites by the enzyme GTK/β-lyase. 28-day old male W/A rats received HCBD at 25mg /kg, ip (low dose) or 100mg/kg , ip (high dose). Other groups received probenecid, an organic anion transport inhibitor, (0. 5mmol/kg, 1ml/kg, i. p) before and after HCBD injection. Post mortem light microscopic examination of the kidney showed substantial renal tubular necrosis in HCBD treated rats compare to those which received HCBD plus probenecid and control groups. After 4 to 7 days of exposure, renal tubular damage was decreased, and regeneration in the damaged areas of the kidney was observed. Concentrations of blood urea nitrogen in HCBD treated rats were elevated in the short-term exposure groups. GTK/p-lyase specific activity was lower than control in all the HCBD treated groups. In the HCBD treated groups, apoptotic cell death was demonstrated after 2-3 days using a TUNEL assay and regeneration was demonstrated by immuno-staining for the antigen PCNA.Light microscopic examination of H&E stained brain sections showed extended damage in the choroid plexus of the lateral and third ventricles in rats which had received 100mg /kg dose of HCBD. In groups treated with 25mg /kg of HCBD there was minor damage (minor hemorrhage in the lateral ventricles with pyknotic and mitotic figures in coroidal cells). Brain GTK specific activity in the high dose treated groups was lower than control. Further experiments in which rats were allowed to recover from HCBD treatment before further challenge with HCBD, indicated that the kidney and possibly choroid plexus remained resistant to HCBD toxicity for up to 3 weeks. This period of resistance appeared to coincide with a prolonged reduction of GTK β-lyase activity in these tissues compared to control. The results of this work clearly show that the toxicity of HCBD towards GTK /β-lyase containing cells and subsequent replacement of the damaged cells with cells resistant to HCBD toxicity, is not restricted to the kidney in the young male rat. The choroid plexus of the CNS (a tissue related developmentally to the kidney proximal tubule) is also a target for site-specific toxicity following exposure to HCBD

Hexachlorobutadiene Toxicity in the Young Male Rat.

Hexachlorobutadiene (HCBD), a by-product for the synthesis of perchloroethylene and trichloroethylene and a prominent environmental pollutant, is one of the most nephrotoxic chlorinated hydrocarbons in rodents. Its organ-specific toxicity is based on a bioactivation mechanism that includes hepatic conjugation to produce penta-chlorobutadienyl-glutathione followed by conversion to (penta-chlorobutadienyl)-cysteine and subsequent enzymatic degradation to toxic metabolites by the enzyme GTK/β-lyase. 28-day old male W/A rats received HCBD at 25mg /kg, ip (low dose) or 100mg/kg , ip (high dose). Other groups received probenecid, an organic anion transport inhibitor, (0. 5mmol/kg, 1ml/kg, i. p) before and after HCBD injection. Post mortem light microscopic examination of the kidney showed substantial renal tubular necrosis in HCBD treated rats compare to those which received HCBD plus probenecid and control groups. After 4 to 7 days of exposure, renal tubular damage was decreased, and regeneration in the damaged areas of the kidney was observed. Concentrations of blood urea nitrogen in HCBD treated rats were elevated in the short-term exposure groups. GTK/p-lyase specific activity was lower than control in all the HCBD treated groups. In the HCBD treated groups, apoptotic cell death was demonstrated after 2-3 days using a TUNEL assay and regeneration was demonstrated by immuno-staining for the antigen PCNA.Light microscopic examination of H&E stained brain sections showed extended damage in the choroid plexus of the lateral and third ventricles in rats which had received 100mg /kg dose of HCBD. In groups treated with 25mg /kg of HCBD there was minor damage (minor hemorrhage in the lateral ventricles with pyknotic and mitotic figures in coroidal cells). Brain GTK specific activity in the high dose treated groups was lower than control. Further experiments in which rats were allowed to recover from HCBD treatment before further challenge with HCBD, indicated that the kidney and possibly choroid plexus remained resistant to HCBD toxicity for up to 3 weeks. This period of resistance appeared to coincide with a prolonged reduction of GTK β-lyase activity in these tissues compared to control. The results of this work clearly show that the toxicity of HCBD towards GTK /β-lyase containing cells and subsequent replacement of the damaged cells with cells resistant to HCBD toxicity, is not restricted to the kidney in the young male rat. The choroid plexus of the CNS (a tissue related developmentally to the kidney proximal tubule) is also a target for site-specific toxicity following exposure to HCBD

Protective Effect of Safranal against Gentamicin-Induced Nephrotoxicity in Rat

Gentamicin is an important aminoglycoside antibiotic. Howeverits use is limited to serious and life threatening gram negativeinfections, because of its high nephrotoxicity potential in patients.There are reports that safranal, the active ingredient ofsaffron with antioxidant properties, exerts protective effectagainst ischemic injuries occurred by certain nephrotoxins includinggentamicin. Therefore, in the present study, we examinedthe protective effect of safranal against gentamicin-inducednephrotoxicity in rat. After acclimatization, animals were randomlydivided to three groups (8 rats /each group). On day one,each animal was placed separately in a metabolic cage for collecting24-hour urine samples. On day two, after collectingurine samples for measuring glucose and protein, the rats ingroup 1 received saline 1 ml/kg for 6 days, those in group 2 receivedgentamicin 80 mg/kg/day for 6 days, and the remainingrats in group 3 received safranal 0.5 ml/kg followed by gentamicin80 mg/kg/day for 6 days. Injections were intraperitoneally.All the animals were euthanized 24 hours after the lastdose. Blood samples were collected by cardiac puncture, andconcentration of blood urea, creatinine, and urinary glucose andprotein, as the indicators of nephrotoxicity were measured. Ourresults showed that in group 2, concentration of blood urea nitrogenp<0.01, creatinine p<0.05, urinary glucose p<0.001, andprotein p<0.01 were significantly increased compared with thecontrol and safranal-treated groups. There was no significantdifference between the control and safranal-treated groups.Safranal exerts protective effects against gentamicin-inducednephrotoxicity in rat

Evaluation of Cytotoxicity and Antifertility Effect of Artemisia kopetdaghensis

To date, there is no report on safety of Artemisia Kopetdaghensis. This study aimed to determine the possible undesirable effects of A. Kopetdaghensis on reproduction of female rats. The pregnant rats were treated (i.p.) with vehicle or 200 and 400 mg/kg of A. Kopetdaghensis hydroalcoholic extract from the 2nd to 8th day of pregnancy. Then, number and weight of neonates, duration of pregnancy, and percent of dead fetuses were determined. Also, cytotoxicity of this plant was tested using fibroblast (L929) and ovary (Cho) cell lines. The A. Kopetdaghensis had no significant effect on duration of pregnancy, average number of neonates, and weight of neonates. However, administration of 200 and 400 mg/kg of the extract led to 30 and 44% abortion in animals, respectively. The extract at concentrations ≥200 μg/mL significantly (P<0.001) inhibited the proliferation of L929 fibroblast cells. Regarding the Cho cells, the extract induced toxicity only at concentration of 800 μg/mL (P<0.01). Our results showed that continuous consumption of A. Kopetdaghensis in pregnancy may increase the risk of abortion and also may have toxic effect on some cells

Improved solid phase extraction for selective and efficient quantification of sunset yellow in different food samples using a novel molecularly imprinted polymer reinforced by Fe3O4@UiO-66-NH2

The overuse of synthetic dyes in food products has gradually increased in recent years, resulting food safety and human health has become a global issue. An innovative design of a magnetic molecularly imprinted polymer (Fe3O4@UiO-66-NH2@MIP) for efficient, fast, and selective determination of sunset yellow (SY) from different food products was described in this study. The absorption properties of Fe3O4@UiO-66-NH2@MIP were elucidated by adsorption kinetics, isotherms, reusability, and selectivity experiments. Because of the incorporation of porous Fe3O4@UiO-66-NH2 nanocomposite into molecularly imprinted polymer an efficient nanosorbent with a short equilibrium time, a high adsorption capacity, and a good imprinting factor was finally obtained. The porous Fe3O4@UiO-66-NH2@MIP are also used for quantification of the SY. Under optimal conditions, good linearity (R2 0.9964) in the range of 1.0�120 mg L�1 and a low limit of detection (0.41 mg L�1) was observed with satisfactory recoveries (92.50�106.1) and excellent reusability (RSD � 6.6 after 12 cycles)