Protective role of citronellol on antioxidant enzymes and oxidative damage induced by gentamicin in experimental nephrotoxic rats.

BACKGROUND: Gentamicin leads to nephrotoxicity with increasing oxidative stress. In the present research the role of citronellol on oxidative damage induced by gentamicin in nephrotoxic rats was evaluated. METHODS AND RESULTS: Forty-twomale Wistar rats were randomly divided into seven equal groups; healthy control, gentamicin, DMSO, citronellol 50, citronellol 100, citronellol 200 and vitamin E. The animals were anesthetized after 12 days of treatment. Kidney and serum samples were received for biochemical, histological changes, and gene expression assessments. The levels of serum glutathione (GSH), serum and kidney glutathione peroxidase (GPX) and the expression of GPX gene against gentamicin group were increased in citronellol treatment groups. The levels of serum and kidney malondialdehyde (MDA), urine protein, serum creatinine and the gene expression of inflammatory factors including tumor necrosis factor-alpha (TNF-α) and Interleukin 6 (IL-6) against gentamicin group were decreased in these groups. Moreover, recuperation in histological alterations was shown in three groups receiving citronellol compared to the gentamicin group. CONCLUSIONS: Citronellol with its antioxidant and anti-inflammatory properties can decrease kidney damage caused by nephrotoxicity induced by gentamicin.

Gallic acid improves liver cirrhosis by reducing oxidative stress and fibrogenesis in the liver of rats induced by bile duct ligation.

Disturbance in the production and excretion of bile acid causes cholestatic liver disease. Liver cirrhosis is a disease that occurs if cholestasis continues. This study evaluated the protective effect of gallic acid (GA) on liver damage caused by biliary cirrhosis. Rats were randomly divided into 4 groups, each with 8 subjects: 1) control, 2) BDL, 3) BDL + GA 20, and 4) BDL + GA 30. The rats were anesthetized 28 days after the BDL, followed by collecting their blood and excising their liver. Their serum was used to measure liver enzymes, and the liver was used for biochemical analysis, gene expression, and histopathological analysis. Serum levels of liver enzymes, total bilirubin, liver Malondialdehyde level (MDA), expression of inflammatory cytokines and caspase-3, necrosis of hepatocytes, bile duct proliferation, lymphocytic infiltration, and liver fibrosis showed an increase in the BDL group compared to the control group (p < 0.05). In addition, BDL decreased the activity of liver antioxidant enzymes and glutathione (GSH) levels compared to the control group (p < 0.05). The groups receiving GA indicated a decrease in liver enzymes, total bilirubin, MDA, the expression of inflammatory cytokines and caspase-3, and a reduction in liver tissue damage compared to the BDL group (p < 0.05). The level of GSH in the BDL + GA 20 group showed a significant increase compared to the BDL group (p < 0.05). Moreover, it was found that GA, with its anti-fibrotic and anti-inflammatory properties, reduces liver damage caused by biliary cirrhosis.

Antidiabetic, hypolipidemic, and antioxidant activities of Pistacia atlantica: A systematic review and meta-analysis of preclinical studies.

To determine the pharmaceutical applications, we assessed the evidence from preclinical studies about the hypoglycemic, hypolipidemic, and antioxidant potential of Pistacia atlantica (PA) as a natural source for prevention and treatment of diabetes. A comprehensive literature search of the articles published until March 12, 2022 was conducted on PubMed, Embase, Web of Sciences, and Scopus databases, using relevant keywords. This meta-analysis included 12 articles that examined the blood glucose (BG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA) and superoxide dismutase (SOD). A random-effects model was used to estimate the pooled effect size. Findings indicated that PA supplementation significantly decreased BG, HOMA-IR, TC, TG, and MDA, and increased insulin and SOD in diabetic animals compared with control group (p < .05). However, PA supplementation had no significant effects on HDL-C (p > .05). The subgroup analysis also confirmed the beneficial effect of PA supplementation with longer duration (>4 weeks) and higher doses (≥100 mg/kg/day) as well as in the extract type. The studies have heterogeneity associated with methodological diversity and there were some concerns about the risk of bias, especially about randomization and blind outcome assessment. This meta-analysis provided convincing evidence for antidiabetic, hypolipidemic, and antioxidant activity of PA in animals. Further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Exogenous glutathione protects against gentamicin-induced acute kidney injury by inhibiting NF-κB pathway, oxidative stress, and apoptosis and regulating PCNA.

This study was designed, for the first time, to examine the possible nephroprotective effects of exogenous glutathione (EGSH) (100 mg/kg, intraperitoneally) on gentamicin-induced acute kidney injury (GM-induced AKI). EGSH reduced renal histopathological changes, inflammatory cell infiltration, and improved renal dysfunction in rats with AKI. EGSH ameliorated GM-induced renal oxidative stress by promoting the renal activities of catalase, glutathione peroxidase, and superoxide dismutase and diminishing renal malondialdehyde and serum nitric oxide levels. Interestingly, EGSH inhibited intrinsic apoptosis by downregulating Bax and caspase-3 and upregulating Bcl2 in the kidney of rats with AKI. EGSH decreased GM-induced inflammatory response as reflected by a remarkable decrease in the protein expressions of NF-κB-p65, IL-6, TNF-α, and iNOS and a considerable diminish in myeloperoxidase activity. Finally, EGSH markedly declined proliferative cell nuclear antigen (PCNA) protein expression in the animals with AKI. In summary, EGSH alleviated AKI in rats intoxicated with GM, partially by inhibiting oxidative stress, NF-κB pathway, and intrinsic apoptosis and regulating PCNA.

Dose-Dependent Effects of Astaxanthin on Ischemia/Reperfusion Induced Brain Injury in MCAO Model Rat.

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin.

Leech therapy (Hirudo medicinalis) attenuates testicular damages induced by testicular ischemia/reperfusion in an animal model.

BACKGROUND: Testicular torsion/detorsion triggers tissue ischemia/reperfusion, leading to reactive oxygen species overgeneration and apoptosis. The saliva of leeches is full of anti-inflammatory, anticoagulants, antioxidants, and antimicrobial agents. Therefore, this study aimed to assess the protective mechanism of leech therapy on testicular ischemia/reperfusion damage. METHODS: 18 adult male rats were randomly divided into three groups: 1-Sham-operated group (SO). 2-Torsion/detorsion (T.D) group: two hours of testicular torsion with two hours of testicular detorsion was performed. 3-Torsion/detorsion + Leech therapy (TDL) group. Sperm parameters (motility, vitality, morphology, and concentration), oxidative stress biomarkers (MDA, CAT, GPx, and TAC), histopathological factors (Mean seminiferous tubular diameter, Germinal epithelial cell thickness, Testicular capsule thickness, Johnson's score, and Cosentino's score), and immunohistochemical markers for apoptosis detection (Bax, Bcl-2, and Caspase-3) were measured. RESULTS: There was a significant difference for all sperm parameters in the T. D group compared to the sham group. Leech therapy significantly increased progressive motility and normal morphology and reduced non-progressive motility. In the TDL group, MDA concentration significantly reduced, and levels of GPx, TAC, and CAT remarkably increased. All evaluated histopathological parameters in the TDL group significantly increased compared to the T. D group except for the testicular capsule thickness. T. D notably increased the expression of Bax and Caspase-3, while the treatment group slowed the rate of apoptosis compared to the control group. Bcl-2 expression in the T. D group was significantly lower than that in the sham group. Leech therapy increased the Bcl-2 expression. CONCLUSION: Leech therapy attenuates damages to testicular tissue following torsion/detorsion due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, it can be considered as an effective remedy for testicular ischemia/reperfusion.

Co-administration of Salvia miltiorrhiza and verapamil inhibits detrimental effects of torsion/detorsion on testicular tissue in rats.

Testicular torsion/detorsion is one of the important emergencies that requires fast surgical intervention. This study aimed to investigate the effects of Salvia miltiorrhiza hydroalcoholic extract combined with verapamil on testicular ischaemia/reperfusion damage in Wistar albino rats. All animals were distributed in 3 groups (n = 8), including the sham-operated group, torsion/detorsion (TD) group and torsion/detorsion + pretreatment with 200 mg/kg Salvia miltiorrhiza extract combined with 0.3 mg/kg verapamil (SMV) group. Oxidative stress biomarkers (MDA, GPx, CAT and TAC) both in plasma and testicular tissue, sperm parameters (motility, vitality, concentration and morphology) and histopathological parameters (MSTD, GECT, Johnson's score, Cosentino's score and testicular cell thickness) were assessed in all groups. Ischaemia/reperfusion significantly increased MDA and decreased GPx, CAT and TAC levels (p < .05). Pretreatment with SMV significantly increased GPx, CAT and TAC levels (p < .05). SMV group increased progressive sperm motility and vitality and reduced non-progressive motility of spermatozoon (p < .05). Testicular torsion significantly decreased all histopathological parameters compared to the sham group (p < .05). SMV pretreatment remarkably increased MSTD, GECT and Cosentino's score in comparison with the TD group (p < .05). A combination of Salvia miltiorrhiza with verapamil could reduce damages triggered by testicular torsion detorsion and improve sperm functionality parameters and oxidative stress defence systems.

Serum Levels of Chemerin, Apelin, and Adiponectin in Relation to Clinical Symptoms, Quality of Life, and Psychological Factors in Irritable Bowel Syndrome.

BACKGROUND: Adipokines have endocrine roles in metabolism and immunity. Dysregulation of adipokine levels is associated with several diseases with chronic inflammation. We aimed to assess the serum concentrations of chemerin, apelin, and adiponectin in irritable bowel syndrome (IBS). Furthermore, we evaluated the possible association of these adipokines with clinical symptoms, quality of life (QoL), and psychological factors. MATERIALS AND METHODS: In this case-control study, 114 male and female IBS patients were recruited from outpatient clinics. Along with the IBS patients, 114 sex and age-matched healthy volunteers were recruited. Patients filled in the questionnaires of the IBS severity scoring system (IBSSS), gastrointestinal (GI) and somatic symptoms, IBS specific QoL (IBS-QoL), and psychological disorders, and went to the lab for blood sampling. RESULTS: Serum levels of both adiponectin and apelin were significantly (P=0.04, 0.03, respectively) lower, whereas chemerin was significantly (P=0.01) higher in IBS patients. Chemerin was higher in IBS-D compared with both IBS-C and IBS-A, while apelin and adiponectin were not different between subtypes. After adjustments for confounders only, chemerin had a positive association with IB severity scoring system and GI symptoms. Furthermore, chemerin had positive associations, whereas apelin and adiponectin had inverse associations with somatic symptoms and psychological factors. There were no significant associations between adipokines including chemerin, apelin, and adiponectin, and IBS-QoL. CONCLUSIONS: Chemerin had significant associations with both the severity of clinical symptoms and psychological factors in IBS; thus, it could be considered as a potential therapeutic target in these patients; however, further studies are needed.

Effects of Pistacia atlantica on Oxidative Stress Markers and Antioxidant Enzymes Expression in Diabetic Rats.

INTRODUCTION: Diabetes mellitus (DM) affects many patients all over the world. It involves different parts of the body, such as brain, eyes, kidneys, vessels, and so on. The lack of balance between free radicals and antioxidants is a possible mechanism involved in the pathogenesis of diabetes. Antioxidant treatment, especially natural forms, can be a beneficial solution. Therefore, we evaluated the effects of Pistacia atlantica oleoresin (PAO) on oxidative stress markers and antioxidant enzymes expression in diabetic rats. METHOD: Fifty adult male Wistar rats were allotted randomly into five groups as follow: control group, diabetic control group, glibenclamide control group, diabetic glibenclamide group, diabetic treated group with 200 mg/kg PAO. Then PAO was prepared and analyzed by gas chromatography/mass spectroscopy (GC/MS). LD50 was also estimated for essential oil. Oxidative stress markers and antioxidant enzyme including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were also measured. The expression of GPx, CAT, and SOD genes was investigated using real-time polymerase chain reaction (PCR). RESULTS: The main constituents of essential oil gum were beta-pinene (29.38%), followed by alpha-pinene (18.15%), myrcene (7.36%), trans-pinocarveol (7.15%), and camphene (4.12%). Diabetes induced an increased level of MDA (69.92 ± 3.92 vs. 43.76 ± 3.73) and decreased levels of GSH (2.57 ± 0.40 vs. 7.05 ± 1.59), GPx (11.66 ± 2.2 vs. 16.38 ± 2.1), CAT (12.17 ± 3.38 vs. 18.7 ± 2.66), and SOD (0.78 ± 0.67 vs. 2.41 ± 0.46). In contrast, PAO treatment significantly decreased MDA (54.59 ± 12.54 vs. 69.92 ± 3.92) and increased GSH (4.5 ± 0.89 vs. 2.57 ± 0.40), GPx (25.86 ± 5.37 vs. 11.66 ± 2.2), CAT (22.69 ± 0.36 vs. 12.17 ± 3.38), and SOD (3.65 ± 1.08 vs. 0.78 ± 0.67) (p < 0.05). Moreover, our results indicated that both GPx and CAT mRNA levels significantly increased approximately 4.46 and 6.23 times in rats fed with 200 mg/kg of PAO, more than that of the healthy control group, respectively (p < 0.01 and p < 0.001, respectively). Also, the average expression level of SOD was also significantly 1.57 higher in rats fed with 200 mg/kg of PAO in comparison to the diabetic control group (p < 0.05). CONCLUSION: The results indicated that PAO could be propose as an agent that protects the body against diseases that are associated with oxidative stress.

Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against peripheral nerve transection-induced apoptosis.

Objectives: Recent studies revealed the neuroprotective effects of epigallocatechin-3-gallate (EGCG) on a variety of neural injury models. The purpose of this study was to determine the neuroprotective effects of EGCG following sciatic nerve transection (SNT). Methods: Rats were randomly divided into four groups each as follows: Sham-operated group, SNT group, and Pre-EGCG (50-mg/kg, i.p., 30 minutes before nerve transection and followed for 3 days) and Post-EGCG (50-mg/kg, i.p., 1 hour after nerve transection and followed for 3 days) groups. Spinal cord segments of the sciatic nerve and related dorsal root ganglions were removed four weeks after nerve transection for the assessment of malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, immunohistochemistry of caspase-3, cyclooxygenase-2 (COX-2), S100beta (S100B), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Results: MDA levels were significantly decreased, and SOD and CAT activities were significantly increased in EGCG-treated rats after nerve transection. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the EGCG-treated rats after nerve transection. Also, EGCG significantly increased S100B expression. Discussion: We propose that EGCG may be effective in the protection of neuronal cells against retrograde apoptosis and may enhance neuronal survival time following nerve transection.

Juglans Regia L. Leaf Extract Attenuates Diabetic Nephropathy Progression in Experimental Diabetes: An Immunohistochemical Study.

BACKGROUND: There is accumulating evidence that Juglans regia L. (GRL) leaf extract has hypoglycemic and antioxidative properties. The present study aimed to investigate the protective effects of GRL leaf extract against diabetic nephropathy (DN). METHODS: In total, 28 male adult Sprague-Dawley rats were used. The DN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats received intragastric administration of GRL leaf extract (200 mg/kg/day) starting 1 week (preventive group) and 4 weeks (curative group) after the onset of hyperglycemia up to the end of the 8th week, whereas other diabetic rats received only isotonic saline (diabetic group) as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic nephropathy, various parameters of apoptosis and inflammation were assessed. Statistical analysis was performed using the SPSS software, version 15.0. The data were compared between the groups using the Tukey's multiple comparison test and the analysis of the variance. P values ˂0.05 were considered statistically significant. RESULTS: Fasting blood sugar (FBS) levels (P=0.001) and histopathological changes in the kidney of diabetic rats attenuated after GRL leaf extract consumption. Greater caspase-3 (P=0.004), COX-2 (P=0.008), PARP (P=0.007), and iNOS (P=0.005) expression could be detected in the STZ-diabetic rats, which were significantly (P=0.009) attenuated after GRL leaf extract consumption. In addition, attenuation of lipid peroxidation in the diabetic rats was detected after GRL consumption (P=0.01). CONCLUSION: GRL leaf extract exerts preventive and curative effects against diabetic nephropathy.

Neuroprotective effects of hyperbaric oxygen (HBO) therapy on neuronal death induced by sciatic nerve transection in rat.

BACKGROUND: Recent studies shows that hyperbaric oxygen (HBO) therapy exerts some protective effects against neural injuries. The purpose of this study was to determine the neuroprotective effects of HBO following sciatic nerve transection (SNT). METHODS: Rats were randomly divided into five groups (n = 14 per group): Sham-operated (SH) group, SH + HBO group, SNT group, and SNT + pre- and SNT + post-HBO groups (100% oxygen at 2.0 atm absolute, 60 min/day for five consecutive days beginning on 1 day before and immediately after nerve transaction, respectively). Spinal cord segments of the sciatic nerve and related dorsal root ganglions (DRGs) were removed 4 weeks after nerve transection for biochemical assessment of malodialdehyde (MDA) levels in spinal cord, biochemical assessment of superoxide dismutase (SOD) and catalse (CAT) activities in spinal cord, immunohistochemistry of caspase-3, cyclooxigenase-2 (COX-2), S100beta (S100ß), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in spinal cord and DRG. RESULTS: The results revealed that MDA levels were significantly decreased in the SNT + pre-HBO group, while SOD and CAT activities were significantly increased in SNT + pre- and SNT + post-HBO treated rats. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the HBO-treated rats after nerve transection. Also, HBO significantly increased S100ß expression. CONCLUSIONS: Based on these results, we can conclude that pre- and post-HBO therapy had neuroprotective effects against sciatic nerve transection-induced degeneration.

Dietary Myrtle (Myrtus communis L.) improved non-specific immune parameters and bactericidal activity of skin mucus in rainbow trout (Oncorhynchus mykiss) fingerlings.

The present study examined the effects of dietary Myrtle (Myrtus communis L.) on non-specific immune parameters and bactericidal activity of skin mucus in rainbow trout (Oncorhynchus mykiss) fingerlings. Three hundred and sixty fingerlings (6.50 ± 0.55 g (were distributed in twelve cages (65 × 65 × 65 cm) with a metal framework. The study included four treatments repeated in triplicates. The treatments were feeding trouts with experimental diets containing different levels (0, 0.5, 1 and 1.5%) of Myrtle powder. The fingerlings were fed on experimental diet for sixty days and then skin mucus non-specific immune parameters as well as bactericidal activity were measured. At the end of the trial, the highest skin mucus soluble protein level was observed in group fed with 1.5% Myrtle (P < 0.05). The alkaline phosphatase (ALP) activity was significantly increased in fish groups fed 1 and 1.5% Myrtle compared with the control group (P < 0.05). However, evaluation of skin mucus lysozyme activity showed no significant difference between treatments and control group (P > 0.05). Also, no antibacterial activity was detected against Escherichia coli, Staphylococcus aureus and Salmonella enterica in all treatments and control group. Whereas skin mucus of rainbow trout showed antimicrobial activity against fish pathogens (Aeromonas hydrophila and Yersinia ruckeri) in 1 and 1.5% Myrtle treatments. These results indicated beneficial effects of dietary Myrtle on mucosal immune parameters of fingerling rainbow trout.

Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

BACKGROUND: Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. METHODS: The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. RESULTS: Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. CONCLUSION: Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy.

Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An Experimental Study.

BACKGROUND: Deltamethrin (DM) is a synthetic pyrethroid insecticide which can lead to pathological effects in mammals through oxidative stress. On the other hand, virgin olive oil (VOO) is a rich source of phenolic compounds with antioxidants. The aim of the present study was to determine the protective effects of VOO against DM-induced hepatotoxicity. METHODS: Thirty-six mice were randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the biochemical analysis of malondialdehyde and total antioxidant capacity levels were performed in the liver samples 5 weeks after gavaging. Statistical analysis was performed using SPSS, version 15. The data were compared between the groups using the Tukey multiple comparison tests and the analysis of the variance. A P value <0.05 was considered significant. RESULTS: The malondialdehyde level in the liver was increased in the DM group (71.18±0.01), whereas it was significantly (P=0.001) decreased after VOO administration in the DM plus VOO group (39.59±2.43). While the total antioxidant capacity level in the liver was decreased in the DM group (3.05±0.05), it was significantly increased (P=0.03) after VOO administration in the DM plus VOO group (3.95±0.04). A greater expression of caspase-3 (P=0.008), COX-2 (P =0.004), and PARP (P 0.006) could be detected in the DM group, while it was significantly (P=0.009) attenuated in the DM plus VOO group. Also, the degeneration of hepatocytes, which was detected in the DM group, was attenuated after VOO consumption. CONCLUSIONS: VOO exerted protective effects against DM-induced hepatotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and antioxidative properties.

Aspirin Resistance in Different Doses by Bleeding Time and Urinary 11-dehydro-thromboxane B2.

The aim of the present study was the evaluation bleeding time (BT) in comparison to Urinary 11-dehydro thromboxane B2 (TXB2) regarding different ASA frequent dosages used in Borujerd city. This is a double blind randomized clinical trial on 370 subjects aged 35 years and older, referred to clinical offices in Borujerd. All ischemic heart disease's patients were randomly assigned to 4 ASA dose groups (80 mg, 81 mg, 100 mg and 325 mg) and one group-matched control group without any IHD. BT was measured by Ivy method; TXB2 was measured in a urine sample, both at least 5 days after ASA consumption. Probale AR was indicated if TXB2 was normal or higher than normal higher limit values, or BT was normal or lower than normal higher values. (IRCT201202026958N3) Probale AR was present in 37.6% and 64% resistance by BT and TXB2, respectively. All 4 treated groups had higher TXB2 levels than the control group/normal values (p>0.05). Also, urinary TXB2 level correlated positively with BT. Given the simplicity and low costs of its performance it might be of some potential use in developing countries. However, due to IVY method limitations it cannot be perceived as a tool to assess such specific aspects of platlat function or aspirin resistance.

Serum paraoxonase 1 status and its association with atherogenic indexes in gentamicin-induced nephrotoxicity in rats treated with coenzyme Q10.

Coenzyme Q10 is a natural antioxidant and scavenger of free radicals. In the present study, we examined the effect of coenzyme Q10 on paraoxonase 1 (PON1) activity, lipid profile, atherogenic indexes and relationship of PON 1 activity by high-density lipoprotein (HDL) and atherogenic indexes in gentamicin (GM)-induced nephrotoxicity rats. Thirty Sprague-Dawley rats were divided into three groups to receive saline; GM, 100 mg/kg/d; and GM plus coenzyme Q10 by 15 mg/kg i.p daily, respectively. After 12 days, animals were anaesthetized, blood samples were also collected before killing to measure the levels of triglyceride (TG), cholesterol (C), low-density lipoprotein (LDL), very low density lipoprotein (VLDL), HDL, atherogenic indexes and the activities of PON1 of all groups were analyzed. Data were analyzed by non-parametric Mann-Whitney test (using SPSS 13 software). Coenzyme Q10 significantly decreased TG, C, LDL, VLDL, atherogenic index, atherogenic coefficient and cardiac risk ratio. HDL level and PON1 activity were significantly increased when treated with coenzyme Q10. Also, the activity of PON 1 correlated positively with HDL and negatively with atherogenic coefficient, cardiac risk ratio 1 and cardiac risk ratio 2. This study showed that coenzyme Q10 exerts beneficial effects on PON1 activity, lipid profile, atherogenic index and correlation of PON 1 activity with HDL and atherogenic index in GM -induced nephrotoxicity rats.

Monoterpene linalool restrains gentamicin-mediated acute kidney injury in rats by subsiding oxidative stress, apoptosis, and the NF-κB/iNOS/TNF-α/IL-1ß pathway and regulating TGF-ß.

The clinical use of gentamicin (GM) is restricted by its nephrotoxic effects. This study aimed for the first time to elucidate the ameliorative effects of the monoterpene linalool (Lin) against GM-mediated acute kidney injury in rats. A total of thirty-two rats were subdivided into four equal groups: control (saline), Lin (100 mg/kg/day), GM (100 mg/kg/day), and GM + Lin (100 and 100 mg/kg/day). Lin and GM were intraperitoneally administered for 12 days. Our results illustrated that Lin ameliorated GM-mediated renal histopathological abnormalities and reduced serum urea and creatinine levels in rats exposed to GM. Lin treatment mitigated oxidative stress in nephrotoxic animals as manifested by reducing serum and renal levels of malondialdehyde and increasing the activities of serum and renal glutathione peroxidase and renal catalase. Moreover, Lin markedly inhibited GM-triggered inflammation by downregulating NF-κB, iNOS, TNF-α, and IL-1ß and reducing renal myeloperoxidase activity and nitric oxide levels. Interestingly, Lin repressed GM-induced apoptosis, as reflected by a marked downregulation of Bax and caspase-3 expression, concurrent with the upregulation of Bcl2 expression. Finally, Lin administration led to a significant downregulation of TGF-ß expression in nephrotoxic animals. In summary, Lin ameliorated GM-mediated nephrotoxicity in rats, at least through its antioxidant, anti-inflammatory, and anti-apoptotic activities and by modulating TGF-ß.

The protective effects of alpha-pinene on high glucose-induced oxidative stress and inflammation in HepG2 cells.

Objectives: Hyperglycemia, a prevalent metabolic condition observed in diabetes, leads to oxidative damage, inflammatory responses, and other consequences. Natural compounds alleviate the adverse impacts of diabetes. We aimed to explore the effects of alpha-pinene (AP) as a monoterpene on oxidative damage and inflammation caused by high glucose (HG) in the human hepatocellular liver carcinoma (HepG2) cell line. Materials and Methods: The HepG2 cells were subjected to non or HG concentration (50 mM) and treated with or without AP (8, 16, and 32 µg/ml) for 48 hr. The effect of treatments on cellular viability, malondialdehyde (MDA), glutathione (GSH), and activity of anti-oxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), was determined. The gene expression levels of nuclear factor-κß (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and dipeptidyl peptidase-4 (DPP-4) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: HG exposure significantly increased cell death, MDA formation, and depletion of GSH content and GPx, CAT, and SOD activity (P<0.05). We have also seen a significant induction in NF-κB, TNF-α, IL-6, and DPP-4 gene expression in hepatocytes under HG conditions (P<0.05). Interestingly, co-treatment with AP in a dose-dependent manner improved cell death and altered levels of MDA and GSH, and activity of GPx and CAT (P<0.05). AP could also modulate the gene expression of NF-κB and inflammatory biomarkers dose-dependently (P<0.05). Conclusion: Our findings suggested the protective effect of AP on hepatocytes under HG conditions through attenuating oxidative stress markers and suppression of inflammatory pathways.

Positive correlation between serum levels of adiponectin and homocysteine in pre-eclampsia.

AIM: The aims of the present study were to assess the correlation between homocysteine and adiponectin and the homocysteine-to-adiponectin ratio in pre-eclampsia compared with normal pregnant women. MATERIALS AND METHODS: The study population consisted of 30 women with pre-eclampsia and 30 normal pregnant women. Serum levels of total adiponectin and total homocysteine were assessed using commercially available enzyme-linked immunosorbent assay methods. Data are presented as median. RESULTS: Serum levels of total adiponectin correlated directly with total homocysteine in both pre-eclampsia (r = 0.48, P = 0.01) and normal pregnancy (r = 0.68, P = 0.001). The homocysteine-to-adiponectin ratio was increased significantly in pre-eclampsia compared with normal pregnancy (0.90 vs 0.70, P = 0.03). Compared with normal pregnancy, women with severe pre-eclampsia showed significant increase in total adiponectin (14.29 vs 10.24, P = 0.01), total homocysteine (13.80 vs 7.25, P = 0.000) and homocysteine-to-adiponectin ratio (0.92 vs 0.70, P = 0.02). Women with mild pre-eclampsia had higher values of total adiponectin (16.19 vs 10.24, P = 0.000) and total homocysteine (13.11 vs 7.25, P = 0.000) compared with normal pregnancy. No significant differences were observed between mild and severe pre-eclampsia. CONCLUSION: The present study showed a positive association between adiponectin and homocysteine in pre-eclampsia. The homocysteine-to-adiponectin ratio may be an informative biomarker for the disease diagnosis and therapeutic monitoring.