Role of innate immunity and oxidative stress in steroid-induced cataracts in developing chick embryos

Purpose: The exact etiopathogenesis of steroid-induced cataracts (SIC) is not known. Although oxidative stress is one of the most acceptable hypotheses, the exact molecular events in steroid-induced oxidative events in the lens need to be clarified. In addition, to the best of our knowledge, the innate immune system components in SIC formation have not been studied previously. The aim of the present study was to study the oxidative system and the innate immune system components in the cataractous lenses of a developing chick embryo SIC model.

Materials and methods: The study included 20 specific pathogen-free (SPF) fertilized eggs divided into two groups, with one hydrocortisone (HC)-treated group (G1) and one non-HC-treated control group (G2). On the 15th day of incubation, the SPF eggs in the two groups were removed from the incubator; HC was injected into G1, and phosphate-buffered saline (PBS) was injected into G2 using insulin injectors into the chorioallantoic membrane. On day 17, all of the chick embryos were removed from the eggs, and all lens and liver tissues were dissected from the embryos. Cataract formation was evaluated in all lenses, and total antioxidant status (TAS), total oxidant status (TOS), reduced glutathione (GSH), oxidized glutathione (GSSG), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels were measured in all lens and liver tissues.

Results: The lenses in the SIC group had lower levels of GSH, GSSG, TAS, and IL-6 (p?=?0.016, 0.022, 0.000, 0.000, respectively), and higher levels of TOS (p?=?0.000) than the control group. Furthermore, the liver tissues in the SIC group had decreased levels of TAS and IL-6, and increased levels of TOS compared to the control tissues (p?=?0.000). Although the IL-1β levels in the lens and liver tissues in the HC-induced cataract group were lower than in the control group, these differences were not statistically significant. In addition, the GSH levels in the liver tissues did not statistically differ between the two groups despite the significant GSH difference in the lens tissues.

Conclusions: Steroid therapy causes a decrease in GSH, GSSG, and TAS levels and an increase in TOS levels in lens tissues, which means there is increased oxidative stress and decreased antioxidant defence. Furthermore, lenses with SIC have lower IL-6 levels compared to non-cataractous lenses. The interaction between lenticular IL-6 and antioxidant defence needs to be further studied.     

Effects of Pycnogenol on cisplatin-induced optic nerve injury: an experimental study

Aim: To determine the effects of Pycnogenol on cisplatin-induced optic nerve damage.

Material and method: Totally 18 albino Wistar male rats were assigned into three groups, with six rats in each group as follows: healthy controls (HC group), only cisplatin (2.5?mg/kg) administered group (CIS group) and Pycnogenol (40?mg/kg)?+?cisplatin (2.5?mg/kg) administered group (PYC group). We analyzed the levels of malondialdehyde (MDA) as a marker of lipid peroxidation and oxidative stress, total glutathione (tGSH) as a marker of antioxidant status, nuclear factor-kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) as inflammatory markers, total oxidative status (TOS) and total antioxidant status (TAS) on eye tissue together with histopathological evaluation of optic nerve in an experimental model.

Results: In CIS group MDA, TOS, TNF-α and NF-κB levels were statistically significantly higher (p?p?p?p?Conclusion: Pycnogenol pretreatment was highly effective in preventing augmentation of cisplatin-induced oxidative stress and inflammation in eye tissue.     

The effects of lycopene on alloxan induced diabetic optic neuropathy

Aim: To determine the effects of lycopene treatment in prevention of diabetes associated inflammatory response and oxidative stress in an experimental model. With this aim we investigated the levels of oxidative stress markers including Malondialdehyde (MDA), and total oxidative status (TOS)together with inflammatory markers including nuclear factor- kappa B (NFKB) and tumor necrosis factor α (TNF-α) and antioxidants including total glutathione (TGSH), total oxidative status (TOS) and total anti-oxidative status (TAS) levels on eye tissue.

Material and methods: Totally 18 albino Wistar male rats (250–280 grams) assigned into three groups, with six rats in each group as follows: healthy group (HG), control group (CG), and lycopene group (LG). The diabetes was induced with alloxan administration in rats of CG and LG. Lycopene (4?mg/kg) was administered to the rats in LG once a day for 3?months. At the end of this period, the animals were sacrificed and their eyes were enucleated for histopathological evaluations. From the tissues, MDA, GSH, TOS, TAS, TNF-α and NF-κB levels were analyzed.

Results: MDA, TOS, OSI, NFKB and TNF-α levels were significantly higher, while TGSH and TAS levels were significantly lower in CG compared with HG (p?p?Conclusion: For the first time in literature we determined that, lycopene was significantly effective in prevention of augmented inflammation and oxidative stress on eye tissue associated with diabetes, as well as the tissue damage on optic nerve. However, studies investigating the long-term clinical effects of lycopene on diabetic individuals are warranted.     

Effect of bisphenol A on blood glucose,lipid profile and oxidative stress indices in adult male mice

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical, has been considered as a possible risk factor for diabetes and its complications. However, the underlying mechanisms of BPA-induced diabetes are not clear. The present study was performed to evaluate the effects of BPA on the hyperglycemia, lipid abnormalities and oxidative stress. In this study, the mice were divided into three groups of six animals each: One group as a control (C) and two other groups which exposed to 0.5 and 2?mg/kg concentrations of BPA. BPA powder was dissolved in sterile extra virgin olive oil and injected intraperitoneally to the tested groups, while the control group only received pure olive oil for 4 weeks. After 4 weeks, the changes of glucose, lipid profile reduced, total protein, glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), catalase (CAT) and super oxide dismutase (SOD) were determined in serum and pancreas. The results indicated that BPA dose-dependently increased the levels of blood glucose, lipid profile and MDA in the tested groups compared with the control group (p?<?0.001). BPA reduced significantly the levels of HDL-C and GSH in dose-dependent manner (p?<?0.001). BPA injection increased the levels of MDA and decreased the levels of GSH and TAS, and also the activities of SOD and CAT in the pancreas of exposed mice compared with the control group (p?<?0.05). In addition, body weight increased in the mice exposed to BPA compare to control animals. These results suggest that BPA exposure might induce hyperglycemia and its complications in adult male mice by induction of oxidative stress.     

Antioxidant effects of vitamin D on lacrimal glands against high dose radioiodine-associated damage in an animal model

Purpose: To evaluate antioxidant effects of active vitamin D (calcitriol) against high-dose radioiodine (RAI) therapy-associated damage of lacrimal gland.

Materials and methods: Wistar albino rats were used and divided into three groups randomly (n?=?12/group). The first group was appointed as the negative control group and received no RAI or medication. The second group was appointed as the positive control group that only received 3?mCi/kg (111 MBq/kg) RAI via gastric gavage and the last group was the treatment group that received 3?mCi/kg RAI via same method and calcitriol (200?ng/kg/day) via intraperitoneal administration. Seven days after RAI administration, bilateral intraorbital (IG), extraorbital (EG) and Harderian (HG) glands were removed for the evaluations of histopathologic, tissue cytokine, total oxidant status (TOS) and total antioxidant status (TAS).

Results: RAI led to significant increase in tissue TOS, TNF-α, IL-6 levels and significant decrease in IL-10 and TAS levels (p?p?p?p?=?0.049), periductal fibrosis in EG and HG (p?=?0.049 and 0.038, respectively), abnormal cell outlines in EG and HG (p?=?0.020 and 0.011, respectively) and variation in cell size in the IG and the HG (p?=?0.003 and 0.049 respectively).

Conclusions: RAI caused significant oxidative stress and inflammation in lacrimal glands. Vitamin D demonstrated potent anti-inflammatory, antioxidant and radio-protective effects on lacrimal glands in histopathologic, tissue cytokine and oxidant/antioxidant level evaluations.     

Protective effects of N-acetylcysteine on triamcinolone acetonide-induced lens damage in rats

Objective: To examine the relationship of cataract forming effect of intravitreal triamcinolone acetonide (IVTA) injection with oxidative status and the effect of N-acetylcysteine (NAC) on these alterations.

Materials and methods: Twenty-six Wistar-Albino rats were included in the study. Rats were assigned into four groups as follows: intravitreal saline injection group (controls); IVTA injection group; IVTA?+?intraperitoneal NAC injection group (IVTA?+?NAC); and intraperitoneal NAC injection group (NAC). Triamcinolone acetonide was intravitreally injected at a dose of 1?mg. NAC was intraperitoneally injected at a dose of 150?µg/g body weight. Animals were sacrificed and lens specimens were analyzed for levels of malondialdehyde (MDA) and protein carbonyl (PC) and activities of glutathione (GSH) and glutathione peroxidase (GSH-Px).

Results: We found that the MDA and PC levels of lenses were increased in the IVTA group (p?p?p?Conclusion: These results indicate that the NAC produces a protective mechanism against IVTA-induced cataract and suggest a role of oxidative stress in pathogenesis.     

Neuroprotective effects of alkaloids from Piper longum in a MPTP-induced mouse model of Parkinson’s disease

Abstract

Context: Alkaloids of Piper longum L. (Piperaceae) (PLA) include piperine and piperlonguminine. Piper longum and piperine have multiple biological properties including antioxidant activity.

Objective: The present study investigated the neuroprotective effects of PLA in a MPTP-induced mouse model of Parkinson’s disease.

Materials and methods: PLA was prepared by extracting the dry seed of P. longum using 85% ethanol. Adult male C57BL/6 mice were divided into eight groups of 12 rats each. Experimental and control groups received an equivalent volume of saline, 0.5% CMC-Na, and 0.1% Tween 80, treated groups received oral PLA (30, 60, and 120?mg/kg), other groups treated with piperine (60?mg/kg) or Madopar (50?mg/kg). The PLA prevention group (PLA-Pr) administrated PLA (120?mg/kg) for 1 week before MPTP challenged. Except for the PLA-Pr group, others were treated for seven consecutive weeks. Parkinson’s disease was induced by injecting MPTP intraperitoneally (25?mg/kg) twice weekly for five consecutive weeks. Dopaminerigic (DA) neurons and their metabolism were detected by UFLC-MS/MS. Tyrosine hydroxylase (TH)-immunohistochemistry assay and Western blotting were performed. The antioxidant enzymatic levels were determined by kit-based assays.

Results: The LD₅₀ value of PLA was determined at 1509?mg/kg of body weight. PLA (60?mg/kg) can significantly increase total movement time and distance (p?<?0.05), increase levels of DA (p?<?0.05) and DOPAC (p?<?0.05), increase glutathione (GSH) level and superoxide dismutase (SOD) activity (p?<?0.05), and decrease the lipid peroxidation of malondiadehycle (MDA) (p?<?0.05) in PLA-treated groups as compared with the control group.

Discussion and conclusion: Our results indicate that PLA possesses neuroprotective effects and has ameliorative properties in dopaminergic neurons.     

Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes

Context: Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia.

Objective: The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ)?+?nicotinamide-induced diabetes.

Materials and methods: Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ?+?nicotinamide-induced diabetes that received a single dose of STZ (65?mg/kg) and nicotinamide (110?mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2?g/kg/d, gavage), and normal rats that received garlic (2?g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats.

Results: The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p?p?p?p?p?Discussion and conclusion: These results indicate that garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.     

The effects of lutein on cisplatin-induced retinal injury: an experimental study

Aim: Lutein is one of the most common carotenoids defined in human plasma as having potent anti-oxidant effects. We aimed to determine the biochemical and histopathological effects of lutein on cisplatin-induced oxidative retinal injury in rats.

Materials and methods: Twenty-four rats were equally divided into four groups as healthy controls (HC group), only cisplatin (5?mg/kg) administered group (CIS group), Lutein (0.5?mg/kg)?+?cisplatin (5?mg/kg) administered group (LC group), and only Lutein (0.5?mg/kg) (LUT group) administered group. From the blood samples obtained, serum malondialdehyde (MDA), total glutathione (tGSH), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were investigated. In histopathological analyses, the total retinal thickness, retinal pigment epithelium (RPE), photoreceptor layer (PL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL) were evaluated.

Results: MDA, IL-1β, and TNF-a levels were statistically significantly higher (p?p?Conclusions: Lutein co-administration was highly effective in prevention of cisplatin-induced retinal damage due to the anti-oxidant and anti-inflammatory effects of lutein.     

The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice

Context: Acetaminophen overdose is regarded to a common cause of acute liver failure. The hepatotoxicity leads to mitochondrial oxidative stress and subsequent necrotic hepatocellular death.

Objective: This study examines the protective effect of metformin on acetaminophen-induced oxidative stress, inflammation and subsequent hepatotoxicity in mice.

Materials and methods: Male BALB/c mice were orally administered to acetaminophen (250?mg/kg/d) for a 7-day period. The mice received metformin (100 and 200?mg/kg/d, p.o.) for 21 days. To evaluate acetaminophen-induced oxidative stress, liver tissue level of malodialdehyde (MDA), end product of membrane lipid peroxidation, and activities of superoxide dismutase (SOD) and glutathione (GSH) were measured. Histological analysis and measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were performed. Moreover, tissue concentrations of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), along with, C-reactive protein (CRP) were assessed.

Results: Acetaminophen caused focal hepatocyte necrosis, inflammation and fatty degeneration, as well as increased tissue levels of AST, ALT, ALP and MDA, and also decreased GSH and SOD activities. Moreover, IL-6, TNF-α and CRP levels were increased following acetaminophen hepatotoxicity. Metformin (200?mg/kg/d) significantly normalized MDA, SOD and GSH levels (p?<?0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p?<?0.001). The tissue levels of IL-6, TNF-α and CRP were markedly decreased by 21-day treatment with metformin (200?mg/kg/d) (p?<?0.001).

Discussion: The results suggest metformin protects hepatocytes against acute acetaminophen toxicity. Metformin is indicated to diminish oxidative stress, proinflammatory cytokines, and hepatocyte necrosis.     

Does moxifloxacin alter oxidant status in the cornea? An experimental study

Objective: In this experimental study, we investigated the possible effects of intracameral moxifloxacin on oxidative stress parameters and endothelial cell morphology in corneal tissue.

Methods: In total, 30 rats were randomly assigned to three groups of 10 rats: the sham group (Group 1, n?=?10); the control group (Group 2), where balanced salt solution (BSS) was administered at a dose of 0.01?cc (n?=?10); and the treatment group (Group 3), where moxifloxacin was administered at a dose of 0.05?mg/0.01?cc (n?=?10). Total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood samples were measured and the oxidative stress index (OSI) was calculated. Also, corneal tissue histopathology was evaluated with caspase-3 and caspase-8 staining. Apoptotic activity was also evaluated.

Results: In blood samples, TAS, TOS, and OSI levels were not statistically significantly different (all p?>?0.05). Compared with the sham and control groups, TOS and OSI levels in cornea tissue were significantly different in the moxifloxacin group (all p?p?>?0.05). Compared with the sham and control groups, apoptotic activity was higher in the moxifloxacin group, in both immunohistochemical staining for caspase-3 and caspase-8.

Conclusions: Intracameral moxifloxacin injection seems to be safe systemically, but it may have toxic effects on corneal tissues, as suggested by oxidative stress parameters and a histopathological evaluation.     

Impact of 2.45 GHz microwave radiation on the testicular inflammatory pathway biomarkers in young rats: The role of gallic acid

The aim of this study was to investigate electromagnetic radiation (EMR) transmitted by wireless devices (2.45 GHz), which may cause physiopathological or ultrastructural changes, in the testes of rats. We addressed if the supplemental gallic acid (GA) may reduce these adverse effects. Six‐week‐old male Sprague Dawley rats were used in this study. Forty eight rats were equally divided into four groups, which were named: Sham, EMR only (EMR, 3 h day^?1 for 30 days), EMR + GA (30 mg/kg/daily), and GA (30 mg/kg/daily) groups. Malondialdehyde (MDA) and total oxidant status (TOS) levels increased (p = 0.001 for both) in EMR only group. TOS and oxidative stress index (OSI) levels decreased in GA treated group significantly (p = 0.001 and p = 0.045, respectively). Total antioxidant status (TAS) activities decreased in EMR only group and increased in GA treatment group (p = 0.001 and p = 0.029, respectively). Testosterone and vascular endothelial growth factor (VEGF) levels decreased in EMR only group, but this was not statistically significant. Testosterone and VEGF levels increased in EMR+GA group, compared with EMR only group (p = 0.002), and also increased in GA group compared with the control and EMR only group (p = 0.044 and p = 0.032, respectively). Prostaglandin E₂ (PGE₂) and calcitonin gene releated peptide (CGRP) staining increased in tubules of the testes in EMR only group (p < 0.001 for both) and decreased in tubules of the testes in EMR+GA group (p < 0.001 for all parameters). In EMR only group, most of the tubules contained less spermatozoa, and the spermatozoon counts decreased in tubules of the testes. All these findings and the regenerative reaction, characterized by mitotic activity, increased in seminiferous tubules cells of the testes in EMR+GA group (p < 0.001). Long term EMR exposure resulted in testicular physiopathology via oxidative damage and inflammation. GA may have ameliorative effects on the prepubertal rat testes physiopathology. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1771–1784, 2016.     

Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats

Context: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects.

Objective: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated.

Materials and methods: Male Wistar rats were pretreated with RA (10, 50 and 100?mg/kg, i.g.) for one week. On day 7, rats received APAP (500?mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined.

Results: APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6?±?0.21?nmol/mg) as well as a decrease in the contents of TAC (1.75?±?0.14?μmol/g), GSH (1.9?±?0.22?μmol/g) and GST) 3.2?±?0.28?U/mg). RA treatment decreased MDA (4.32?±?0.35?nmol/mg) but increased the contents of TAC (3.51?±?0.34?μmol/g), GSH (3.42?±?0.16?μmol/g) and GST (5.71?±?0.71?μmol/g) in APAP group. RA 100?mg/kg decreased ALT (91.5?±?1.5?U/L), AST (169?±?8.8?U/L) and CYP450 (3?±?0.2?nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group.

Discussion and conclusions: This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity.     

The effects of rutin on cisplatin induced oxidative retinal and optic nerve injury: an experimental study

Aim: To determine the role of rutin in prevention of cisplatin induced retinal and optic nerve injury in an experimental study.

Materials and methods: Totally 18 albino Wistar male rats were assigned into three groups, as follows: healthy controls (HC group), only cisplatin administered group for 14?days (CIS group), and rutin?+?cisplatin administered group for 14?days (RC group). Blood samples were obtained from animals just before the scarification. Serum malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), superoxide dismutase (SOD), interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) levels were investigated. The eyes were enucleated for histopathological evaluations of retina and optic nerve.

Results: MDA, MPO, IL-1β and TNF-α levels were statistically significantly higher (p?p?p?Conclusions: Concomitant rutin administration may prevent the detrimental effects of cisplatin on lipid peroxidation, oxidative stress and inflammation markers and may also avert the histopathological damage on retina and optic nerve. Further studies are warranted to determine the effects of cisplatin and rutin on eye.     

Polysaccharides from Cordyceps sinensis mycelium ameliorate exhaustive swimming exercise-induced oxidative stress

Context. Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae) is a famous medicinal fungus (mushroom) in Chinese herbal medicine. Polysaccharides from Cordyceps sinensis (CSP) have been identified as active ingredients responsible for its biological activities. Although many pharmacological actions of CSP have received a great deal of attention, research in this area continues.

Objective: The current study was designed to investigate the effects of CSP on exhaustive exercise-induced oxidative stress.

Materials and methods: The mice were divided into four groups: control (C), low-dose CSP treated (LC), intermediate-dose CSP treated (IC) and high-dose CSP treated (HC). The treated groups received CSP (100, 200 and 400?mg/kg, ig), while the control group received drinking water for 28?days, followed by being forced to undergo exhaustive swimming exercise, and some biochemical parameters including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured using detection kits according to the manufacturers’ instructions.

Results: Compared with the C group, exhaustive swimming time was significantly prolonged in the LC, IC and HC groups (p?p?p?p?p?Discussion and conclusion: The results obtained herein indicate that CSP could ameliorate exhaustive exercise-induced oxidative stress.     

Antioxidant activity of olive wine,a byproduct of olive mill wastewater

Context Although olive mill wastewater (OMWW) is a good source of bioactive phenolic compounds, disposing OMWW is a serious environmental challenge. Production of wine via fermenting OMWW may be a promising alternative to deal with OMWW. However, whether or not olive wine from OMWW still reserves its original bioactivities remains unclear.

Objective This study examines antioxidant activity of olive wine fermented from OMWW.

Materials and methods Hydroxytyrosol in olive oil was determined by HPLC. Total flavonoid, total polyphenol and in vitro antioxidant activities were measured by spectrophotometry. Aged mice were intragastricly administered 7, 14 and 28?mL/kg olive wine consecutively for 30 d. Afterward, levels of malonaldehyde (MDA), protein carbonyl, reduced glutathione (GSH) and activity of superoxide dismutase (SOD) were assayed in mouse plasma and liver.

Results Contents of hydroxytyrosol, total flavonoid and total polyphenol in olive wine were 0.14?±?0.01, 0.29?±?0.06 and 0.43?±?0.03?mg/mL, respectively. The IC₅₀ value of olive wine to scavenge DPPH and hydroxyl free radicals was 2.5% and 3.2% (v/v), respectively. Compared with the solvent control group, olive wine with a dose of 28?mL/kg remarkably lowered mouse MDA concentration in liver, and reduced protein carbonyl level in plasma (p?<?0.05). Meanwhile, olive wine at doses of 7 and 28?mL/kg notably enhanced SOD activity in both mouse plasma and liver (p?<?0.05). The beneficial effect on liver was superior to that of γ-tocopherol.

Conclusion The study demonstrated that olive wine from OMWW has potential for treating oxidative stress-associated diseases.     

Assessment of luteolin isolated from Eclipta alba leaves in animal models of epilepsy

Context: Eclipta alba (Linn) Hassk. (Asteraceae) has been reported to be a nerve tonic and has been used to treat epilepsy in folk medicine.

Objective: The present study isolates and characterizes luteolin from E. alba and evaluates its antiepileptic potential in chemically induced acute and chronic models in mice.

Materials and methods: The methanol extract (16.85% w/w) of E. alba leaves was subjected to fractionation for isolation of luteolin. In acute pentylenetetrazole (PTZ) model, luteolin (5, 10, 20?mg/kg, i.p.) was administered 30?min prior to PTZ injection (100?mg/kg) in Swiss albino mice. Kindling was induced by chronic administration of PTZ (35?mg/kg) on every alternate day (48 days). Luteolin was investigated on the course of kindling development and oxidative stress markers [reduced glutathione (GSH) and malondialdehyde (MDA)] in kindled mice.

Results: Single-dose pretreatment with luteolin (10 and 20?mg/kg, i.p.) was found to be effective in an acute PTZ model (100% protection from mortality) and it did not exhibit any effect on motor coordination at the same doses. PTZ-induced kindling was significantly (p?p?p?Discussion and conclusion: The results of the present study demonstrated that luteolin had an anticonvulsant effect in an acute PTZ model. Luteolin exhibited and inhibitory effect on the course of kindling and associated oxidative stress and hence could be a potential molecule in the treatment of epilepsy.     

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS

Context: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential.

Objective: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots.

Materials and methods: Hepatotoxicity was induced by oral administration of APAP (750?mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25?mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2?h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis.

Results: In WRF-treated group, there was significant and dose-dependent (p?<?0.01 and p?<?0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p?<?0.01 and p?<?0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p?<?0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p?<?0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment.

Conclusion: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.     

Antidiabetic mechanism of Coptis chinensis polysaccharide through its antioxidant property involving the JNK pathway

Abstract

Context: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae) polysaccharide (CCPW) has been reported. However, its molecular mechanism remains unclear.

Objective: An attempt was made to further verify the antidiabetic activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism of antidiabetic activity.

Materials and methods: Male Wistar rats were fed with high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4) were investigated.

Results: FBG level of diabetic rats could be significantly inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of 200, 100, and 50?mg/kg b.w., respectively (p?<?0.01). CCPW also could significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%, respectively (p?<?0.05 or p?<?0.01). CCPW showed an obvious antioxidant effect through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA contents (p?<?0.05 or p?<?0.01). Furthermore, CCPW could inhibit JNK and phospho-IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared with those in the DM group (p?<?0.05 or p?<?0.01).

Discussion and conclusion: CCPW can produce antidiabetic activity in rats with T2DM through its antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.     

Protective effects of caffeic acid phenethyl ester on the dose‐dependent acute nephrotoxicity with paraquat in a rat model

Paraquat (PQ), which is used extensively as a potent herbicide throughout the world, is highly toxic in humans. We aimed to determine PQ‐induced biochemical and histologic changes in the kidneys, and to evaluate the ability of the protective effects of caffeic acid phenethyl ester (CAPE) against PQ‐induced injury in rats. Forty‐eight rats were divided into eight groups of six: Group 1: Control; Group 2: 10 μmol/kg CAPE; Group 3: 15 mg/kg PQ; Group 4: 30 mg/kg PQ; Group 5: 45 mg/kg PQ; Group 6: 15 mg/kg PQ+CAPE; Group 7: 30 mg/kg PQ+CAPE; Group 8: 45 mg/kg PQ+CAPE. PQ and CAPE were injected intraperitoneally. The levels of the total oxidant status (TOS) and total antioxidant status (TAS) were determined in the supernatants of the excised left kidney. Right kidney tissue of each rat was removed to obtain a histologic score. When PQ‐administrated (15, 30, 45) groups compared with other groups, TOS values were found to be significantly higher (p < 0.01). PQ (15, 30, 45) groups had significantly diminished values of TAS than the other groups (p < 0.001). Of histologic score evaluation, only the PQ45 group had a significantly higher value than the sham, and CAPE groups (p < 0.05). Moreover, in CAPE+PQ45 group, the level of histologic score was decreased compared to PQ45 group (p < 0.001). In conclusion, the evaluation of the data suggests that CAPE can be used to prevent the acute effects of PQ nephrotoxicity. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 375–381, 2015.