Objective: Lead poisoning is one of the oldest occupational and environmental diseases in the world. It can enter the body by being absorbed in water, air, and food. Oxidative stress is one of the mechanisms responsible for lead toxicity. Anti-inflammatory and antioxidant properties are the primary effects of pomegranate seed oil (PSO). This research is designed to determine the impact of PSO on damage to the hippocampus, bone, and bone marrow in rats triggered by lead acetate. Materials and Methods: Thirty-two adult male rats were subjected to this study. The animals were divided into four groups at random after they had acclimated. The control group received 1 ml/kg of normal saline for 21 days. Animals in the Pb group received 500 ppm of lead acetate in drinking water for 21 days. Pb+ PSO 0.4 ml/kg and Pb+ PSO 0.8 ml/kg received 0.4 or 0.8 ml/kg of PSO intraperitoneally, concomitant with exposure to lead acetate for 21 days. Blood, bone, bone marrow, and hippocampus samples were taken after the treatment for measuring malondialdehyde (MDA), thiol content and superoxide dismutase (SOD). Results: Our results revealed that 0.8 ml/kg of PSO significantly decreased malondialdehyde in bone marrow, serum, and hippocampus. It also could increase thiol in serum and superoxide dismutase in bone marrow. Conclusion: PSO could protect against lead-induced damage in bone, bone marrow, and hippocampus of treated animals through reduction of oxidative stress.

During recent decades, the application of zirconium dioxide nanoparticles (ZrO 2 -NP) has been expanded in various fields ranging from medicine to industry. It has been shown that ZrO 2 -NP has the potential to cross the blood–brain barrier (BBB) and induce neurotoxicity. In the current study, we investigated the in vivo neurotoxicity, as well as, the cellular mechanism of ZrO 2 -NP toxicity on two neuronal-like cell lines, PC12 and N2a. PC12 and N2a cells were exposed to increasing concentrations of ZrO 2 -NP (0-2000 µg/ml) for 48 h. The apoptotic effect of ZrO 2 -NP was determined using annexin V/propidium iodide double staining (by flow cytometry), and western blot analysis of relative apoptotic proteins, including caspase-3, caspase-9, bax, and bcl2. Based on our results, ZrO 2 -NP at concentrations of 250-2000 μg/mL increased both early and late-stage apoptosis in a concentration-dependent manner. Moreover, the expressions of cleaved-caspase-3 and -9 proteins and the bax/bcl2 ratio were significantly increased. In addition, oral administration of ZrO 2 -NP (50 mg/kg) to male Wistar rats for 28 days led to the loss of neuronal cells in the cerebral cortex. Taken together, our findings highlighted the role of apoptosis on cytotoxicity induced by ZrO 2 -NP.

Background & Objective: Aging is a natural phenomenon which can cause changes in most organs and cells.Numerous mechanisms including oxidative stress and free radical generation is involved in the progression of the aging process.Pomegranate seed oil (PSO), has different therapeutic properties including antioxidant and anti-inflammatory effects.In this research, the effect of PSO against Dgalactose-induced aging is investigated.Materials & Methods: D-galactose, 500 mg/kg, injected subcutaneously (S.C.) to induce aging in rats.Animals in treatment groups received PSO, 0.4 and 0.8 ml/kg intraperitoneally (i.p.).After 42 days, behavioral test was evaluated by passive avoidance (PA).Then animals killed, blood samples collected by cardiac puncture, and brain and liver removed.Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) measured in serum.Malondialdehyde (MDA) and thiol contents of brain and liver homogenized tissue samples were determined.Results: D-galactose increased lipid-peroxidation in liver and brain tissues as well as elevation of ALT, AST, but the level of thiol contents decreased in homogenized tissues.Both doses of PSO attenuated d-galactose-induced injury in liver and brain by decreasing ALT, AST, MDA and elevation of thiol content.The PA test showed that PSO increased the latency time to enter the dark chamber compared to the control group. Conclusion:PSO decreased D-galactose-induced aging in rats via prevention of oxidative stress.This effect may be related to the presence of various compounds and their anti-oxidant properties, which is found in PSO.

Background: Inflammation plays a major part in brain ischemia. Propolis is a polyphenol-rich hive product with a set of pharmaceutical properties. Objectives: This research aims to investigate the impact of water extracts of brown propolis (WEPs) on stroke outcomes and inflammatory responses in a rat model of permanent middle cerebral artery occlusion (MCAO). Materials & Methods: This experimental study was conducted in Rafsanjan, Iran, in 2017. WEPs were experimentally prepared from two regions in Iran. Gas chromatography–mass spectrometry and Folin–Ciocalteu assays were used to determine chemical portrayal and the total polyphenol content, respectively. A total of 66 male adult mice were divided randomly into the surgical sham, control (vehicle-treated), and four WEPs-treated animal groups. WEPs-treated groups received doses of 100 and 200 (mg/kg, IP) four times, and their behavioral tests, brain edema, infarct volume, and tumor necrosis factor-alpha (TNF-α) level were evaluated. Results: The samples were not significantly different in terms of the concentration of the total polyphenol content. Compared to the control, WEPs led to a substantial decrease in the TNF-α level (P<0.05) as well as a subsequent reduction in the brain edema and infarct volume (P<0.001) in all treatment groups. Furthermore, there was a significant improvement in neurological deficits and sensory-motor impairments level (P<0.05). Conclusion: According to the study findings, WEPs reduce brain ischemia damage, perhaps by exerting a neuroprotective effect on stroke-induced neuroinflammatory responses

Objective: The clinical use of tacrolimus is limited due to its side effects. This research investigated the protective activities of pomegranate seed oil (PSO) against TAC toxicity. Materials and Methods: The groups are included normal (1 ml of corn oil), TAC (2 mg/kg), and co-treatment of PSO (0.4 and 0.8 ml/kg) and TAC. All administrations were carried out intraperitoneally for 14 days. After the last injection, blood was collected from the heart. Results: TAC increased creatinine and urea. Increased malondialdehyde, reduced thiol content and superoxide dismutase. The elevation of lactate dehydrogenase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase-MB and creatinine phosphokinase that confirmed cardiac toxicity. PSO reduced TAC toxicity. PSO decreased TAC-induced pathology injury. Conclusion: PSO reduced TAC toxicity in renal and heart via scavenging free radicals.

The sudden increase of the COVID-19 outbreak and its continued growth with mutations in various forms has created a global health crisis as well as devastating social and economic effects over the past two years. In this study, a screen-printed carbon electrode reinforced with boron nitride quantum dots/flower-like gold nano structures (BNQDs/FGNs/SPCE) and functionalized by highly specific antisense DNA oligonucleotide presents an alternative and promising solution for targeting SARS-CoV-2 RNA without nucleic acid amplification. The platform was tested on 120 SARS-CoV-2 RNA isolated from real clinical samples (60 positive and 60 negative confirmed by conventional RT-PCR method). Based on obtained quantitative results and statistical analysis (box diagram, cutoff value, receiver operating characteristic curve, and t-test), the biosensor revealed a significant difference between the two positive and negative groups with 100% sensitivity and 100% specificity. To evaluate the quantitation capacity and detection limit of the biosensor for clinical trials, the detection performance of the biosensor for continuously diluted RNA isolated from SARS-CoV-2-confirmed patients was compared to those obtained by RT-PCR, demonstrating that the detection limit of the biosensor is lower than or comparable to that of RT-PCR. The ssDNA/BNQDs/FGNs/SPCE showed negligible cross-reactivity with RNA fragments isolated from Influenza A (IAV) clinical samples and also remained stable for up to 14 days. In conclusion, the fabricated biosensor may serve as a promising tool for point-of-care applications.

A novel and reliable electrochemical analysis tool was developed for gemcitabine (GEM) detection by combining the selective recognition of molecular imprinted polymer (MIP) technology and ratiometric quantification strategy. In this contribution, a glassy carbon electrode (GCE) surface was first modified by drop-coating CuCo2O4/NCNTs and ferrocene (FC) to achieve a ratiometric on-off response (CuCo2O4/NCNTs/FC was served as a substrate to amplify signal and to provide reference signal). Then, MIP network was prepared through in situ electrochemical polymerization, using aniline as monomer and GEM as template. Differential pulse voltammetry (DPV) analysis showed that the oxidation peak signal of FC decreased with the increase of GEM concentration, whereas the oxidation peak signal of GEM increased. Therefore, the peak current ratio of IGEM/IFC was employed to accurately reflect the concentration of GEM. Using this method, GEM was measured in the range from 0.1 to 150 mu M with a low limit of detection of 11.3 nM. In addition, the sensor showed high reproducibility, anti -interference ability and good stability for 6 weeks toward GEM detection. Finally, the proposed sensor exhibi-ted excellent detection performance in complex pharmaceutical and biological matrices with satisfactory recoveries.

Aging promotes damage to vulnerable organs like brain and liver. Sanguisorba minor has been traditionally used to cure various ailments. Few studies have reported pharmacological activities of this medicinal plant. This research aimed to investigate the effects of Sanguisorba minor extract (SME) on brain and liver injury in aging rats and identify the underlying mechanisms. The aging model was developed by subcutaneously injecting D‑galactose and simultaneously treating them with SME. After biochemical and pathological assessments, mRNA expression levels of nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2) and Nrf2‑ regulated gene, heme oxygenase‑1 (HO‑1), in the brain and liver tissues were determined. As a result, malondialdehyde and acetylcholinesterase levels were elevated while total thiol content and superoxide dismutase were reduced in the aging rats. Treatment with the extract remarkably attenuated oxidative injury and pathological changes in liver and brain tissues. Concomitantly, the extract up‑regulated Nrf2 and HO‑1 genes. Our findings exhibited SME may improve the aging‑related brain and liver damage through the Nrf2‑HO‑1 pathway.

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).

3-Acetyl- 11-keto-beta- boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 mu M) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P <.001). However, AKBA (2.5-10 mu M) enhanced the cell viability in both treatment regimens (P <.001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P <.05 and P <.001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P <.001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate- induced programmed cell death through depressing the elevation of the expression ratio of Bax/ Bcl-2 and cleaved-caspase-3 proteins, concentration- dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate- induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.

Safranal, isolated from saffron (Crocus sativus L.), is known to possesses neuroprotective effects. In this study, the neuroprotective potential of safranal against PC12 cell injury triggered by ischemia/reperfusion was investigated. PC12 cells were pretreated with safranal at concentration ranges of 10–160 μM for 2 h and then deprived from oxygen-glucose-serum for 6 h, followed by reoxygenation for 24 h (OGD condition). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2,7-dichlorofluorescin diacetate (DCF-DA), and comet assays were used to measure the extent of cellular viability, reactive oxygen substances (ROS), and DNA damage, respectively. Also, propidium iodide (PI) flow cytometry assay and western blotting of bax, bcl-2, and cleaved caspase-3 were performed for assessment of apoptosis. OGD exposure reduced the cell viability and increased intracellular ROS production, oxidative DNA damage, and apoptosis, in comparison with untreated control cells. Pretreatment with safranal (40 and 160 μM) significantly attenuated OGD-induced PC12 cell death, oxidative damage, and apoptosis. Furthermore, safranal markedly reduced the overexpression of bax/bcl-2 ratio and active caspase-3 following OGD (p < 0.05). The present findings indicated that safranal protects against OGD-induced neurotoxicity via modulating of oxidative and apoptotic responses. Graphical abstract

Background and purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Excessive proliferation of fibroblast-like synoviocytes (FLS) and over-expression of angiogenic factors play a crucial role in pannus formation and joint destruction in RA. Clarification of the role of cholinergic agonists in modulation of inflammation and immune system reactions is progressively ongoing. In this study, the anti-angiogenic effect of two cholinergic agonists, nicotine and ARR17779, on human FLS, and monocytic cell lines (U937) was evaluated.Experimental approach: The cells were cultured in DMEM supplemented with 10% FBS and treated with different doses of nicotine and ARR17779 in the presence of TNF-α, LPS, and IFN-γ. After 48 h, cell number was counted in different groups. After RNA extraction, cDNA was synthesized and the expression of VEGF and MMPs has been evaluated by real-time PCR using specific primers and probes. VEGF was assayed in U937 cell line supernatant using ELISA method.Key results: Both nicotine and ARR17779 inhibited FLS and U937 cell proliferation. Cholinergic agonists reduced the expression of MMPs and VEGF. VEGF level in supernatant of U937 cells treated with cholinergic agonists was also reduced.Conclusion and implications: Our results suggest that cholinergic agonists can modulate pathological conditions related to pannus formation in in-vitro conditions. Based on these results, cholinergic agonists can be considered as novel therapeutic options in RA. Further animal studies are needed before introducing these agents into clinical uses.

Introduction: Stroke is one of the leading causes of death and disability worldwide. Propolis, a polyphenol-rich resinous product processed by honeybees from a variety of plant sources, has a set of biological activities. We investigated the neuroprotective effect of Iranian brown propolis (IBP) in a mouse model of permanent middle cerebral artery occlusion (MCAO). Methods: Experimentally, water extracts of propolis (WEPs) were obtained from Kerman (KeWEP) and Khorasan Razavi (KhWEP) provinces, Iran. The chemical characterization and total polyphenol content of WEPs were determined using the Folin–Ciocalteu assay and gas chromatography-mass spectrometry (GC-MS). Animals were divided into eight experimental groups including: sham, control, and three groups each of which KeWEP- and KhWEP-treated mice. The drugs were administered at doses of 30, 100 and 200 mg/kg, intraperitoneally (IP), during four different time points. Infarct volume and brain edema were measured at 48 h. Behavioral tests were evaluated at 4, 24 and 48-hour post stroke. Results: The total polyphenol content was 1100 and 1400 mg/L in KhWEP and KeWEP respectively. Compared to the control group, the doses of 100 and 200 mg/kg in both samples decreased infarct volume. Brain edema was also reduced in all treatment groups. The dose of 200 mg/kg in both samples and 100 mg/kg in the KeWEP-treated group significantly increased grasping ability. Sensory-motor function was improved in all groups, too. Conclusion: These results suggest that IBP may reduce ischemic brain injury by its neuroprotective effect on focal cerebral ischemia.

3-Acetyl-11-keto-β-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata , has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a ( P  < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens ( P  < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury ( P  < .05 and P  < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen ( P  < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.

This study introduces an innovative procedure for the development of a molecularly imprinted electrochemical sensor for ultra-sensitive and selective detection of patulin. Firstly, the surface of a glassy carbon electrode (GCE) was decorated by nitrogen doped graphene quantum dots (N-GQDs) and AuNPs-functionalized Cu-metal organic framework (Au@Cu-MOF) and then a layer of molecularly imprinted polymer (MIP) was grown on Au@Cu-MOF/N-GQDs/GCE by electropolymerization. Electrochemical techniques were used to characterize and study the electrochemical behavior of the MIP/Au@Cu-MOF/N-GQDs/GCE, which exhibited a stable reference peak of Au@Cu-MOF at -0.11 V after elution of patulin molecules. This peak current density decreased with rebinding of patulin molecules therefore it was considered as indicator signal. The designed MIP sensor presented a wide linear range from 0.001 to 70.0 ng mL(-1), and a low detection limit (0.0007 ng mL(-1)). This newly developed method based on the synergistic effects of N-GQDs and Au@Cu-MOF combined with MIP technique offered outstanding selectivity, sensitivity, stability, and reproducibility. The good accuracy (recovery%, 97.6-99.4) and high precision (RSD%, 1.23-4.61) of this sensing system for analysis of apple juices proved the high potential of it for rapid and low cost determination of patulin compared to chromatographic methods.

Hexachlorobutadien is nephrotoxic agent in rodents. The mechanism of toxicity includes generation of free radicals, depletion of thiol groups and production of toxic metabolites. Antioxidant compounds may reduce HCBD-nephrotoxicity. In this research we investigated the effect of Rheum turkeatanicum extract against HCBD-toxicity. The animals were divided to 4 groups which were including control (saline, 1 mL/kg), HCBD (100 mg/kg) and treatment groups which received extract at doses 100 and 200 mg/kg. The extract were administered as intraperitoneally (i.p.) 1 h before HCBD injection (i.p.). The animals were anesthetized by ether, 24 h after HCBD administration. The results showed elevation of serum creatinine, serum urea, urinary protein, urinary glucose, malondialdehyde levels in kidney and reduction of thiol in kidney by HCBD. The histopathological studies showed that there was apoptosis and necrosis in HCBD treated groups. Administration of R.turkestanicum reduced HCBD toxicity. The extract reduced hitopathological changes in kidney. It may be concluded that the nephroprotective effect of extract may be due to different mechanisms such as antioxidant activity or by decreasing the toxic metabolites of HCBD or inhibition of enzymes which are involved in the bioactivation of HCBD such as glutathione-S-transferase (GST) or cysteine-S-conjugate beta-lyase.

Objectives 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 and 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.

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.

Background: Cisplatin is used as chemotherapeutic drug in the treatment of some solid tumors. It causes different side effects such as nephrotoxicity because of increasing oxidative stress and reactive oxygen species production. This study was designed to investigate the effect of Rheum turkestanicum on cisplatin-induced nephrotoxicity in rat. Materials and Methods: Animals were randomly divided into four groups (six each). Group I received normal saline (1mL/day, intraperitoneally [i.p.]). Group II received a single dose of cisplatin (8mg/kg, i.p.). Groups III and IV received extract at doses of 100mg/kg and 200mg/kg, i.p., respectively, for 3 consecutive days, 1h before a single dose of cisplatin only at the first day. Blood samples were taken for measuring the level of urea and creatinine. Furthermore, 24-h urinary factors such as glucose and protein were measured. Histopathological observation was carried out on kidney sections. Statistical analysis was performed using one-way analysis of variance followed by Tukey–Kramer post hoc test for multiple comparisons. Results: Cisplatin increased the lipid peroxidation, serum creatinine, serum urea, urinary glucose, and urinary protein, whereas decreased the content of thiol in kidney. The extract reduced serum creatinine, serum urea, urinary glucose, urinary protein, lipid peroxidation, and increased thiol following cisplatin administration. Histological studies revealed lower lesions in kidney in the extract-treated groups compared to cisplatin-treated one. Conclusion: This research showed the extract has protective effect against cisplatin-induced nephrotoxicity. This observation may be related to antioxidant properties of the extract.

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.