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Toll-like receptor 4 (TLR-4) ligands were initially shown to be the source of lipopolysaccharide (LPS), a gram-negative bacterium's cell wall immunostimulatory component. Oxidative stress, apoptosis, and inflammation are all potential effects of LPS treatment on the lungs. By triggering oxidative stress and inflammation, these negative effects could be avoided. Robust flavonoid oleuropein (OLE) exhibits anti-inflammatory, antiproliferative, and antioxidative properties. A nanodelivery system could improve its low bioavailability, making it more effective and useful in treating chronic human ailments. This study evaluates the effects of AgNP-loaded OLE on LPS-induced lung injury in rats in terms of TLR4/P2X7 receptor-mediated inflammation and apoptosis. Forty-eight male albino rats were randomly divided into eight groups. Drugs were administered to the groups in the doses specified as follows: Control, LPS (8 mg/kg ip), OLE (50 mg/kg) AgNPs (100 mg/kg), OLE + AgNPs (50 mg/kg), LPS + OLE (oleuropein 50 mg/kg ig + LPS 8 mg/kg ip), LPS + AgNPs (AgNPs 100 mg/kg ig + LPS 8 mg/kg ip), and LPS + OLE + AgNPs (OLE + AgNPs 50 mg/kg + LPS 8 mg/kg ip). After the applications, the rats were decapitated under appropriate conditions, and lung tissues were obtained. Oxidative stress (SOD, MDA, and GSH), and inflammation (IL-6, IL-1ß, TNF-α, Nrf2, P2X7R, AKT, and TLR4) parameters were evaluated in the obtained lung tissues. Additionally, histopathology studies were performed on lung tissue samples. The data obtained were evaluated by comparison between groups. Both OLE and OLE + AgNPs showed potential in reducing oxidative stress, inflammation, and apoptosis (p < 0.05). These findings were supported by histopathological analysis, which revealed that tissue damage was reduced in OLE and OLE + AgNPs-treated groups. According to the results, LPS-induced lung injury can be reduced by using nanotechnology and producing OLE + AgNP.
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BACKGROUND: Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin. METHODS: Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5 mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100 mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1 ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100 mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant. RESULTS: As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05). CONCLUSION: Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties.
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Apoptose , Mucosa Gástrica , Indometacina , Inflamação , Estresse Oxidativo , Probióticos , Úlcera Gástrica , Indometacina/efeitos adversos , Probióticos/farmacologia , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Úlcera Gástrica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ratos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Inflamação/metabolismo , Masculino , Ratos Wistar , Antioxidantes/metabolismo , Antioxidantes/farmacologiaRESUMO
Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.
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Proliferação de Células , Ouro , Nanopartículas Metálicas , Metformina , Humanos , Metformina/farmacologia , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Células A549 , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems. Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats. Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group. Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress. The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.
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Apoptose , Doxorrubicina , Estresse do Retículo Endoplasmático , Glucosídeos Iridoides , Iridoides , Nanopartículas Metálicas , Prata , Testículo , Animais , Masculino , Glucosídeos Iridoides/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Ratos , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Iridoides/farmacologia , Iridoides/química , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologiaRESUMO
This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1ß levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.
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Selênio , Testículo , Ratos , Masculino , Animais , Selênio/farmacologia , Di-Hidrotestosterona/metabolismo , Di-Hidrotestosterona/farmacologia , Acrilamida , Motilidade dos Espermatozoides , Estresse Oxidativo , Antioxidantes/metabolismo , Inflamação/metabolismo , Hormônio Foliculoestimulante/metabolismo , Apoptose , Dano ao DNA , AutofagiaRESUMO
Cerebral ischemia and reperfusion are related to various situations like injuries after various traumas, oxidative stress, increased calcium ion, capillary hypoperfusion, microvascular hyperpermeability, leukocyte infiltration, and blood-brain barrier disruption. An antidepressant Agomelatine which is a melatonin receptor (MT1/MT2) agonist and serotonin receptor (5-HT2C) antagonist has been reported by studies to have antioxidant and anti-inflammatory effects. In our study, we aimed to detect the effects of citrate-coated silver nanoparticle-loaded agomelatine application on neurodegeneration, endoplasmic reticulum stress, autophagic and apoptotic cell death, inflammation, and P2X7R expression in the cerebral ischemia-reperfusion model to facilitate the passage of blood-brain barrier. Forty two Sprague-Dawley rats in total were divided into six equal groups (n:7) and applications were performed. Acute cerebral injury in the ischemia-reperfusion model was created 2 h after internal carotid artery ligation in rats and then at the 2nd hour of reperfusion citrate-coated silver nanoparticles loaded with Agomelatine were applied. Twenty four hours later, neurologic analysis on animals in experimental groups was performed, animals were decapitated and GSH, GPx, SOD, CAT, MDA, IL-1ß, and TNF-α parameters were examined after taking blood and the cerebral tissue samples. As a result, it was determined that ischemia-reperfusion caused endoplasmic reticulum stress in the cerebral tissues and thus caused cellular injury.
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Isquemia Encefálica , Nanopartículas Metálicas , Traumatismo por Reperfusão , Ratos , Animais , Ratos Sprague-Dawley , Inflamassomos/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Prata , Ácido Cítrico/farmacologia , Traumatismo por Reperfusão/metabolismo , Estresse Oxidativo , Isquemia Encefálica/metabolismo , Citratos/farmacologia , Reperfusão , Isquemia , Estresse do Retículo EndoplasmáticoRESUMO
Objectives: Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats. Materials and Methods: In this study, 50 adult male Sprague Dawley rats weighing approximately 200-250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed. Results: CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-ß, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). Conclusion: The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats.
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Acrylamide (ACR) is used in many fields such as cosmetics, paper, and textile industries. It also occurs at very high temperatures in some foods. Gonadotoxic effects of ACR have been found in experimental animals. Many studies use flavonoids to prevent the reproductive side effects of ACR. Naringin (NA) is a flavonoid and it has been determined by studies that it has no toxic effect on tissues. In our study, we aimed to determine the protective effect of NA against the damage of ACR on testicular tissue and the reproductive system in rats. In our study, 50 Spraque Dawley male rats weighing 220-250 grams were used. Control: Only intragastric saline was administered for 10 days. ACR: Animals received ACR (40 mg/kg, intraperitoneally) for 10 days. NA50+ACR: Animals were given NA for 10 days and each NA was one hour after the administration of ACR. NA100+ACR: Animals received NA for 10 days and one hour after each NA was given ACR. NA100: Animals were given NA for 10 days. At the end of the applications, the rats were euthanized by cervical dislocation under anesthesia. Serum FSH, LH, and Dihydrotestosterone levels were compared between the groups. In addition, oxidative stress, inflammation, expression of some reproductive enzymes, and apoptosis markers were determined in testicular tissues. When these parameters were compared between groups, ACR induced testicular dysfunction and tissue damage in rats. We determined that only the NA application did not cause tissue damage. and the administration of NA along with ACR significantly reduced ACR-induced testis toxicity.
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Acrilamida , Testículo , Animais , Masculino , Ratos , Acrilamida/toxicidade , Apoptose , Flavonoides/farmacologia , Inflamação , Estresse Oxidativo , Antioxidantes/farmacologia , Reprodução/efeitos dos fármacosRESUMO
Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)-treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU-induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU-induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU-induced nephrotoxicity.
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Curcumina , Hesperidina , Insuficiência Renal , Animais , Antioxidantes/metabolismo , Curcumina/metabolismo , Curcumina/farmacologia , Fluoruracila/toxicidade , Glutationa/metabolismo , Hesperidina/farmacologia , Humanos , Rim/metabolismo , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo , Superóxido Dismutase/metabolismoRESUMO
We sought to determine the effects of selenium (Se) on acrylamide (ACR)-induced nephrotoxicity in rats. In our study, 50 adult male Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups. The control group was given intra-gastric (i.g.) saline (1 mL) for 10 days. The ACR group was given i.g. ACR in saline (38.27 mg/kg titrated to 1 mL) for 10 days. The Se0.5 + ACR and Se1 + ACR groups were administered Se in saline (0.5 and 1 mg/kg, respectively) for 10 days and given i.g. ACR (38.27 mg/kg) one hour after the Se injections. The Se1 group was administered i.g. Se (1 mg/kg) for 10 days. On day 11, intracardiac blood samples were obtained from the rats while they were under anesthesia, after which they were euthanized by decapitation. Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer. Enzyme-linked immunosorbence immunosorbent assay (ELISA) was used to quantify malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB), interleukin (IL)-33, IL-6, IL-1ß, cyclooxygenase-2 (COX-2), kidney injury molecule-1 (KIM-1), mitogen-activated protein kinase-1 (MAPK-1), and caspase-3 in kidney tissues. Renal tissues were evaluated by histopathological and immunohistochemical examinations for 8-hydroxylo-2'-deoxyguanosin 8-hydroxy-2'-deoxyguanosine (8-OhDG) and Bax. Serum urea and creatinine levels were higher in the ACR group than in the control, and these ACR-induced increases were prevented by high doses of Se. Additionally, ACR induced the renal oxidative stress, inflammation, apoptosis, and damage to DNA and tissue; likewise, these were prevented by high doses of Se. Taken with ACR, Se confers protection against ACR-induced nephrotoxicity in rats by reducing oxidative stress, inflammation, apoptosis, and DNA damage.
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Selênio , Acrilamida/toxicidade , Animais , Apoptose , Dano ao DNA , Glutationa/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Rim/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Selênio/metabolismo , Selênio/farmacologiaRESUMO
Aim: The objective of this study was to evaluate the possible protective effects of probiotic bacteria, especially Bifidobacterium and Lactobacillus strains, on 4,4'-dichlorodiphenyltrichloroethane (DDT)-induced toxicity. For this reason, we evaluated the relationship between probiotics and toxicity by checking immunological and immunohistochemical parameters. Materials & methods: Probiotic pretreatment was applied to 36 Wistar albino rats for 12 consecutive days. Serum aspartate aminotransferase and alanine aminotransferase levels were detected. CD3 and NF-κB staining methods were then performed by immunohistochemistry. Finally, pro- and anti-inflammatory cytokines were measured by ELISA. Results: DDT caused a serious increase/decrease in some cytokine parameters. The effective dose was 1 × 1011 colony-forming unit probiotic treatment. CD3 and NF-κB positivity were intense in DDT group whereas the intensity was reduced in probiotic treatment groups. Discussion: The probiotic mixture has a potential to prevent inflammatory and oxidative stress related organ injuries. Further studies should be performed to explain the possible mechanisms.
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Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citocinas/sangue , DDT/toxicidade , Probióticos , Baço/efeitos dos fármacos , Animais , Bifidobacterium , Complexo CD3/análise , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Inflamação/prevenção & controle , Lactobacillus , Fígado/química , Fígado/efeitos dos fármacos , Fígado/imunologia , NF-kappa B/análise , Estresse Oxidativo , Ratos , Ratos Wistar , Baço/química , Baço/imunologiaRESUMO
OBJECTIVES: 5-fluorouracil-induced (5-FU), an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity. MATERIALS AND METHODS: Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringin+5-FU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken. RESULTS: It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringin+5-FU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringin+5-FU groups. CONCLUSION: Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage.
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Type II diabetes is known to cause neuropathy, nephropathy and retinopathy. However, cardiovascular disorders associated with diabetes have been ignored. In traditional medicine, cinnamon (Cinnamomum cassia) bark has been used for its abilities to relieve fever, inflammation and chronic bronchitis. In the present study, the effect of Cinnamomum cassia extract (CN) on the thoracic aorta in an experimental type II diabetes model was investigated. In rats administered with nicotinamide + streptozotocin, significant endothelial dysfunction and oxidative stress were characterised by increased inducible nitric oxide synthase (iNOS) and decreased insulin/proinsulin levels. This impairment was prevented by administering 1000 mg/kg metformin or 500-1000-1500 mg/kg CN. CN administration attenuated the inflammatory response by decreasing the levels of malondialdehyde (MDA), Nitric oxide (NO) and increasing Glutathione peroxidase (GPx), glutathione (GSH). In addition, CN administration was shown to cause down-regulating effects on iNOS in thoracic aorta. These findings reveal that CN could prevent chronic complications of experimentally induced type II diabetes by attenuating inflammation, oxidant/antioxidant imbalance, and normalised contraction and relaxion responses in the thoracic aorta.
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Animais , Feminino , Ratos , Estresse Oxidativo , Cinnamomum aromaticum/efeitos adversos , Extratos Vegetais/classificação , Anormalidades Cardiovasculares , Diabetes Mellitus Tipo 2/induzido quimicamenteRESUMO
Cyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP's side effects. This study aimed to investigate the protective effect of quercetin (QUE) on CYP-induced lung toxicity in rats using histologic and biochemical methods. In the study, 50 male Sprague-Dawley rats weighing 220-250g were used. There were 4 experimental groups and 1 control group. Group I is the control group, which was given only intragastric (i.g.) solvent (corn oil) for 7days. Group II was given i.g. corn oil for 7days as a placebo, and a single dose of intraperitoneal (i.p.) CYP (200mg/kg) was given on day 7. Groups III and IV, respectively, were given QUE in doses of 50 and 100mg/kg, dissolved in corn oil, and administered i.g. for 7days. In addition, a single dose of CYP (200mg/kg, i.p.) was administered on the 7th day of study. In Group V, a 100mg/kg dose of QUE was given to rats i.g. for 7days. On the 8th day of the experiment, all groups of rats' blood and lung tissue samples were collected for analysis of oxidative stress parameters and histopathological examinations. In the biochemical result (although oxidative parameters were increased in favor of tissue damage) QUE administration revealed attenuated CYP toxicity in the rats 'lungs. In histologic analysis, QUE prevented the CYP-mediated tissue damage and the increase in mast-cell densities in the rats' lung tissues. The results of the present study have revealed that QUE provides a possible protective effect by inhibiting ROS and mast cell degranulation in induced lung damage.
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Ciclofosfamida/toxicidade , Citoproteção/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Quercetina/farmacologia , Animais , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/toxicidade , Antioxidantes/farmacologia , Citoproteção/fisiologia , Pulmão/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Probiotics are "live", beneficial microbes that provide important health benefits in their hosts. There is significant interest in the modulation and regulation of the immune function by probiotics. OBJECTIVE: To investigate the immunomodulatory effects of a probiotic mixture, including Lactobacillus and Bifidobacterium species, by detecting serum cytokine and immunoglobulin levels. METHODS: The rats were randomly divided into 4 groups. The first group was "Control group" and other 3 groups were probiotic application groups who received different doses of probiotics. The probiotic mixture included 12 probiotic bacteria, mostly Lactobacillus and Bifidobacterium strains. Probiotic mixture was administered to rats for 12 consecutive days. TNF-α, TGF-ß, IL-1-ß, IL-6, and IL-10 levels as well as serum IgG and IgA concentrations were detected in the sera after 12 days. RESULTS: Probiotics led to a decrease in the levels of TNF-α, IL-6 and TGF-ß; however, they led to increase in the serum levels of IL-10, IgG and IgA. There were significant differences between control group and probiotic application groups (p<0.05). CONCLUSION: These data suggest that the commensal microbiota are important for stimulating both proinflammatory and regulatory responses in order to rapidly clear infections and minimize inflammation-associated tissue damage.
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Bifidobacterium/imunologia , Lactobacillus/imunologia , Probióticos/metabolismo , Animais , Citocinas/sangue , Feminino , Homeostase , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunomodulação , Ratos , Ratos WistarRESUMO
OBJECTIVES: In the present study, our aim was to investigate the possible protective effects of epigallocatechin gallate (EGCG) on lipopolysaccharide (LPS)-induced hepatotoxicity by using Hep3B human hepatoma cells. Specifically, the study examines the role of some proinflammatory markers and oxidative damage as possible mechanisms of LPS-associated cytotoxicity. Consequently, the hepatocellular carcinoma cell line Hep3B was chosen as a model for investigation of LPS toxicity and the effect of EGCG on LPS-exposed cells. MATERIALS AND METHODS: The Hep3B human hepatoma cells were used for this study. The cytotoxic effects of chemicals (EGCG and LPS), AST and ALT levels, SOD and CAT activities, GSH-Px level and TNF-alpha and IL-6 levels were detected by using different biochemical and molecular methods. LPS and EGCG were applied to cells at various times and doses. RESULTS: The highest treatment dose of EGCG (400 µM) led to a dramatic decrease in SOD level and increase in CAT and GSH levels. Additionally, the highest dose of EGCG also led to a dramatic increase in TNF-alpha and IL-6 levels. On the other hand, effective doses of EGCG (200 and 100 µM) normalized all related parameters levels. CONCLUSION: LPS caused hepatotoxicity, but interestingly, a high dose of EGCG was found to be a cytotoxic agent in this study. However, other two doses of EGCG led to a decrease in both inflammatory cytokine levels and antioxidant enzyme levels. Further studies should examine the effect of EGCG on secondary cellular signaling pathways.
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Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment.