Protective effect of nanocurcumin on acetaminophen-induced hepatic and renal toxicities in pigeons.

In this study, the effects of nanocurcumin on acetaminophen-induced acute hepatorenal toxicity in domestic pigeons (Columba livia) were investigated. Fifteen pigeons were randomly assigned into three groups. Group I was served as a negative control group and received tap water as a placebo. Pigeons in groups II and III were administered acetaminophen at the beginning of the experiment (hr 0). Group III was further treated with nanocurcumin, at 12 hr after acetaminophen administration, being continued every 12 hr for two days. The birds were observed for clinical signs of acute drug toxicity. Blood samples were collected from the pigeons at hr 0, 12, 24 and 48 of the experiment for biochemical analysis of the serum. The results showed that acetaminophen toxicity increased the serum levels of aspartate aminotransferase, alanine aminotransferase, urea and uric acid in the pigeons. Nanocurcumin treatment of acetaminophen intoxicated pigeons attenuated increases in biomarkers of the liver and kidney functions towards control levels. Also, the consumption of nanocurcumin minimized histopathological changes in the liver and kidney. A mortality of 60.00% was seen in the acetaminophen-induced toxicity group; while, none of the birds treated with nanocurcumin died. It can be concluded that nanocurcumin alleviates the acetaminophen-induced acute toxic liver and kidney damages, which can lead to pigeon mortality.

Physicochemical and thermal characterization, and evaluation of a bacterial cellulose/Barhang gum-based dressing for wound healing.

The gram-negative bacterium of Gluconacetobacter xylinum is widely used to produce high-quality cellulose in the form of complex strips in microfiber bundles on a commercial scale. In this study, the film-forming potential of bacterial cellulose in combination with polyvinyl alcohol (PVA, 5 % w/v) and Barhang seed gum (BSG, 0.5 % w/v) loaded with summer savory (Satureja hortensis L.) essential oil (SSEO) to prepare a new wound dressing was investigated. The X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), field emission-scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) surface area, in-vitro antibacterial, and in-vivo wound healing activities were performed to assess the structure, morphology, stability, and bioactivity of biocomposite films. Results showed that the SSEO incorporation into the polymeric matrix yielded smooth and transparent composite film with excellent thermal resistance. A significantly robust antibacterial activity against gram-negative bacteria by the bio-film was found. The healing process on mice models revealed that the SSEO-loaded composite film had a promising potential for wound healing associated with improved collagen deposition and reduced inflammatory response.

Protective effects of di- and tri-peptides containing proline, glycine, and leucine on liver enzymology and histopathology of diabetic mice.

CONTEXT: Small peptides as multifunctional biomolecules can prevent the metabolic disorders such as diabetes. OBJECTIVE: The purpose of this study was to investigate the effects of small peptides on the enzymes and histopathology of the liver in mice exposed to diabetes. METHODS: Di- and tri-peptides containing proline, glycine, and leucine were produced by solid phase peptide synthesis (SPPS) protocol. The effects of produced peptides as well as carnosine (Ala-His) and glutathione (Glu-Cys-Gly) were evaluated on hepatic enzymes activity by enzymatic method and histopathology of liver using hematoxylin and eosin and TUNEL staining to assess histologic changes and apoptosis in diabetes induced by multiple low doses of streptozotocin (MLDS). RESULTS: The Ala-His, Leu-Gly and Pro-Gly-Pro peptides had the higher protective effects against the effects of diabetes on the enzymes and histologic changes of liver in mice. CONCLUSION: These peptides can be raised as considerable pharmaceutical preventive agent against diabetes development.

Pro-oxidant and degenerative effects of haloperidol under inflammatory conditions in rat; the involvement of SIRT1 and NF-κB signaling pathways.

The present study was conducted to evaluate the effects of different doses of haloperidol (HP) on induction of oxidative stress in blood and liver cell degeneration in comparison with influences of HP pre-treatment on inflammatory process induced by intraperitoneal (IP) administration of lipopolysaccharide (LPS). One hundred twenty male albino Wistar rats were randomly divided into eight groups (15 in each), including: Control group, LPS group, three groups as HP administration in three divided doses (0.50, 1.00 and 2.00 mg kg-1), and three treatment groups that HP was administered in three doses (0.50, 1.00 and 2.00 mg kg-1) prior to LPS administration. Concentrations of malondialdehyde, activities of antioxidant enzymes including glutathione peroxidase, superoxide dismutase and also the levels of tumor necrosis factor-alpha and interleukin 1-beta were measured in blood and serum. In addition to liver histopathological changes evaluation, hepatic silent information regulator of transcription 1 (SIRT1) and phosphorylated-nuclear factor-κB (p-NF-κB) levels were quantitated. Our findings indicated that sole administration of HP (particularly higher doses) can induce oxidative stress in blood and cell degeneration in liver, while it can attenuate inflammatory process induced by LPS administration presumably via SIRT1 up-regulation and preventing the induction of p-NF-κB. The oxidative and degenerative effects of HP and its impact on inflammatory status were completely dose- dependent according to our results. The possible anti-inflammatory effects of HP may affect reparative mechanisms and hepatic cell degeneration. However, the influences of HP on immune system need further investigations and its higher doses should be administered cautiously especially in patients with immune system dysfunctions.

Betulinic acid reduces the complications of autoimmune diabetes on the body and kidney through effecting on inflammatory cytokines in C57BL/6 mice.

Autoimmune diabetes is one of the most common metabolic diseases with increasing prevalence in the past decades in which pancreatic Langerhans ß cells are destroyed and lead to lack of insulin due to increased blood sugar. One of the consequences of diabetes is glomerular disease of the kidney, also called diabetes nephropathy. Different studies have been carried out on the effects of triterpenoids and their medicinal effects on diabetes mellitus. betulinic acid, a pentacyclic triterpenoid of Terpenes, is found in bushes and trees. Its medical effects are also approved by many studies. In this survey, we studied the effect of betulinic acid on diabetic inbred C57BL/6 male mice. They were randomly divided to three groups. Group A: Consisted of healthy mice which received citrate buffer. Group B: Diabetic mice without any treatment and group C: Treated diabetic mice with betulinic acid. The level of blood insulin level, fasting blood glucose, C-peptide, TNF-α, IFN-γ, and IL-1 cytokines were measured and pathologic studies of the kidney were performed. The results showed that betulinic acid could increase insulin and C-peptide, and decrease fasting blood sugar, kidney lesions and TNF-α, IFN-γ, IL-1 in the treated groups. The differences were significant except for IL-1. Betulinic acid through reduction of inflammatory cytokines could have positive effects on inflammatory and autoimmune disease including autoimmune diabetes.

Troxerutin attenuates inflammatory response in lipopolysaccharide-induced sepsis in mice.

Troxerutin (Tx), known as vitamin P4 is a derivative of natural bioflavonoid rutin. Tx possesses different biological activities such as antioxidant, anticancer, and anti-inflammatory. The current study was conducted to determine potential therapeutic effect of Tx in lipopolysaccharides (LPS)-induced sepsis in mice. In LPS-induced sepsis, the mice were treated intraperitoneally (ip) with Tx twice daily. Therapeutic effect was assessed by measuring serum level of cytokines, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Level of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), Myeloperoxidase (MPO) and Malondialdehyde (MDA) was measured. Expression of CD40 receptor on leucocytes was measured using flowcytometry. Splenocyte proliferation was evaluated using MTT assay. The effect of Tx on survival rate during administration of lethal dose of LPS was investigated. The results showed that Tx inhibited LPS induced NO production. Inflammatory pathways were suppressed by reduction of inflammatory cytokines production. Further, elevated CD40 expression of leucocytes and proliferation of splenocytes markedly reduced in Tx treated group. Antioxidant defense system was enhanced by increased activity of SOD and CAT and decreased level of MDA. MPO, ALT and LDH activity. Additionally, treatment with Tx significantly increased the mean survival time of mice compared with the LPS treated group. Histologically, Tx treatment decreased inflammatory cells infiltration and histopathologicl changes in the liver. Our findings showed that reduced inflammatory parameters, improved antioxidant activity, reduced histological lesions and increased survival rate. These findings suggest that Tx is an effective anti-inflammatory agent for the treatment of LPS-induced sepsis.

Comparison of the effects of hydroalcoholic extract of Capparis spinosa fruit, quercetin and vitamin E on monosodium glutamate-induced toxicity in rats.

Capparis spinosa L. has many biological effects such as antioxidant properties. In the present study, we compared the effects of the hydro-alcoholic extract of Capparis spinosa fruit, quercetin (Q), and vitamin E (Vit E) on monosodium glutamate (MSG)-induced toxicity. The following groups were designed: Control groups (normal saline and/or corn oil); MSG group (4.00 g kg-1 MSG); MSG + low dose extract group (4.00 g kg-1 MSG with 100.00 mg kg-1 extract); MSG + high dose extract (HDE) group (4.00 g kg-1 MSG with 300.00 mg kg-1 extract); MSG + Q group (4.00 g kg-1 MSG with 10.00 mg kg-1 Q); MSG + Vit E group (4.00 g kg-1 MSG with 200.00 mg kg-1 Vit E). All chemicals were orally administered for 14 consecutive days. Tissue specimens from the heart, kidney, and liver tissues and blood samples were collected for histopathological and biochemical evaluations. The results showed that the MSG-induced tissue edema, congestion, and inflammatory cell infiltration were resolved by HDE, Q, and Vit E treatments. These chemicals also restored tissue malondialdehyde level and superoxide dismutase activity. Besides, alterations induced by MSG in serum levels of aspartate transaminase, alanine aminotransferase, urea, lactate dehydrogenase, and creatine kinase-MB were also resolved. It is concluded that Capparis spinosa fruit extract, Q and Vit E can produce approximately similar protective effects on tissue function through oxidative stress alleviation and antioxidant mechanisms restoration.

Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer.

AIMS: Several natural products have been evaluated for management of gastric ulcer induced by non-steroidal anti-inflammatory drugs. Safranal, a plant-derived chemical, has a potent antioxidant and anti-inflammatory properties. The present study was aimed to evaluate possible gastro-protective effects of safranal against indomethacin-induced gastric ulcer in rats. Lansoprazole (a proton pump inhibitor) was used as a reference drug. MATERIALS AND METHODS: Thirty rats were divided into five groups. Groups 1 and 2 received vehicle. Groups 3, 4 and 5 treated with 0.063, 0.25 and 1 mg/kg safranal. Group 6 received 30 mg/kg lansoprazole. All groups except of group 1 received indomethacin (50 mg/kg) ingestion. Six hours later, animals were euthanized and their stomachs were removed. Gastric contents volume and pH were measured. Gastric ulcer area and protective index were evaluated using image J software. Histological changes were evaluated by light microscope. Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) content, tumor necrosis factor-alpha (TNF-α) and Caspase-3 levels were determined in the gastric tissue. KEY FINDINGS: Safranal and lansoprazole normalized gastric volume and pH, reduced gastric ulcer area and produced gastric protection. Indomethacin-induced histological changes and tissue biochemical alterations were ameliorated by the above-mentioned treatments. SIGNIFICANCE: The results of the present study suggest the involvement of anti-secretory, anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms in gastro-protective effect of safranal. In addition, gastro-protective effect of safranal was comparable to lansoprazole.

Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats.

AIMS: Peripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations. MATERIALS AND METHODS: Seventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined. KEY FINDINGS: Carnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values. Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine. SIGNIFICANCE: Carnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery.

Effects of turmeric (Curcuma longa) and vitamin E on histopathological lesions induced in bursa of Fabricius of broiler chicks by salinomycin.

The aim of this study was to evaluate the protective effects of the turmeric in comparison to vitamin E on bursal damages induced by salinomycin in broiler chickens. In this study, forty one day-old broiler chicks were randomly divided into four treatment groups: 1- basal diet as control, 2- basal diet plus salinomycin, 3- basal diet plus salinomycin (SLM) and vitamin E (Vit. E) and 4- basal diet plus salinomycin and turmeric powder. The chicks were treated for two weeks. At the end of the experiment, the bursal tissues were removed and fixed in 10% formalin solution. Tissue sections were stained with hematoxylin and eosin stain for histopathological studies. Light microscopic observations showed that, SLM diminished cortex thickness of bursal tissue, enhanced its medulla zone and caused severe lymphocytic necrosis. In addition, SLM led to fibrosis of interstitium along with sever edema of medulla zone in the bursal tissue of the chicken. Administration of Vit. E and TP significantly inhibited the SLM-induced derangements and comparing the Vit. E and TP showed no significant differences. The results of this study indicated that the turmeric may protect bursa of Fabricius against toxicity induced by salinomycin in chicks.

The role of histamine H1, H2 and H3 receptors of ventral posteromedial nucleus of thalamus in modulation of trigeminal pain.

Histamine receptors are involved in supraspinal modulation of pain. In the present study, we investigated the effects of microinjection of histamine H1, H2 and H3 receptor antagonists and agonists into the ventral posteromedial (VPM) nucleus of the thalamus on two models of trigeminal pain. Right and left sides of VPM were implanted with two guide cannulas. Corneal pain was induced by local corneal surface application of hypertonic saline and the number of eye wipes was recorded. The duration of face rubbing, as an orofacial pain measure, was recorded after subcutaneous (s.c.) injection of capsaicin into the vibrissa pad. 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist, 4µg/site) and dimaprit (a histamine H2 receptor agonist, 1 and 4µg/site) suppressed corneal and orofacial pains. Mepyramine (a histamine H1 receptor antagonist) and ranitidine (a histamine H2 receptor antagonist) at the similar doses of 0.5, 2 and 8µg/site alone had no effects on trigeminal pain. Prior microinjection of mepyramine and ranitidine at a similar dose of 8µg/site inhibited the antinociceptive effects of 2-PEA (4µg/site) and dimaprit (4µg/site), respectively. Immepip (a histamine H3 receptor agonist, 1 and 4µg/site) increased, and thioperamide (a histamine H3 receptor antagonist, 2 and 8µg/site) attenuated nociceptive responses. Prior microinjection of thioperamide (8µg/site) prevented immepip (4µg/site)-induced nociception. These chemicals did not change locomotor behavior. It is concluded that post-synaptic histamine H2, and to a lesser extent H1, receptors and pre-synaptic histamine H3 receptor may be involved in VPM modulation of trigeminal pain.

The effects of crocin, insulin and their co-administration on the heart function and pathology in streptozotocin-induced diabetic rats.

OBJECTIVE: Crocin is a saffron constituent with a potent anti-oxidant activity. The present study investigated the effects of crocin and insulin treatments (alone or in combination) on cardiac function and pathology in diabetic rats. MATERIALS AND METHODS: Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (STZ, 50 mg/kg). Thereafter, crocin (5, 10 and 20 mg/kg, i.p.), subcutaneous (s.c.) injection of insulin (4 IU/kg) and their combination were administered for eight weeks. Blood glucose level and whole heart and body weights were measured. Electrocardiography (ECG) was carried out using the lead II. Serum concentrations of lactate dehydrogenase (LDH), creatine kinase-MB isoenzyme (CK-MB), and the heart tissue malodialdehyde (MDA) and superoxide dismutase (SOD) contents were determined. The heart lesions were evaluated by light microscopy. RESULTS: STZ decreased body weight and increased whole heart weight/body weight ratio. It also decreased heart rate, and increased RR and QT intervals and T wave amplitude. STZ increased blood glucose, serum LDH and CK-MB levels, augmented heart tissue MDA content, decreased SOD content of heart tissue, and produced hemorrhages, degeneration, interstitial edema, and fibroblastic proliferation in the heart tissue. Crocin (10 and 20 mg/kg, i.p.), insulin (4 IU/kg, s.c.) and their combination (5 mg/kg of crocin with 4 IU/kg of insulin) treatments recovered the ECG, biochemical and histopathological changes induced by STZ. CONCLUSION: The results showed cardioprotective effects of crocin and insulin in STZ-induced diabetic rats. The antioxidant and anti-hyperglycemic properties of crocin and insulin may be involved in their cardioprotective actions.

Hydroethanolic Pistacia atlantica hulls extract improved wound healing process; evidence for mast cells infiltration, angiogenesis and RNA stability.

In Iranian traditional therapy folk, the Pistacia is used for treatment of wound inflammation. Here in the present study, the In vivo effect of Pistacia atlantica hulls ointment (PAO) on the wound healing process was assessed. Excision and incision wounds were induced in rats. Three different doses of PAO were administrated. Following 3, 7, 14 and 21 days, the tissue samples were obtained and skin irritation ratio, hydroxyproline content, as well as immune cells, fibroblasts, fibrocytes distribution and collagen density were analyzed. Moreover, the cellular RNA damage examined using epi-fluorescent microscope. Hydroethanolic extract of PAO significantly (P < 0.05) increased wound contraction percentage and up-regulated hydroxyproline content. The animals in medium and high dose PAO-treated groups exhibited remarkably (P < 0.05) higher fibroblast distribution and significantly (P < 0.05) lower immune cells infiltration. PAO up-regulated mast cells distribution on day 7 and elevated neovascularization in a dose dependent manner. Significantly lower RNA damage was revealed in PAO-treated animals. Our data showed that, PAO shortened the inflammation phase by provoking the fibroblast proliferation. Moreover, PAO enhanced mast cells distribution and infiltration, which in turn promoted the neovascularization. Ultimately, promoted angiogenesis increased RNA stability in different cell types. Thus, Hydroethanolic extract of PAO can be considered as an appropriate compound for wound healing medicine.

Protective effects of melatonin and Glycyrrhiza glabra extract on ochratoxin A--induced damages on testes in mature rats.

The effect of Glycyrrhiza glabra extract (GgE) as a natural antioxidant and melatonin (MEL) on ochratoxin A (OTA)-induced histopathological damages on the testes and oxidative stress was evaluated in male rats. The animals were assigned into four groups (n = 8) including control and test groups. The rats in control group received saline and the animals in the test groups received (200 µg/kg) of OTA, (15 mg/kg) of MEL + (200 µg/kg) OTA and (100 mg/kg) of GgE + (200 µg/kg) OTA, respectively, during 28 consecutive days. The serum total antioxidant power (TAOP) and total thiol molecules (TTM) production were assessed. Moreover, histopathological and histochemical studies were also performed. The results showed that the TAOP and TTM were decreased in OTA-exposed rats, while the animals that received MEL + OTA or GgE + OTA showed an enhancement in the serum TAOP and TTM levels. Histopathological analyses demonstrated that in OTA-exposed rats, the testicular degeneration, seminiferous tubule atrophy, dissociation of germinative epithelium, vasodilatation with vascular thrombosis, perivascular immune cell infiltration, hypertrophied leydic cells, giant cell formation, and negative tubular differentiation index (TDI) were observed. Surprisingly, both the biochemical and histopathological examinations showed that MEL and GgE, albeit with some differences, exerted a protective effect on OTA-induced damages. In conclusion, this data suggest that OTA contamination in animal feeds and human foods could cause reproductive abnormalities. Our data also indicate that OTA, at least partly by interfering in oxidative stress system, exerts its toxic effects on testes whereas MEL and GgE with antioxidant properties could fairly protect rats against OTA toxic effects.