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BACKGROUND: Metamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach. AIMS: Our study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats. METHODS: Eighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues. RESULTS: Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups' lung and gastric tissues. CONCLUSION: Metamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.
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Anti-Inflamatórios não Esteroides , Dipirona , Coração , Rim , Fígado , Pulmão , Estômago , Animais , Dipirona/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Anti-Inflamatórios não Esteroides/toxicidade , Masculino , Ratos , Coração/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/patologia , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Glutationa/metabolismo , Catalase/metabolismo , Miocárdio/patologia , Miocárdio/metabolismoRESUMO
BACKGROUND: Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. METHODS: Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20â¯mg/kg, 2×1) was injected intramuscularly. Sertraline (30â¯mg/kg, 1×1) and tianeptine (5â¯mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. RESULTS: Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p<0.001), sertraline and tianeptine were close to HG (p>0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). CONCLUSION: Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.
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Meperidina , Reprodução , Sertralina , Tiazepinas , Animais , Feminino , Sertralina/farmacologia , Tiazepinas/farmacologia , Ratos , Meperidina/farmacologia , Masculino , Reprodução/efeitos dos fármacos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Antioxidantes/farmacologia , Prolactina/sangueRESUMO
AIM: To investigate the effect of lacidipine, thiamine pyrophosphate (TPP) and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats. METHODS: Male albino Wistar rats were categorized as those who underwent sham surgery (SG), right and left common carotid cross-clamping and unclamping procedure (CCU), lacidipine+CCU (LCCU), TPP+CCU (TCCU), and combination of lacidipine and TPP (LTC)+CCU (LTCCU). One hour before anesthesia, the LCCU (n=6) received lacidipine (4 mg/kg, orally) and the TCCU (n=6) received TPP (20 mg/kg, intraperitoneally). The SG (n=6) and CCU (n=6) received the same volume of distilled water from the same route. After anesthesia (60 mg/kg ketamine, intraperitoneally), the necks of the rats were opened in the midline. Ischemia was created for 10min by placing clips on the right and left common carotid arteries. Rats in the SG only underwent subcutaneous incision. After 10min, the clips were removed and reperfusion was achieved for six days. Then, the animals were euthanized (120 mg/kg ketamine, intraperitoneally) and the levels of oxidant, antioxidant and proinflammatory cytokines in the eye tissues were determined. The retinal tissue of the eye was also examined histopathologically. RESULTS: Lacidipine, TPP, and LTC significantly prevent the increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-1ß (IL-1ß), and IL-6 levels, decrease in total glutathione levels, superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats. The impact of these drugs on protection is determined to be LTC>lacidipine>TPP. CONCLUSION: As a result of the study, it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.
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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.
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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.
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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.
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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.
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Hippophae , Estomatite , Ratos , Animais , Fluoruracila/toxicidade , Antioxidantes/farmacologia , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Interleucina-6 , Oxidantes/farmacologia , Mucosa IntestinalRESUMO
Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.
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Indometacina , Úlcera Gástrica , Ratos , Animais , Indometacina/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Famotidina/efeitos adversos , Felodipino/efeitos adversos , Ratos Wistar , Anti-Inflamatórios não Esteroides/efeitos adversos , Antioxidantes/farmacologiaRESUMO
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.
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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
Background: Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties. Aims: To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats. Methods: Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50 mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20 mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and nuclear factor kappa b (NF-κB) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically. Results: In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-κB, IL-1ß, and TNF-α levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure. Conclusion: Carvacrol may be used for liver damage caused by acrylamide.
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Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.
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Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ratos , Animais , Acetaminofen/toxicidade , Acetaminofen/metabolismo , Trifosfato de Adenosina/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado , Antioxidantes/farmacologia , Estresse OxidativoRESUMO
BACKGROUND: Ischemia/reperfusion (I/R) can cause damage to distant organs. Rutin is known to have antioxidant and anti-inflammatory properties, and inhibits cytokine and polymorphonuclear leukocyte (PMNL) infiltration. It may prevent the development of reperfusion injury. OBJECTIVES: This study aimed to examine the role of PMNLs in distant organ (lung) injury after a liver I/R procedure, and to evaluate the protective effects of rutin in rats using biochemical and immunohistochemical methods. MATERIAL AND METHODS: In this study, 18 Wistar albino male rats (255-275 g) were used. Experimental animals were divided into 3 groups: a liver I/R (LIR) group, a 50 mg/kg rutin+liver I/R (RLIR) group and a sham operation (SG) control group. Experimental results obtained from the RLIR group were compared with the LIR and SG groups. RESULTS: Blood malondialdehyde (MDA) levels in the RLIR and SG groups were significantly lower compared to the LIR group (p < 0.001). Blood myeloperoxidase (MPO) activity in the RLIR and SG groups was significantly lower compared to the LIR group (p < 0.001). Total glutathione (tGSH) levels in the RLIR and SG groups were significantly higher compared to the LIR group (p < 0.001). CONCLUSIONS: Rutin can be used to prevent distant organ (lung) damage due to liver I/R. However, more extensive studies are needed on this issue.
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Lesão Pulmonar , Traumatismo por Reperfusão , Ratos , Animais , Ratos Wistar , Rutina/farmacologia , Neutrófilos , Isquemia , Estresse Oxidativo , Reperfusão , Traumatismo por Reperfusão/prevenção & controle , Pulmão , Fígado , MalondialdeídoRESUMO
Bevacizumab is a recombinant humanized monoclonal antibody whose adverse effects include cardiotoxicity. We investigated whether using adenosine triphosphate (ATP) or benidipine either separately or together protects against cardiac damage induced by bevacizumab in rats. Forty Wistar albino male rats were allocated to five groups of eight: bevacizumab (Bv), ATP + bevacizumab (ABv), benidipine + bevacizumab (BBv), ATP + benidipine + bevacizumab (ABBv) and untreated controls. Rats in the ABv group were injected intraperitoneally (i.p.) with 2 mg/kg ATP. The BBv group was given 4 mg/kg benidipine by oral gavage. The ABBv group was injected i.p. with 2 mg/kg ATP and simultaneously administered 4 mg/kg benidipine orally. One hour after administration of ATP, benidipine or normal saline, the Bv, ABv, BBv and ABBv groups were injected i.p. with 10 mg/kg bevacizumab. Malondialdehyde (MDA) and total glutathione (tGSH) levels were measured in cardiac tissue, and troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in blood samples. Tissue samples were examined for histopathology. We found the lowest TP I, CK-MB and MDA levels and the highest tGSH level in the ABBv group; these results were similar to the control group. Nuclei of cardiomyocytes in the BV group were misshapen and shrunken, and myofibers were disrupted; we also observed eosinophilic degeneration and interstitial edema. Blood capillaries were dilated and congested. We observed amelioration of these findings in the ABBv group. We found that ATP and benidipine alone or in combination reduced cardiac damage associated with the use of bevacizumab. ATP + benidipine combined therapy produced the most favorable results.
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Trifosfato de Adenosina , Cardiotoxicidade , Ratos , Animais , Bevacizumab/farmacologia , Ratos Wistar , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Glutationa/metabolismo , Estresse OxidativoRESUMO
Introduction: In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Material and methods: Sixty-four male albino Wistar rats weighing 285-295 g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. Results: There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. Conclusion: The combination of the L-type Ca2+ channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.
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Cobalt is a trace element that increases lipid peroxidation and malondialdehyde levels and reduces the antioxidant defense mechanisms of nerve cells. High levels of cobalt exposure may cause peripheral neuropathy, but the mechanism behind this has not yet been elucidated. Taxifolin is a flavonoid whose antioxidant and antiinflammatory properties are wellknown. We aimed to investigate the effect of taxifolin on cobaltinduced oxidative sciatic nerve damage. Eighteen albino male Wistar rats were assigned to three groups: Control, Cobalt, and Taxifolin + Cobalt groups. Total oxidant and total antioxidant status and levels of malondialdehyde, total glutathione, and superoxide dismutase were measured to determine the effect of taxifolin on cobaltinduced sciatic nerve injury. The following statistically significant effect of taxifolin was observed: It prevented cobaltinduced oxidative sciatic nerve damage by reducing malondialdehyde levels and total oxidant status and increasing total antioxidant status, total glutathione levels, and superoxide dismutase levels. In a histopathological analysis, we observed similar findings in Control and Taxifolin + Cobalt groups. We determined that taxifolin is effective in preventing cobaltinduced oxidative damage in sciatic nerve injury.
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Antioxidantes , Oligoelementos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Cobalto/toxicidade , Glutationa/metabolismo , Malondialdeído , Oxidantes/farmacologia , Estresse Oxidativo/fisiologia , Quercetina/análogos & derivados , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Superóxido Dismutase/metabolismo , Oligoelementos/farmacologiaRESUMO
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.
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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
The role of oxidative stress and inflammation in the pathogenesis of cyclophosphamide-related side effects has been demonstrated in previous studies. This study aimed to investigate the effect of taxifolin, due to its antioxidant and anti-inflammatory properties, on cyclophosphamide-induced oxidative and inflammatory bladder injury in albino Wistar rats. The taxifolin+cyclophosphamide (TCYC) group was given 50 mg/kg of taxifolin orally by gavage. Normal saline was used as a solvent for the cyclophosphamide (CYC) group and the healthy control (HC) group. One hour after taxifolin administration, 75 mg/kg of cyclophosphamide was intraperitoneally injected in the TCYC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, biochemical markers were studied in the excised bladder tissues and histopathological evaluations were conducted. In the histopathological evaluation of the CYC group, severe epithelial irregularity, dilatation, congestion, and polymorphonuclear leukocyte accumulation in the vascular structures were observed. Additionally, the malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels, the total oxidant status (TOS), and the oxidative stress index (OSI) values were significantly higher, and the total glutathione (tGSH) levels and total antioxidant status (TAS) were significantly lower in the CYC group in comparison to the HC group (P<0.001). Taxifolin reduced the cyclophosphamide-induced increases in the MDA, TNF-α, IL-1ß, and IL-6 levels and the TOS and OSI values; it decreased the tGSH and TAS levels and reduced histopathological damage (P<0.001). Taxifolin may be useful in the treatment of cyclophosphamide-induced bladder damage.
Assuntos
Antioxidantes , Fator de Necrose Tumoral alfa , Ratos , Animais , Antioxidantes/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Bexiga Urinária/metabolismo , Interleucina-6 , Malondialdeído , Estresse Oxidativo , Glutationa/metabolismo , Ciclofosfamida/efeitos adversos , Ratos WistarRESUMO
Hepatotoxicity is a common side effect of doxorubicin (Dox) treatment of cancer. Liv-52 is an ayurvedic medicine that is reported to ameliorate liver injury due to oxidative stress. We investigated the effects of Liv-52 on Dox induced oxidative damage to liver tissues of rats using biochemical and histopathological techniques. Thirty male rats were assigned randomly into three equal groups: control (CG), Dox group (DG) Liv-52 + Dox group (LD). Rats in the LD group received 50 mg/kg Liv-52 in distilled water via gastric gavage. Distilled water was given via the same route to the rats in the DG and CG groups. Rats in the LD and DG groups were injected intraperitoneally with 5 mg/kg Dox 1 h after administration of Liv-52 or distilled water. The procedure was repeated daily for 7 days. On day 8, the animals were sacrificed, and serum and tissue biochemical and histopathological assays were performed. The malondialdehyde level was increased significantly in the DG group, while glutathione and superoxide dismutase levels were significantly lower in the DG group compared to the LD and CG groups. The highest levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were found in the DG group, while the lowest levels were found in the CG group, which exhibited levels similar to those of the LD group. Treatment with Liv-52 prior to Dox treatment reduced the histopathologic changes in the Dox group. Therefore, pre-treatment with Liv-52 protected against Dox induced oxidative stress and hepatotoxicity.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doxorrubicina , Estresse Oxidativo , Extratos Vegetais , Animais , Masculino , Ratos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doxorrubicina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
Propofol may cause an increase in reactive oxygen species in the body. In this study, we tested the effect of antioxidant thiamine pyrophosphate (TPP) on propofol-induced liver damage. The eighteen rats were split into three groups: HG, healthy; PP, propofol-treated (50 mg/kg) and PT, treated with propofol (50 mg/kg) and TPP (25 mg/kg). Total glutathione (tGSH), total oxidant (TOS), and total antioxidant (TAS) levels were tested together with aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and malondialdehyde (MDA). Histopathological examination of the tissues was performed. We have found that levels of MDA, TOS, ALT, AST, and LDH were all higher in PP group than in HG and PT groups (p < 0.05). In PP group, the TAS and tGSH levels were statistically substantially lower. The PT for oxidants levels showed a statistically significant reduction. In PT group, the levels of antioxidants were found to be considerably higher. The epitheliums, glands, and vascular structures of the PTs were histologically close to normal. By boosting antioxidants, TPP may help to reduce propofolinduced liver damage.