ABSTRACT
BACKGROUND: Ischemia is a condition in which blood flow to tissues is decreased or entirely stopped for various reasons. The reperfusion process exacerbates damage caused by ischemia in the organs and tissues. Reactive oxygen species (ROS) are mainly responsible for ischemia-reperfusion (IR) damage. ROS increase results in lipid peroxidation (LPO) and oxidative stress. In the literature, taxifolin reportedly suppresses ROS production. This study aimed to determine the effect of taxifolin, which is a flavonoid, on IR injury of the sciatic nerve in rats. METHODS: This study divided 30 albino Wistar rats into 3 groups: IR without medication (IR) group, taxifolin applied IR (TAX+IR) group, and only dissection made to the sciatic nerve sham group (SHAM). Sciatic nerve injury was induced by applying 2 hours of ischemia and 3 hours of reperfusion to the abdominal aorta and iliolumbar arteries. Biochemical and histopathologic investigations then were performed on sciatic nerve tissues. Malondialdehyde, total glutathione, glutathione reductase, and glutathione peroxidase were analyzed as oxidative stress markers, and tumor necrosis factor-α and interleukin-1ß levels were evaluated as inflammatory stress markers in biochemical tests. RESULTS: The IR group has statistically significantly high oxidant and cytokine levels and low antioxidant levels compared with the TAX+IR group. Taxifolin treatment was also shown to cause significant histopathologic improvement. CONCLUSIONS: We suggest that taxifolin may be effective in preventing IR injury of the sciatic nerve.
Subject(s)
Reperfusion Injury , Animals , Ischemia , Malondialdehyde , Oxidative Stress , Quercetin/analogs & derivatives , Rats , Rats, Wistar , Reperfusion , Reperfusion Injury/prevention & control , Sciatic NerveABSTRACT
Intestinal mucositis is an important problem in the patients receiving cancer treatment. We aimed to investigate the effect of anakinra, which is a well known anti-oxidant and anti-inflammatory agent, on methotrexate-induced small intestine mucositis in rats. Forty rats were divided into 4 groups with 10 in each group. The healthy group (HG) and the methotrexate group (MTXG) were given distilled water, while the methotrexate + anakinra 50 (MTX+ANA50) and the methotrexate + anakinra 100 (MTX+ANA100) groups were intraperitoneally administered 50 and 100 mg/kg of anakinra. After one hour, the MTXG, MTX+ANA50 and MTX+ANA100 groups were given oral methotrexate at a dose of 5 mg/kg. This procedure was repeated once a day for 7 days. After the rats had been sacrificed, the small intestine tissue of rats were removed for the assesment of biochemical markers, histopathological evaluation and gene expression analyze. Statistical analyses of the data were performed using one-way ANOVA. Malondialdehyde (MDA), myeloperoxidase (MPO) and interleukin-6 (IL-6) levels were significantly higher, whereas total glutathione (tGSH) levels were significantly lower in MTXG (P<0.001) compared to other groups. MTX also increased IL-1ß and TNF-α gene expression levels in MTXG (P<0.001). Inflammatory cell infiltration and damage to the villus were observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the MTX+ANA100 group. A dose of 100 mg/kg of anakinra prevented the increase of the biochemical markers and gene expression levels better than a dose of 50 mg/kg. Intestinal mucositis caused by MTX may be preventible by co-administered anakinra.
Subject(s)
Intestinal Diseases/chemically induced , Intestine, Small , Methotrexate/adverse effects , Mucositis/chemically induced , Animals , RatsABSTRACT
Purpose: Oxidative stress and inflammation have been demonstrated in the pathogenesis of methanol toxicity. Taxifolin has antioxidant and anti-inflammatory properties. In this study, we examined the protective effect of taxifolin against methanol-induced optic nerve toxicity. Materials and methods: Animals were divided into four groups (n = 6): healthy control group (HG), methotrexate (MTX) treated group, methotrexate + methanol treated group (MTX + M), and methotrexate + methanol + taxifolin treated group (MTX + M+T). MTX was administered to all groups except HG group 3 mg/kg via oral gavage for 7 d. After that 20% methanol was orally administered to the MTX + M and MTX + M+T group at a dose of 3 g/kg. After 4 h, taxifolin was orally administered to MTX + M+T group 50 mg/kg. Animals were sacrificed by high-dose thiopental anaesthesia, 8 h after taxifolin administration and biochemical studies were performed. Results: Malondialdehyde (MDA), total oxidant system, nuclear factor kappa B (NF-κB), and tumour necrosis factor-alpha levels were significantly higher in the optic nerve of MTX and MTX + M groups compared to HG group. Otherwise, total glutathione (tGSH) and total antioxidant system levels decreased in MTX and MTX + M groups according to the HG group. MDA, total oxidant system, NF-κB, and tumour necrosis factor-alpha levels were decreased in the MTX + M+T group and tGSH, and total antioxidant system levels increased in the MTX + M+T group according to the MTX + M group. Conclusions: These results indicate that taxifolin prevents oxidative and inflammatory optic nerve damage due to methanol exposure.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Methanol/toxicity , Optic Nerve Injuries/drug therapy , Quercetin/analogs & derivatives , Solvents/toxicity , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Glutathione/metabolism , Male , Malondialdehyde/metabolism , NF-kappa B/metabolism , Optic Nerve Injuries/chemically induced , Optic Nerve Injuries/metabolism , Oxidative Stress/drug effects , Quercetin/pharmacology , Quercetin/therapeutic use , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Purpose: Diabetic retinopathy (DR) is one of the leading causes of blindness. In DR patients, antioxidant defence is disrupted, and production of reactive oxygen species and pro-inflammatory cytokines such as interleukin 1ß (IL-1ß) and tumour necrosis factor alpha (TNF-α) increases. Taxifolin has been reported to suppress reactive oxygen species, IL-1ß and TNF-α production. The aim of this study is to biochemically and histopathologically examine the protective effect of taxifolin against DR damage induced by alloxan. Materials and methods: Alloxan received rats with a blood glucose level of ≥250 mg/dL were divided into taxifolin-treated (TAX) (n = 6), diabetic control (DC) (n = 6) groups. There were rats received only saline in non-diabetic control (NC) group (n = 6). Taxifolin (50 mg/kg) was orally administered to the TAX group rats. DC and NC rats received the same volume of saline as a solvent. This procedure was repeated once a day for 3 months. At the end of this period, animals were killed by high dose thiopental sodium anaesthesia. Histopathological examinations were then performed on excised rat eyes. Malondialdehyde (MDA), total glutathione (tGSH), IL-1ß and TNF-α levels were measured in obtained blood samples. Results: MDA, IL-1ß and TNF-α levels were significantly increased in blood samples of DC group rats with hyperglycemia induced by alloxan compared with NC group (p < 0.0001), and decreased in the TAX group compared with the DC group (p < 0.0001). The levels of tGSH were significantly decreased in blood samples of DC group rats compared with NC group (p < 0.0001), and increased in the TAX group compared with the DC group (p < 0.0001). Histopathologically, retinal ganglion cells of the TAX group had a slightly dilated and congested blood vessel, and severe damage was inflicted to the retinal ganglion cell layer of the DC group. Conclusions: Experimental results suggest that taxifolin may be beneficial in the treatment of DR.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetic Retinopathy/drug therapy , Quercetin/analogs & derivatives , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/pathology , Diabetic Retinopathy/blood , Diabetic Retinopathy/pathology , Glutathione/blood , Interleukin-1beta/blood , Male , Malondialdehyde/blood , Quercetin/pharmacology , Quercetin/therapeutic use , Rats, Wistar , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/pathology , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND: Oxidative stress and interleukin-1 beta (IL-1ß) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin. OBJECTIVES: The objective of this study was to investigate the effect of anakinra, which is an IL-1ß receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses. MATERIAL AND METHODS: The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1ß. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA). RESULTS: The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1ß gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1ß gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1ß at a dose of 100 mg/kg compared to a 50 mg/kg dose. CONCLUSIONS: Anakinra prevents oxidative kidney damage induced by cisplatin, in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.
Subject(s)
Antineoplastic Agents/toxicity , Antioxidants/pharmacology , Antirheumatic Agents/pharmacology , Cisplatin/toxicity , Interleukin 1 Receptor Antagonist Protein/pharmacology , Kidney Diseases/chemically induced , Kidney/drug effects , Protective Agents/pharmacology , Animals , Drug Administration Schedule , Glutathione/metabolism , Injections, Intraperitoneal , Kidney/metabolism , Malondialdehyde , Oxidative Stress/drug effects , Rats , Rats, WistarABSTRACT
Cystitis is defined as an inflammation of the bladder caused by a bacterial infection, and it can be dangerous and painful when it spreads through the internal organs. In this study, antioxidant effects of hydroxylfasudil (HF) at the enzymatic and molecular level on kidney and liver tissues in cystitis rat model, which is caused by inflammation of the rat bladder with a protamine sulphate (PS), was examined. Quantitative changes of reduced glutathione (GSH) and lipid peroxidation (LPO) levels, which are a marker for oxidative stress, were determined in rat kidney and liver tissues for each groups. And then molecular and biochemical impact of HF treatment on antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) in cystitis model were studied. The results suggest that HF could be beneficial to the renal and hepatic antioxidant system. Thus, HF might be used as a novel therapeutics agent to eliminate interstitial cystitis.
Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Antioxidants/pharmacology , Cystitis/drug therapy , Cystitis/metabolism , Kidney/drug effects , Liver/drug effects , Protamines/pharmacology , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/therapeutic use , Animals , Antioxidants/therapeutic use , Catalase/metabolism , Cystitis/chemically induced , Cystitis/pathology , Disease Models, Animal , Glutathione/metabolism , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Rats , Superoxide Dismutase/metabolismABSTRACT
Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1ß, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1ß and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.
Subject(s)
Analgesics/administration & dosage , Cisplatin/adverse effects , Neuralgia/chemically induced , Neuralgia/drug therapy , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/drug therapy , Thiamine Pyrophosphate/administration & dosage , Thiamine/administration & dosage , Analgesics/metabolism , Animals , Cisplatin/administration & dosage , Cisplatin/antagonists & inhibitors , Disease Models, Animal , Interleukin-1beta/metabolism , Male , Malondialdehyde/metabolism , Neuralgia/pathology , Peripheral Nervous System Diseases/pathology , Rats, Wistar , Sciatic Nerve/pathology , Thiamine/metabolism , Thiamine/pharmacology , Thiamine Pyrophosphate/metabolism , Thiamine Pyrophosphate/pharmacologyABSTRACT
The conversion of carbon dioxide (CO2 ) and bicarbonate (HCO3- ) to each other is very important for living metabolism. Carbonic anhydrase (CA, E.C.4.2.1.1), a metalloenzyme familly, catalyzes the interconversion of these ions (CO2 and HCO3- ) and are very common in living organisms. In this study, a series of novel 2-amino-3-cyanopyridines supported with some functional groups was synthesized and tested as potential inhibition effects against both cytosolic human CA I and II isoenzymes (hCA I and II) using by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. The structural elucidations of novel 2-amino-3-cyanopyridines were achieved by NMR, IR, and elemental analyses. Ki values of the novel synthesized compounds were found in range of 2.84-112.44 µM against hCA I and 2.56-31.17 µM against hCA II isoenzyme. While compound 7d showed the best inhibition activity against hCA I (Ki : 2.84 µM), the compound 7b demonstrated the best inhibition profile against hCA II isoenzyme (Ki : 2.56 µM).
Subject(s)
Aminopyridines/chemical synthesis , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrases/chemistry , Humans , KineticsABSTRACT
OBJECTIVES: The aim of this paper is to determine the oxidative-antioxidative status and levels of soluble interleukin-2 recep-tor (sIL-2R) in serum of patients with different types of HPV infections and to compare it with patients who are negative for HPV. MATERIAL AND METHODS: A total of 80 women were divided into three groups as follows: Group 1 consisted of 25 women who were positive for HPV types 16 or 18; Group 2 consisted of 25 women who were positive for other types of HPV includ-ing type 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68; Group 3 consisted of 30 patients who were negative for HPV as a control group. Serum sIL-2R and plasma oxidative stress index (OSI) were analyzed. RESULTS: Serum sIL-2R levels were significantly higher in group 1 compared to group 2 and 3. OSI was found significantly increased in groups 1 and 2 compared to group 3. Also, we found a weak positive correlation between IL-2R and OSI. CONCLUSION: sIL-2R and oxidative stress may have a role in HPV infection, especially in case of high-risk types.
Subject(s)
Oxidative Stress , Papillomavirus Infections/blood , Receptors, Interleukin-2/blood , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Papillomaviridae/classificationABSTRACT
Interleukin-33 (IL-33) is a novel cytokine involved in diabetes mellitus (DM) but its role in diabetic ovarian injury is unknown. As IL-33 is modulated by apoptosis, we aimed at investigating the effect of diabetes on ovaries in terms of evaluating apoptosis and IL-33 in a rat model. In this prospective experimental study, 16 female, nonpregnant Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into two groups. Group 1 included eight healthy nondiabetic rats as controls and group 2 included eight rats in which diabetes was induced by intraperitoneal (i.p) injection of streptozotocin (STZ). After overt DM occurred (blood glucose >400 mgr/dl), all animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Serum levels of IL-33 and ovarian IL-33 and caspase-3 immunoexpressions were assessed. Immunoexpressions of caspase-3 and IL-33 were significantly higher in ovarian stromal cells of the diabetic rats compared to the controls. Also, in diabetic group, serum IL33 levels were significantly higher than the control group. In conclusion, increased IL-33 was observed both in serum and ovaries of STZ-induced diabetic rats as well as increased apoptosis in these diabetic rats. IL-33 may contribute to the apoptosis in diabetic ovarian injury.
Subject(s)
Apoptosis/physiology , Diabetes Mellitus, Experimental/metabolism , Interleukin-33/metabolism , Ovary/metabolism , Animals , Blood Glucose/metabolism , Caspase 3/metabolism , Diabetes Mellitus, Experimental/pathology , Female , Fibrosis/metabolism , Fibrosis/pathology , Ovary/pathology , Oxidative Stress/physiology , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVES: The objective of this study is to investigate and evaluate the effect of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats with methotrexate (MTX) through biochemical, gene expression, and histopathological examinations. METHODS: Experimental animals were divided into a healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group that received MTX (MTXG). The HREM and HREG groups of rats was administered 50 mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This procedure was repeated for 1 month. At the end of this period, all of the animals were sacrificed with a high dose of anesthesia. Then, the amounts of malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed oropharyngeal tissues. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) gene expressions were measured, and all the tissues were studied histopathologically. RESULTS: The amount of MDA was significantly increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). MTX significantly decreased the amount of tGSH in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers in the animal group in which the levels of MDA, IL-1ß, and TNF-α were high and the level of tGSH was low. However, histopathologic examination revealed mucin pools in wide areas due to ruptured oropharynx glands, and proliferated, dilated, and congested blood vessels and dilated ductal structures in some areas. CONCLUSION: HRE protected oropharyngeal oxidative damage induced by MTX. As an inexpensive and natural product, HRE has important advantages in the prevention of oropharyngeal damage induced by MTX.
ABSTRACT
OBJECTIVE:: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. MATERIAL AND METHODS:: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. RESULTS:: The levels of MDA, IL-1ß, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. CONCLUSION:: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.
Subject(s)
Folic Acid Antagonists/adverse effects , Hippophae/chemistry , Methotrexate/adverse effects , Plant Extracts/pharmacology , Stomatitis/chemically induced , Stomatitis/drug therapy , Animals , Blood Vessels/pathology , Cheek/pathology , Gene Expression , Interleukin-1beta/analysis , Interleukin-1beta/drug effects , Lip/pathology , Malondialdehyde/analysis , Plant Extracts/therapeutic use , Rats , Reproducibility of Results , Stomatitis/pathology , Tongue/pathology , Treatment Outcome , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/drug effectsABSTRACT
ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.
Subject(s)
Animals , Rats , Stomatitis/chemically induced , Stomatitis/drug therapy , Plant Extracts/pharmacology , Methotrexate/adverse effects , Hippophae/chemistry , Folic Acid Antagonists/adverse effects , Stomatitis/pathology , Tongue/pathology , Blood Vessels/pathology , Plant Extracts/therapeutic use , Gene Expression , Cheek/pathology , Reproducibility of Results , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/drug effects , Treatment Outcome , Interleukin-1beta/analysis , Interleukin-1beta/drug effects , Lip/pathology , Malondialdehyde/analysisABSTRACT
BACKGROUND: In this study, the effects of levosimendan used in the treatment of acute congestive heart failure upon pulmonary fibrosis in rats induced with bleomycin (BL) were analyzed. METHODS: A total of 33 male Sprague-Dawley type rats were categorized into five groups randomly. About 2.5U/kg BL was intratracheally administered to the rats in the BL, BL+L1, BL+L2, and BL+L3 groups, and 0.9% saline was intratracheally administered at the same rate to the control group. 0.3, 1, and 3mg/kg levosimendan was intraperitoneally administered to the BL+L1, BL+L2, and BL+L3 groups, respectively. Blood and tissue samples were taken from the rats euthanized to determine the changes in erythrocyte enzyme activities and to conduct histopathological evaluations after 14 days. With values between 0 and 3, histopathological scoring damage was assessed by the presence of inflammation and fibrosis in a semiquantitative manner. RESULTS: Compared with those in the C group, glutathione reductase (GR) and Catalase (CAT) enzymes decreased in the BL group; compared with that in the BL group, GR increased in the BL+L1 and BL+L3 groups, 6-phosphogluconate dehydrogenase (6PGD) increased in the BL+L3 group, and CAT increased in the BL+L2 and BL+L3 groups (p<0.05). In the histopathological evaluation, fibrosis occurred in all rats in the BL group, and tissue damage was noticed to be generally less in the BL+L1, BL+L2, and BL+L3 groups (p<0.001). CONCLUSIONS: The results obtained from biochemical and histopathological evaluations indicate that levosimendan had an anti-fibrotic effect without a dose-dependent response on pulmonary fibrosis.
Subject(s)
Bleomycin/pharmacology , Hydrazones/pharmacology , Lung/drug effects , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pyridazines/pharmacology , Animals , Catalase/metabolism , Erythrocytes/drug effects , Erythrocytes/metabolism , Glutathione Reductase/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Lung/metabolism , Male , Phosphogluconate Dehydrogenase/metabolism , Pulmonary Fibrosis/metabolism , Rats , Rats, Sprague-Dawley , SimendanABSTRACT
We aimed to evaluate the effect of melatonin on oxidative stress and ovarian injury in rats. Twenty-four Sprague-Dawley albino rats were divided into three groups: Group 1 as nondiabetic healthy controls (n = 8), group 2 as nontreated diabetic rats (n = 8) and group 3 as melatonin-treated diabetic rats (n = 8). After overt diabetes was produced by intraperitoneal injection of streptozosin, 20 mg/kg/day of melatonin was given intraperitoneally to group 3 for a week. NF-kB and caspase-3 immunoexpressions, lipid peroxidation, the activities of antioxidative enzymes, total oxidant capacity and total antioxidant capacity were assessed. Immunoexpressions of NF-kB and caspase-3 were significantly lower in group 3 than group 2. There was a significant decrease in superoxide dismutase activity in group 2 than group 1 and a significant increase in group 3 compared with group 2. We observed a nonsignificant decrease in catalase activity between group 1 and group 2 and a nonsignificant increase between group 2 and group 3. There was a nonsignificant increase in the plasma level of total oxidant status in group 2 than group 1, but a significant decrease was observed in group 3 compared to group 2. Total antioxidant status was significantly lower in group 2 compared with group 1 and group 3. In conclusion, melatonin ameliorates the negative effects of oxidative stress on DM-related ovarian injury.
Subject(s)
Apoptosis/drug effects , Diabetes Mellitus, Experimental/metabolism , Melatonin/pharmacology , Ovary/drug effects , Oxidative Stress/drug effects , Animals , Apoptosis/physiology , Caspase 3/metabolism , Female , NF-kappa B/metabolism , Ovary/metabolism , Oxidative Stress/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Cholesterol and its biosynthetic pathway intermediates and derivatives are required for many developmental processes including membrane biogenesis, transmembrane receptor signaling, steroid biogenesis, nuclear receptor activation, and posttranslational modification of hedgehog (Hh) proteins. To perform such multifaceted tasks depends on stringent regulation of expression of cholesterol biosynthetic enzymes (CBEs). We established for a whole organism, for the first time, the 3D expression pattern of all genes required for cholesterol biosynthesis (CBS), starting from acetyl-CoA and ending with cholesterol. This data was produced by high-throughput in situ hybridization on serial sections through the mouse fetus. The textually annotated image data were seamlessly integrated into the METscout and GenePaint public databases. This novel information helps in the understanding of why CBEs are expressed at particular locations within the fetus. For example, strong CBE expression is detected at sites of cell proliferation and also where cell growth increases membrane surface, such as in neurons sprouting axons and forming synapses. The CBE data also sheds light on the spatial relationship of cells and tissue that express sonic Hh (Shh) and produce cholesterol, respectively. We discovered that not all cells expressing Shh are capable of CBS. This finding suggests novel ways by which cholesterylation of Shh is regulated.
Subject(s)
Cholesterol/biosynthesis , Embryo, Mammalian/enzymology , Gene Expression Regulation, Developmental , Animals , Embryo, Mammalian/metabolism , Energy Metabolism , MiceABSTRACT
Lactoperoxidase (LPO) catalyzes the oxidation of numerous of organic and inorganic substrates by hydrogen peroxide. It has very vital activity in the innate immune system by decreasing or stopping the activation of the bacteria in milk and mucosal secretions. This study's purpose was to investigate in vitro effect of some phenolic acids (ellagic, gallic, ferulic, caffeic, quercetin, p-coumaric, syringic, catechol and epicatechin) on the purified LPO. This enzyme was purified from milk by using different methods such as Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange and Sephadex G-100 gel filtration chromatography. LPO was purified 28.7-fold with a yield of 20.03%. We found phenolic acids have inhibition effects on bovine LPO enzyme to different concentrations. Our study showed lower concentrations of caffeic acid, ferulic acid and quercetin exhibited much higher inhibitory effect on enzyme, so these three of them were clearly a more potent inhibitor than the others were. All of compounds were non-competitive inhibitors.
Subject(s)
Hydroxybenzoates/pharmacology , Lactoperoxidase/antagonists & inhibitors , Animals , Cattle , Dose-Response Relationship, Drug , Hydroxybenzoates/chemistry , Lactoperoxidase/metabolism , Molecular Structure , Structure-Activity RelationshipABSTRACT
BACKGROUND AND OBJECTIVE: Iron is an essential element that is necessary for all cells in the body. Iron deficiency anemia (IDA) is one of the most common nutritional disorders in both developed and developing countries. The glutathione pathway is paramount to antioxidant defense and glucose-6-phosphate dehydrogenase (G6PD)-deficient cells do not cope well with oxidative damage. The goal of this study was to check the activities of G6PD, 6-phosphogluconate dehydrogenase, glutathione reductase in patients with IDA. METHODS: We analyzed the plasma samples of 102 premenopausal women with IDA and 88 healthy control subjects. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activity as compared to the reduction of NADP +, glutathione reductase activity was performed based on the oxidation of NADPH. 2 ml of plasma were used in all analyzes. SPSS program was used for all of the statistical analysis. RESULT: Diagnosis of iron deficiency in patients belonging to the analysis of blood were ferritin 3.60 ± 2.7 ng / mL, hemoglobin 9.4 ± 1.5 mg / dl and hematocrit 30.7 ± 4.1% ratio; in healthy subjects ferritin 53.5 ± 41.7 ng/ml, hemoglobin level 13.9 ± 1.3 mg / dl and hematocrit ratio 42 ± 3.53%. When compared to healthy subjects the glutathione reductase level (P<0.001) was found to be significantly higher in patients with IDA. IDA patients with moderate and severe anemia had lower GR activity when compared to IDA patients with mild anemia. But the plasma levels of glucose-6-phosphate dehydrogenase (P<0,600) and 6-phosphogluconate dehydrogenase (P<0,671) did not show any differences between healthy subjects and in patients with IDA. CONCLUSION: It was shown that Glucose-6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase have no effect on iron-deficiency anemia in patients. The plasma GR levels of premenopausal women with IDA were found to be higher compared to healthy subjects, which could be secondary to erythrocyte protection against oxidative stress being commonly seen in IDA.
ABSTRACT
Cord blood has numerous facilities for life and used in many different areas. Cord blood contains many different catalytic proteins including antioxidant enzymes. Here we purified human cord blood glutathione reductase (hcbGR), glutathione S-transferase (hcbGST) and human cord blood glutathione peroxidase (hcbGPx) from human cord blood erythrocytes and analyzed the inhibition effects of the antibiotics incorporating cefuroxime, ceftriaxone, ceftizoxime and cefoperazone, on these enzymes. K(I) values for the drugs ranged from 10.42 to 28.72 µM for hcbGR, 32.7 to 244.8 µM for hcbGPx, and 32.39 to 267.3 µM for hcbGST. Cefuroxime caused the highest inhibition on all enzymes with KI values of 10.42, 32.39, 32.7 µM for hcbGR, hcbGST, and hcbGPx, respectively. All drugs displayed non-competitive inhibition regardless of their structures. Since these drugs are often used during pregnancy, identification of possible undesired impacts on various parameters has a great importance for pharmacological and medical applications.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/metabolism , Glutathione Peroxidase/antagonists & inhibitors , Glutathione Reductase/antagonists & inhibitors , Glutathione Transferase/antagonists & inhibitors , Anti-Bacterial Agents/chemistry , Cefoperazone/chemistry , Cefoperazone/pharmacology , Ceftizoxime/chemistry , Ceftizoxime/pharmacology , Ceftriaxone/chemistry , Ceftriaxone/pharmacology , Cefuroxime/chemistry , Cefuroxime/pharmacology , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Erythrocytes/enzymology , Erythrocytes/metabolism , Glutathione Peroxidase/blood , Glutathione Peroxidase/metabolism , Glutathione Reductase/blood , Glutathione Reductase/metabolism , Glutathione Transferase/blood , Glutathione Transferase/metabolism , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that catalyze the hydration of CO(2) to bicarbonate and protons. Inhibition of CAs has been clinically exploited for the treatment of various classes of diseases for decades, but investigating new classes of inhibitors continues to be important. We have synthesized a series of 2-amino-3-cyano-4-heteroaryl (5a-l) compounds and characterized the structures by NMR, IR and elemental analyses. We tested the ability of these compounds to inhibit two metalloenzyme human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and hCA II. Compounds 5d and 5b showed the best inhibition activity against hCA I (IC(50): 33 and 34 µM, respectively), and compound 5d showed the best activity against hCA II (IC(50): 56 µM).