RESUMO
Purpose: Favipiravir (FAV) used against COVID-19 is an antiviral drug that causes adverse reactions, such as hyperuricaemia, liver damage, and hematopoetic toxicity. The aim of the study was to investigate the systemic and ocular side-effects of FAV in rats, for the first time.Materials and methods: A total of 18 albino male Wistar rats were used in the study. The rats were divided into 3 groups as the healthy group (HG), the group given 50 mg/kg/day favipiravir (FAV50), and the group given 200 mg/kg/d favipiravir (FAV200). These doses were given to the experimental groups for one week. At the end of the experiment histopathological examinations were performed on the conjunctiva and sclera of the eye. In addition, malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-α) levels were measured in blood samples taken from rats. Results: Compared to HG, the MDA (1.37 ± 0.61 vs. 4.82 ± 1.40 µmol/mL), IL-1ß (2.52 ± 1.14 vs. 6.67 ± 1.99 pg/mL), and TNF-α levels (3.28 ± 1.42 vs. 8.53 ± 3.06 pg/mL) of the FAV200 group were higher. The levels of tGSH (7.58 ± 1.98 vs. 2.50 ± 0.98 nmol/mL) and SOD (13.63 ± 3.43 vs. 3.81 ± 1.43 U/mL) the FAV200 group were lower than the HG (p < 0.05, for all). The degree of damage to the cornea and sclera of the FAV200 group was quite high according to HG (p < 0.001). Conclusions: FAV can cause damage to rat conjunctiva and sclera by increasing oxidant stress and inflammation at high dose.
Assuntos
Amidas , Antivirais , Pirazinas , Ratos Wistar , Animais , Masculino , Pirazinas/toxicidade , Pirazinas/administração & dosagem , Amidas/toxicidade , Ratos , Antivirais/toxicidade , Glutationa/metabolismo , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Olho/efeitos dos fármacos , Olho/patologia , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Interleucina-1beta/sangue , Túnica Conjuntiva/patologia , Túnica Conjuntiva/efeitos dos fármacosRESUMO
The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.
Assuntos
Ovário , Traumatismo por Reperfusão , Feminino , Ratos , Animais , Ovário/metabolismo , alfa-Metiltirosina/metabolismo , alfa-Metiltirosina/farmacologia , Ratos Wistar , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Isquemia/metabolismo , Isquemia/patologia , Glutationa , Reperfusão , Superóxido Dismutase/metabolismo , Estresse OxidativoRESUMO
Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1ß, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.
Assuntos
Doenças Ovarianas , Traumatismo por Reperfusão , Animais , Humanos , Ratos , Feminino , Doenças Ovarianas/tratamento farmacológico , Doenças Ovarianas/prevenção & controle , Doenças Ovarianas/complicações , Torção Ovariana/complicações , Ratos Wistar , Isquemia/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/etiologia , Reperfusão/efeitos adversos , Antioxidantes/farmacologiaRESUMO
The role of oxidants and proinflammatory cytokines in the pathogenesis of pneumonia caused by Staphylococcus aureus (S. aureus) has been demonstrated. The present study aims to investigate the protective effect of ethyl acetate extract (EtOAc) obtained from Usnea longissima (UL) against acute oxidative and inflammatory lung damage due to S. aureus infection in rats. Albino Wistar-type male rats were divided into three groups: Healthy (HG), S. aureus inoculated (SaG), and S. aureus inoculated + ULEtOAc administered (SUL). SaG (n = 6) and SUL (n = 6) group rats' left nostrils (excluding HG) were inoculated with 0.1 ml bacterial mixture. After 24 hours, ULEtOAc (50 mg/kg) was administered orally to the SUL group, and the same volume of normal saline was administered orally to the HG (n = 6) and SaG groups. This procedure was performed once a day for seven days. Levels of oxidant and antioxidant parameters such as malondialdehyde (MDA) and total glutathione (tGSH), as well as pro-inflammatory cytokine levels such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1ß), were measured in removed lung tissues. Tissues were also examined histopathologically. Biochemical results showed that ULEtOAc significantly suppressed the increase of MDA, NF-κB, TNF-α, and IL-1ß levels and the decrease of tGSH caused by S. aureus in lung tissue. S. aureus inoculation caused severe mononuclear cell infiltration in interstitial areas, severe lymphoid hyperplasia in bronchial-associated lymphoid tissue and severe alveolar edema, histopathologically. Treatment with ULEtOAc had an attenuating effect on these histopathological findings. Experimental results from this study suggest that ULEtOAc may be beneficial in treating S. aureus-induced oxidative and inflammatory lung damage.
Assuntos
Pneumonia , Infecções Estafilocócicas , Ratos , Masculino , Animais , Staphylococcus aureus/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , NF-kappa B/metabolismo , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Glutationa/metabolismo , Glutationa/farmacologia , Ratos Wistar , Pulmão/metabolismo , Pulmão/patologia , Citocinas , Estresse Oxidativo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologiaRESUMO
Background and Objectives: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. Materials and Methods: The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. Results: In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. Conclusions: The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.
Assuntos
Epilepsia , Meperidina , Ratos , Animais , Meperidina/efeitos adversos , Epinefrina/uso terapêutico , Norepinefrina , Hidrocortisona , Metirapona , Cafeína/efeitos adversos , Analgésicos , ConvulsõesRESUMO
Current study aimed to research the effect of Hippophae rhamnoides (HRE) on potantial oral oxidative and inflammatory damage of 5-FU in rats. The rats were assigned to three groups; healthy (HG), 5-FU 100mg/kg (FUG) and HRE 50mg/kg +5-FU 100mg/kg (HRFU). The 5-FU was injected in the FUG group intraperitoneally. The HRFU was injected 5-FU at 100mg/kg IP one hour after the 50mg/kg HRE was given orally. Olive oil was used as a solvent for the HG. HRE was given to the rats three times a day for ten days. 5-FU was given one dose on the 1st, 3rd and 5th days. On the 10th day, the tissues removed from the animals were euthanized with high-dose anaesthesia and were macroscopically examined. The levels of the oxidant, antioxidant and proinflammatory cytokines were investigated.It was seen that HRE alleviated the symptoms of severe mucositis by antagonizing the effects of 5-FU on oxidant, antioxidant and proinflammatory cytokines such as malondialdehyde, total glutathione, superoxide dismutase, catalase, nuclear factor kappa-B and interleukin-6 in inner cheek and tongue tissue. These results recommend that HRE may be benefical in the cure of 5-FU-associated oral mucositis.
Assuntos
Hippophae , Estomatite , Ratos , Animais , Fluoruracila/toxicidade , Antioxidantes/farmacologia , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Interleucina-6 , Oxidantes/farmacologia , Mucosa IntestinalRESUMO
Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.
Assuntos
Edema , Indometacina , Animais , Anti-Inflamatórios/farmacologia , Carragenina/uso terapêutico , Carragenina/toxicidade , Ciclo-Oxigenase 2/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Flavonoides , Glutationa , Indometacina/farmacologia , Masculino , Malondialdeído , Extratos Vegetais , Ratos , Ratos WistarRESUMO
PURPOSE: Bevacizumab is a recombinant humanized monoclonal antibody that specifically binds to vascular endothelial growth factor (VEGF). Cutaneous side effects of bevacizumab are seen with substantial frequency and may require the interruption of the treatment. The aim of the study was to conduct a biochemical and histopathological investigation of the effects of carvacrol against the possible oxidative skin damage caused by bevacizumab in rats. MATERIALS AND METHODS: A total of 18 adult male Wistar albino rats were randomly assigned to three groups as healthy (H group; n = 6), bevacizumab alone (B group; n = 6), and carvacrol + bevacizumab (CB group; n = 6). Carvacrol was injected intraperitoneally (IP) at a dose of 50 mg/kg in the CB group. Sterile salt solution (0.9% NaCl) was used as a solvent for the H and B groups. One hour after the administration of carvacrol and solvent, bevacizumab at a dose of 10 mg/kg IP was administered to the CB and B groups. Bevacizumab was given once daily for a total of two doses, 15 days apart. Carvacrol was administered once daily for one month. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPO), catalase (CAT), superoxide dismutase (SOD), total oxidant status (TOS), and total antioxidant status (TAS) levels in rats' skin tissues were biochemically evaluated. The parameters were measured with spectrophotometric method by using a microplate reader (BioTek, Winooski, VT, USA). The skin tissues were also examined histopathologically by the pathologist (blind) for the study groups. RESULTS: The MDA and TOS levels of the H and CB groups were significantly lower than the B group (p < 0.05). The mean scores of the other biochemical levels (GSH, GPO, CAT, SOD, TAS) in the H group were significantly higher than in the B and CB groups. Pathological examination of H group was normal. In B group epidermal atrophy, abnormal keratin accumulation, degenerated hair follicles, edoema and inflammatory cells accumulation in the dermis were observed. In the CB group, these findings were significantly improved. CONCLUSION: The positive effect of carvacrol against possible local oxidative skin damage due to bevacizumab in rats was demonstrated. In addition, more detailed studies are required to clarify the mechanism of the protective effect of carvacrol against bevacizumab-induced skin toxicity. The effect should be evaluated through further human studies, as well as studies using different doses of carvacrol.
Assuntos
Bevacizumab , Cimenos , Estresse Oxidativo , Dermatopatias , Superóxido Dismutase , Fator A de Crescimento do Endotélio Vascular , Animais , Masculino , Ratos , Antioxidantes/metabolismo , Bevacizumab/efeitos adversos , Glutationa/metabolismo , Malondialdeído/metabolismo , Oxidantes , Ratos Wistar , Solventes , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cimenos/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Dermatopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , TimolRESUMO
AIM: In this study, it was aimed to investigate the effect of coenzyme Q10 (CoQ10) on cisplatin-induced oxidative retinal damage in rats biochemically and histopathologically. MATERIALS AND METHODS: Thirty male Wistar albino rats were divided into 3 groups randomly: untreated control (C group), only 2.5 mg/kg cisplatin daily administrated group for 2 weeks (CP group), 2.5 mg/kg cisplatin + 20 mg/kg orally CoQ10 daily administrated group for 2 weeks (CoQC group). At the end of experimental period, blood samples obtained before sacrification for the biochemical examination of serum malondialdehyde (MDA), total glutathione (tGSH), total oxidant system (TOS), total antioxidant systemic (TAS) levels and after eyes were removed for examined histopathology. RESULTS: As a result of our study, severe histopathological damage was detected in the retinal tissue of the cisplatin group with serum malondialdehyde (MDA) and total oxidant system (TOS) levels were high and total glutathione (tGSH) and total antioxidant systemic (TAS) levels were low. However, it was observed that the histopathological damage associated with cisplatin was decreased in the retinal tissue of the CoQ10 group, which inhibited the increase in blood serum MDA/TOS levels and decrease in tGSH/TAS levels. CONCLUSION: The biochemical and histopathological results of our study were compatible with each other, so we concluded that the damage to the rat retinal tissue caused by cisplatin may be reversible with coenzyme.
Assuntos
Antioxidantes/administração & dosagem , Cisplatino/efeitos adversos , Retina/efeitos dos fármacos , Doenças Retinianas/tratamento farmacológico , Ubiquinona/análogos & derivados , Administração Oral , Animais , Modelos Animais de Doenças , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Retina/patologia , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/patologia , Ubiquinona/administração & dosagemRESUMO
AIM: To investigate the effect of taxifolin on cisplatin-induced oxidative and proinflammatory optic nerve damage in rats. METHODS: A total of 18 albino Wistar male rats were assigned into 3 groups, as follows; Group 1: Control group, Group 2: Only cisplatin administered group for 14 days (Cisplatin group), and Group 3: Taxifolin + cisplatin administered group for 14 days (CIS + TAX group). Serum malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-ÆB), Total Oxidative Status (TOS) and Total Antioxidant Status (TAS) levels were collected from the left eyes of rats. Rats' right eyes were enucleated for histopathological evaluations of optic nerves. RESULTS: NF-ÆB, MDA and TOS levels were statistically significantly higher (p < 0.001) in cisplatin group when compared to other 2 groups, the tGSH and TAS levels of which were statistically significantly lower (p < 0.001). Regarding these parameters, in cisplatin group NF-ÆB, MDA and TOS levels were statistically significantly increased with cisplatin administration and giving taxifolin concomitantly with cisplatin prevented this elevation. On the other hand, tGSH and TAS levels were statistically significantly decreased with cisplatin administration and routine simultaneous application of taxifolin with cisplatin prevented this decrease. In histopathological findings, haemorrhage was observed in the perineum of the injured optic nerves in the cisplatin treated group. And also edoema and degeneration in nerve fascicles in damaged optic nerves were seen in the cisplatin group. In the taxifolin treated group histopathological examinations were close to normal appearance, except mild edoema in nerve fascicles. CONCLUSION: Cisplatin causes oxidative stress on the rat optic nerves, and these changes lead to significant histopathological damage. Taxifolin, which we used to prevent oxidative damage to the optic nerves caused by cisplatin, has been emphasized as a powerful antioxidant agent in many previous scientific investigations. Concomitant administration of taxifolin may prevent these adverse effects of cisplatin, as well as histopathological damage. Further studies are needed to fully determine the effects of cisplatin and taxifolin on the eye.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Cisplatino/efeitos adversos , Doenças do Nervo Óptico/tratamento farmacológico , Nervo Óptico/efeitos dos fármacos , Quercetina/análogos & derivados , Animais , Modelos Animais de Doenças , Masculino , Nervo Óptico/patologia , Doenças do Nervo Óptico/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Quercetina/administração & dosagem , RatosRESUMO
Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Citarabina/efeitos adversos , Edema Pulmonar/tratamento farmacológico , Rutina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Masculino , NF-kappa B/análise , Oxidantes/sangue , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , Ratos , Ratos Wistar , Rutina/farmacologia , Fator de Necrose Tumoral alfa/análiseRESUMO
PURPOSE: Vandetanib is a wide spectrum tyrosine kinase inhibitor used for the treatment of metastatic medullary thyroid cancer (MTC) and various other cancer types. Although it is usually well-tolerated it has been linked to a variety of severe dermatologic reactions. Our study aimed was to investigate adenosine 5'-triphosphate (ATP) on vandetanib-induced skin damage. MATERIALS AND METHODS: A total number of 18 rats were divided into three equal groups as vandetanib group (VDB), vandetanib plus ATP group (VAT), and healthy group (HG); 25 mg/kg ATP was injected intraperitoneally (ip) to the VAT group. Normal saline was given to the HG and VDB groups as solvent via intraperitoneally. One hour later, 25 mg/kg vandetanib was applied orally via an orogastric catheter in the VAT and VDB groups. This procedure was repeated once daily for 4 weeks. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS) levels in rats' skin tissues were evaluated with histopathological analyses. RESULTS: MDA and TOS levels measured higher in the VDB group compared to the VAT and HG groups (p < 0.001). tGSH and TAS levels of the VDB group measured lower than the VAT and HG groups (p < 0.001). The structure and morphology of skin tissue were normal in the control group. In the VDB group, skin tissue damage with thinner epitelium, ruptured and degenerated hair follicles, abnormal accumulation of abnormal keratin on the epithelium and oedematous areas in the dermis was observed. In the VAT group, these findings were significantly improved. CONCLUSION: We demonstrated that adenosine triphosphate can prevent vandetanib-induced skin toxicity in rats for the first time. The promising results denote that further studies testing this agent in other animal models and in humans are warranted.
Assuntos
Trifosfato de Adenosina/uso terapêutico , Antineoplásicos/efeitos adversos , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , Trifosfato de Adenosina/farmacologia , Animais , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Dermatopatias/metabolismo , Dermatopatias/patologiaRESUMO
The objective of this study is to investigate the effects of nimesulide on ketamine-induced ovarian and uterine toxicity by biochemical and histopathological examinations. Ketamine is an anesthetic agent whose use leads to overproduction of catecholamines. Nimesulide is a cyclooxygenase-2 inhibitor, which has also been reported to exert a significant antioxidant effect. Wistar albino female rats were randomly divided into three groups as follows: ketamine group (60 mg/kg), ketamine (60 mg/kg) + nimesulide (50 mg/kg) group, and a healthy control group. Then, the biochemical levels and histopathological findings in the ovaries and uteri of the rats were examined for malondialdehyde, myeloperoxidase, total glutathione and superoxide dismutase. The study demonstrated that, in the uterine and ovarian tissues of rats that have been administered ketamine, there was a decrease in the levels of total glutathione and superoxide dismutase, while malondialdehyde and myeloperoxidase was increased: however it was observed that these ratios were reversed in the ketamine+nimesulide group. It was also proved that the negative effects of ketamine can be corrected with nimesulide when the myometrial and endometrial thicknesses are compared. Antioxidants such as nimesulide may protect against the damage caused by ketamine to the genital organs in young women.
Assuntos
Antioxidantes/farmacologia , Ketamina/efeitos adversos , Ketamina/antagonistas & inibidores , Ovário/efeitos dos fármacos , Sulfonamidas/farmacologia , Útero/efeitos dos fármacos , Animais , Feminino , Glutationa/metabolismo , Malondialdeído/metabolismo , Ovário/enzimologia , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Útero/enzimologia , Útero/metabolismoRESUMO
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.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Quercetina/análogos & derivados , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/sangue , Retinopatia Diabética/patologia , Glutationa/sangue , Interleucina-1beta/sangue , Masculino , Malondialdeído/sangue , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos Wistar , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Fator de Necrose Tumoral alfa/sangueRESUMO
The aim of this study was to investigate the effect of thiamine pyrophosphate (TPP), administered via sugar water, on retinal neovascularisation in rats. Animals were assigned to three groups, namely the TPP sugar-water group (TPSWG, n = 12), the control group (CG, n = 12) and the healthy group (HG, n = 12). The TPSWG was injected intraperitoneally with TPP once a day for 6 months. CG and HG rats were given distilled water in the same way. TPSWG and CG rats were left free to access an additional 0.292 mmol /ml of sugar water for 6 months. The fasting blood glucose (FBG) levels of the animals were measured monthly. After 6 months, biochemical, gene expression and histopathologic analyses were carried out in the retinal tissues removed from the animals after they were killed. The measured FBG levels were 6.96 ± 0.09 mmol/ml (p < 0.0001 vs. HG), 6.95 ± 0.06 mmol/ml (p < 0.0001 vs. HG) and 3.94 ± 0.10 mmol/ml in the CG, TPSWG and HG groups, respectively. The malondialdehyde (MDA) levels were found to be 2.82 ± 0.23 (p < 0.0001 vs. HG), 1.40 ± 0.32 (p < 0.0001 vs. HG) and 1.66 ± 0.17 in the CG, TPSWG and HG, respectively. Interleukin 1 beta (IL-1ß) gene expression was increased (3.78 ± 0.29, p < 0.0001) and total glutathione (tGSH) was decreased (1.32 ± 0.25, p < 0.0001) in the retinal tissue of CG compared with TPSWG (1.92 ± 0.29 and 3.18 ± 0.46, respectively). Increased vascularisation and oedema were observed in the retinal tissue of CG, while the retinal tissues of TPSWG and HG rats had a normal histopathological appearance. A carbohydrate-rich diet may lead to pathological changes in the retina even in nondiabetics, but this may be overcome by TPP administration.
Assuntos
Neovascularização Retiniana , Açúcares/metabolismo , Tiamina Pirofosfato/farmacologia , Tiamina , Animais , Ratos , Ratos Sprague-DawleyRESUMO
Etoricoxib features antioxidant and anti-inflammatory properties concomitantly, suggesting that it may be beneficial in testicular ischemia reperfusion (I/R) damage. Our aim is to investigate the effects of etoricoxib on testicular I/R damage induced with torsion-detorsion (TD). The etoricoxib + torsion-detorsion (ETD) groups of animals were given etoricoxib in 50 and 100 mg/kg of body weight (ETD-50 and ETD-100), while the testes torsion-detorsion (TTD) and sham operation rat group (SOG) animals were given single oral doses of distilled water as a solvent. TTD, ETD-50 and ETD-100 groups were subjected to 720° degrees torsion for four hours, and detorsion for four hours. The SOG group was not subjected to this procedure. Biochemical, gene expression and histopathological analyses were carried out on the testicular tissues. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were significantly higher, and the levels of total glutathione (tGSH) and glutathione reductase (GSHRd) were significantly lower in the TTD group, compared to the ETD-50, ETD-100 and SOG groups. Etoricoxib at a dose of 100 mg/kg better prevented I/R damage than the 50 mg/kg dose. Etoricoxib may be useful in clinical practice in the reduction of I/R damage on testes caused by torsion-detorsion.
RESUMO
AIM: To investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries. METHODS: Rats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret® + ovarian IR (KIR-50); 100 mg/kg Kineret® + ovarian IR (KIR-100); and sham operation (SOC). KIR-50 (n = 10) and KIR-100 (n = 10) groups received an intraperitoneal injection of Kineret® at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method. The results were compared between the groups. RESULTS: In rats in which IR occurred, oxidant parameters, such as malondialdehyde (MDA) and myeloperoxidase (MPO), were increased, the level of proinflammatory interleukin 1 beta (IL-1ß) was elevated and total glutathione (tGSH) as an antioxidant was decreased in the ovarian tissues. Administration of Kineret® at a dose of 100 mg/kg inhibited the increase of MDA, MOP and IL-1ß and a decrease in tGSH caused by IR more significantly than administration of Kineret® at a dose of 50 mg/kg. In addition, 100 mg/kg Kineret® significantly decreased severe hemorrhage, degeneration and inflammatory signs in the follicular cells, caused by IR. Kineret® at 100 mg/kg markedly ameliorated increased apoptosis in ovarian tissue with IR more significantly than 50 mg/kg kineret. CONCLUSION: Our findings indicate that Kineret® might be useful in clinical practice for the treatment of damage that may occur as a result of ovarian torsion.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Ovário/metabolismo , Ovário/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Caspase 3/genética , Modelos Animais de Doenças , Feminino , Expressão Gênica/efeitos dos fármacos , Glutationa/genética , Interleucina-1beta/genética , Malondialdeído/metabolismo , Ovário/efeitos dos fármacos , Peroxidase/genética , Ratos , Ratos Wistar , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologiaRESUMO
High numbers of proinflammatory cells (PMNLs), which are carried by the blood to ischemic tissue during reperfusion, are considered responsible for inducing the inflammatory response that occurs in ischemia-reperfusion (I/R) injury. Our objective was to determine the controlled reperfusion (CR) interval duration (CRID) that would minimize the injury caused by the PMNLs that infiltrate ischemic tissue. Animal groups were divided into the following groups: Sham group, ovarian I/R group (OIR), and ovarian ischemia controlled-reperfusion groups OICR-1, OICR-2, OICR-3, OICR-4, OICR-5, OICR-6, which had their ovarian artery opened and then closed for 10, 8, 6, 4, 2, or 1 s, respectively. The results show that the COX-2 activity and the gene expression decreased while the COX-1 activity and the gene expression were found to be increased in parallel to the shortening of the period in CRID. From the histopathological examinations, the findings of hemorrhage, edema, congested vascular structures, degenerated cells, and migration and adhesion of PMNLs were scaled as follows: Sham group < OICR-6 < OICR-5 < OICR-4 < OICR-3 < OICR-2 < OICR-1. The results from the histopathological assessments were consistent with the molecular and biochemical findings. In conclusion, our findings suggest that increased COX-2 activity plays a role in I/R injury of the rat ovary, and that controlled reperfusion for 3, 2, or 1 s following 2 h of ischemia may attenuate the effects of I/R injury.
Assuntos
Regulação Enzimológica da Expressão Gênica , Infiltração de Neutrófilos , Neutrófilos/imunologia , Ooforite/prevenção & controle , Ovário/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Reperfusão , Animais , Adesão Celular , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Edema/etiologia , Edema/prevenção & controle , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Ooforite/imunologia , Ooforite/metabolismo , Ooforite/patologia , Ovário/imunologia , Ovário/metabolismo , Ovário/patologia , Ratos Wistar , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de TempoRESUMO
BACKGROUND/AIMS: To investigate the importance of antioxidant activity in infertility caused by cisplatin in rats. METHODS: Rats in cisplatin control (CG), Vitamin E + cisplatin (ECG), Vitamin C + cisplatin (CCG), Hippophae rhamnoides extract (HRE) + cisplatin (HRECG), and thiamine pyrophosphate (TPP) + cisplatin (TPPCG) groups were injected intraperitoneally (ip) with (100 mg/kg) Vitamin E, Vitamin C, HRE, and TPP, respectively. One hour later, ip cisplatin was administered (5 mg/kg), and then antioxidant medications were continued for 10 days. Cisplatin + Vitamin E (CEG-1), cisplatin + Vitamin C (CCG-1), cisplatin + HRE (CHREG-1), and cisplatin + TPP (TPPCG-1) rats received cisplatin (5 mg/kg, ip) and were kept for 10 days. At the end of that period, rats received antioxidant medications for 10 days. (n = 12, for each group). Six rats from each group were sacrificed. Ovaries were removed to measure malondialdehyde, total glutathione, glutathione S-transferase, and glutathione reductase levels. The remaining rats were kept in a suitable laboratory environment. RESULTS: Cisplatin-induced oxidative stress was best prevented by HRE, Vitamin E, Vitamin C, and TPP, in that order. However, infertility caused by cisplatin was only prevented and treated by TPP. CONCLUSION: Oxidative stress is not a major component in the pathogenesis of cisplatin-associated infertility.
Assuntos
Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Cisplatino/toxicidade , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Modelos Animais de Doenças , Feminino , Infertilidade Feminina/induzido quimicamente , Ratos , Ratos WistarRESUMO
Background: The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. Aims: In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Methods: Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100 mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150 mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7 days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. Results: CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Conclusion: Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.