RESUMO
Exposure to higher levels of arsenic is a serious threat affecting human health worldwide. We investigated the protective role of betaine (N,N,N-trimethylglycine) against sodium arsenite-induced renal dysfunction in rats. Sodium arsenite (5 mg/kg, oral) was given to rats for 4 weeks to induce nephrotoxicity. Betaine (125 and 250 mg/kg, oral) was administered in rats for 4 weeks along with sodium-arsenite feeding. Arsenic-induced renal dysfunction was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium, and microproteinuria. Oxidative stress in rat kidneys was determined by assaying thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels. Furthermore, hydroxyproline assay was done to assess renal fibrosis in arsenic intoxicated rats. Hematoxylin-eosin and picrosirius red staining revealed pathological alterations in rat kidneys. Renal endothelial nitric oxide synthase (eNOS) expression was determined by immuno-histochemistry. Concurrent administration of betaine abrogated arsenic-induced renal biochemical and histological changes in rats. Betaine treatment significantly attenuated arsenic-induced decrease in renal eNOS expression. In conclusion, betaine is protective against sodium arsenite-induced renal dysfunction, which may be attributed to its anti-oxidant activity and modulation of renal eNOS expression in rat kidneys.
Assuntos
Arsênio , Arsenitos , Nefropatias , Animais , Ratos , Antioxidantes/metabolismo , Arsenitos/toxicidade , Betaína/farmacologia , Creatinina , Glutationa/metabolismo , Hidroxiprolina/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Potássio , Ratos Wistar , Sódio , Superóxidos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ureia , Ácido ÚricoRESUMO
Arsenic exposure causes immense health distress by increasing risk of cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. The present study explored the role of inducible nitric oxide synthase (iNOS) inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats. Female Sprague Dawley rats were subjected to arsenic toxicity by administering sodium arsenite (5 mg/kg/day, oral) for 4 weeks. The iNOS inhibitors, S-methylisothiourea (10 mg/kg, i.p.) and aminoguanidine (100 mg/kg, i.p.) were given one hour before sodium arsenite administration in rats for 4 weeks. Sodium arsenite led rise in serum creatinine, urea, uric acid, electrolytes (potassium, fractional excretion of sodium), microproteinuria, and decreased creatinine clearance (p < 0.001) indicated renal dysfunction in rats. Arsenic-intoxication resulted in significant oxidative stress in rat kidneys, which was measured in terms of increase in lipid peroxides, superoxide anion generation and decrease in reduced glutathione (p < 0.001) levels. A threefold increase in renal hydroxyproline level in arsenic intoxicated rats indicated fibrosis. Hematoxylin-eosin staining indicated tubular damage, whereas picrosirius red staining highlighted collagen deposition in rat kidneys. S-methylisothiourea and aminoguanidine improved renal function and attenuated arsenic led renal oxidative stress, fibrosis, and decreased the kidney injury score. Additionally, arsenite-intoxication resulted in significant rise in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, and bilirubin (p < 0.001) along with multi-fold increase in oxidative stress, fibrosis and liver injury score in rats, which was significantly (p < 0.001) attenuated by concurrent administration of iNOS inhibitors). Hence, it is concluded that iNOS inhibitors attenuate sodium arsenite-induced renal and hepatic dysfunction in rats.
Assuntos
Arsênio , Arsenitos , Animais , Arsênio/metabolismo , Arsenitos/metabolismo , Arsenitos/toxicidade , Feminino , Fibrose , Rim/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Compostos de SódioRESUMO
Fibromyalgia is a common, chronic, and generalized pain syndrome that is often associated with comorbid depression. The etiology of fibromyalgia is complex; most researchers have documented that the hallmark symptoms are due to the central nervous system's abnormal functioning. Neurotransmitters such as serotonin, norepinephrine, and glutamate, have been reported to be key regulators of fibromyalgia syndrome. Daphnetin is a 7, 8 dihydroxy coumarin widely distributed in Thymelaeaceae family plants, possessing various activities such as anti-arthritic, anti-tumor, anti-malarial, and anti-parasitic. The present study was designed to explore the potential of daphnetin against reserpine-induced fibromyalgia in mice. In mice, a fibromyalgia-like state was achieved by injecting reserpine (0.5 mg/kg, s.c) continuously for 3 days. All behavioral tests were conducted on the 4th and 6th day of experimentation. Reserpine administration significantly increased the mechanical hypersensitivity in electronic von Frey (eVF) and pressure application measurement (PAM) tests. It also increased the immobility period and time to reach the platform in force swim test (FST) and Morris water maze (MWM) test, respectively. In the biochemical analysis, reserpine treatment upregulated the monoamine oxidase-A (MAO-A) activity and level of glutamate, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and thiobarbituric acid reactive substances (TBARS). Whereas, it decreased the level of glutathione (GSH), dopamine, serotonin, and norepinephrine. Daphnetin pretreatment attenuated the behavioral and biochemical changes induced by reserpine. Thus, the current investigation results delineate that daphnetin might exert its protective effect by inhibiting inflammatory stress and MAO-A-mediated neurotransmitter depletion and oxidative stress.
Assuntos
Fibromialgia , Reserpina , Animais , Modelos Animais de Doenças , Fibromialgia/induzido quimicamente , Fibromialgia/tratamento farmacológico , Camundongos , Monoaminoxidase , Reserpina/toxicidade , Umbeliferonas/farmacologiaRESUMO
Ischemia/reperfusion (I/R) is one of the common reasons for acute kidney injury (AKI) and we need to develop effective therapies for treating AKI. We investigated the role of fenofibrate against I/R-induced AKI and associated hepatic dysfunction in rats. In male wistar albino rats, renal pedicle occlusion for 40 min and 24 h reperfusion resulted in AKI. I/R-induced AKI was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium and urinary microproteins. Oxidative stress in rat kidneys was quantified by assaying superoxide anion generation, thiobarbituric acid reactive substances, and reduced glutathione levels. AKI-induced hepatic damage was quantified by assaying serum aminotransferases, alkaline phosphatase and bilirubin levels. Moreover, serum cholesterol, high density lipoprotein and triglycerides were quantified. Hematoxylin-eosin staining of renal and hepatic tissues was done and the kidney and liver injury scores were determined. Immunohistology of endothelial nitric oxide synthase (eNOS) was done in rat kidneys. Fenofibrate was administered for 1 week before subjecting rats to AKI. In separate group, the nitric oxide synthase inhibitor, L-nitroarginine methyl ester (L-NAME) was administered prior to fenofibrate treatment. In I/R group, significant alteration in the serum/urine parameters indicated AKI and hepatic dysfunction along with marked increase in kidney and liver injury scores. Treatment with fenofibrate attenuated AKI and associated hepatic dysfunction. Moreover, I/R-induced decrease in renal eNOS expression was abrogated by fenofibrate. Pre-treatment with L-NAME abolished fenofibrate mediated reno- and hepato-protective effects. In conclusion, fenofibrate attenuates I/R-induced AKI and associated hepatic dysfunction putatively through modulation of eNOS expression.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Fenofibrato/farmacologia , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Traumatismo por Reperfusão/complicações , Animais , Biomarcadores/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
Fibromyalgia is a refractory syndrome characterized by chronic wayward pain and complex co-morbid psychological trepidation. The current treatments have a limited role and proper clinical benefits are far from satisfactory. Naturally occurring coumarins such as osthole are known to have analgesic and anti-inflammatory activities. Therefore, the current investigation was designed to explore the potential of natural coumarin esculetin (2.5, 5, and 10 mg/kg) in mitigating reserpine-induced fibromyalgia in Swiss albino mice. Esculetin is a 6,7 dihydroxy-coumarin obtained from various plant sources such as Aesculus hippocastanum L, Ceratostigma willmottianum, Citrus limonia, etc. Reserpine (0.5 mg/kg/day s.c.) treatment for first 3 days, significantly altered the behavior of mice as evidenced by reduced paw withdrawal threshold in pressure application measurement (PAM) test and electronic von-Frey (eVF) test, increased immobility time in forced swim test (FST), increased latency to reach the platform in Morris water maze (MWM) test and reduced number of square crossed in the open field test (OFT). These behavioral deficits with reserpine treatment were integrated with a reduced level of serotonin (5-HT), reduced glutathione (GSH), along with an increase in monoamine oxidase-A (MAO-A) activity, pro-inflammatory cytokines (IL-1ß, TNF-α), thiobarbituric acid reactive substances (TBARS) and glutamate level. Esculetin (10 mg/kg/day i.p) treatment for 5 days, significantly abrogated reserpine induced behavioral and biochemical alterations. Whereas, no significant improvement was observed with lower doses of esculetin i.e. 2.5 and 5 mg/kg.
Assuntos
Analgésicos/uso terapêutico , Fibromialgia/tratamento farmacológico , Interleucina-1beta/metabolismo , Monoaminoxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Umbeliferonas/uso terapêutico , Animais , Feminino , Fibromialgia/induzido quimicamente , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Neurotransmissores/metabolismo , Teste de Campo Aberto/efeitos dos fármacos , Reserpina , Serotonina/metabolismoRESUMO
Continuous-wave (cw) squeezed states of light have applications in sensing, metrology and secure communication. In recent decades their efficient generation has been based on parametric down-conversion, which requires pumping by externally generated pump light of twice the optical frequency. Currently, there is immense effort in miniaturizing squeezed-light sources for chip-integration. Designs that require just a single input wavelength are favored since they offer an easier realization. Here we report the first observation of cw squeezed states generated by self-phase modulation caused by subsequent up and down conversions. The wavelengths of input light and of balanced homodyne detection are identical, and 1550 nm in our case. At sideband frequencies around 1.075 GHz, a nonclassical noise reduction of (2.4 ± 0.1) dB is observed. The setup uses a second-order nonlinear crystal, but no externally generated light of twice the frequency. Our experiment is not miniaturized, but might open a route towards simplified chip-integrated realizations.
RESUMO
We investigated the involvement of peroxisome proliferator activated receptor-γ (PPAR-γ)/endothelial nitric oxide synthase (eNOS) pathway in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats. To induce AKI, rats underwent 40 min of bilateral renal ischemia followed by 24 h of reperfusion. I/R-induced kidney damage was quantified by measuring serum creatinine, creatinine clearance, urea nitrogen, uric acid, potassium, fractional excretion of sodium, microproteinuria, and renal oxidative stress (thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione). Hematoxylin eosin stain demonstrated renal histology, while renal expression of apoptotic markers (Bcl-2, Bax), PPAR-γ and eNOS were quantified by immunohistochemistry. Estradiol (1 mg/kg, i.p.) was administered 30 min before I/R in rats. In separate groups, PPAR-γ antagonist, BADGE (30 mg/kg, i.p.), and NOS inhibitor, L-NAME (20 mg/kg, i.p.) were administered prior to estradiol treatment, which was followed by I/R in rats. I/R caused significant renal damage as demonstrated by biochemical (serum/urine), renal oxidative stress and histological changes alongwith increased expression of Bax and decreased levels of Bcl-2, PPAR-γ and eNOS, which were prevented by estradiol. Pre-treatment with BADGE and L-NAME abolished estradiol mediated renoprotection. Notably, I/R + estradiol + BADGE group revealed decreased expression of PPAR-γ and eNOS in renal tissues. In I/R + estradiol + L-NAME group, eNOS expression was reduced while PPAR-γ levels remained unchanged. These results suggest that estradiol modulates PPAR-γ which consequently regulates eNOS expression in rat kidneys. We conclude that estradiol protects against I/R-induced AKI through PPAR-γ stimulated eNOS activation in rats.
Assuntos
Injúria Renal Aguda , Estradiol/farmacocinética , Óxido Nítrico Sintase Tipo III/metabolismo , PPAR gama/metabolismo , Traumatismo por Reperfusão , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Ativação Enzimática/efeitos dos fármacos , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteína X Associada a bcl-2/metabolismoRESUMO
In the present study, we investigated possible involvement of N-methyl-D-aspartate receptors (NMDAR) in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute renal failure (ARF) in rats. Bilateral renal ischemia of 40 min followed by reperfusion for 24 h induced ARF in male wistar rats. Quantification of serum creatinine, creatinine clearance (CrCl), blood urea nitrogen (BUN), uric acid, potassium, fractional excretion of sodium (FeNa), and urinary microproteins was done to assess I/R-induced renal damage in rats. Oxidative stress in kidneys was measured in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels. Hematoxylin & eosin and periodic acid Schiff stains were used to reveal structural changes in renal tissues. Estradiol benzoate (0.5 and 1.0 mg/kg, intraperitoneally, i.p.) was administered 1 h prior to I/R in rats. In separate groups, rats were treated with NMDAR agonists, glutamic acid (200 mg/kg, i.p.), and spermidine (20 mg/kg, i.p.) before administration of estradiol. Marked increase in serum creatinine, BUN, uric acid, serum potassium, FeNa, microproteinuria, and reduction in CrCl demonstrated I/R-induced ARF in rats. Treatment with estradiol mitigated I/R-induced changes in serum/urine parameters. Moreover, estrogen attenuated oxidative stress and structural changes in renal tissues. Prior administration of glutamic acid and spermidine abolished estradiol mediated renoprotection in rats. These results indicate the involvement of NMDAR in estradiol mediated renoprotective effect. In conclusion, we suggest that NMDAR antagonism serves as one of the mechanisms in estradiol-mediated protection against I/R-induced ARF in rats.
Assuntos
Injúria Renal Aguda/prevenção & controle , Estradiol/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Rim/irrigação sanguínea , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/prevenção & controle , Ratos , Ratos Wistar , Ácido Úrico/sangueRESUMO
BACKGROUND: Lawsonia inermis (Lythraceae) is an ethnomedicinal plant, traditionally known for curing several ailments such as skin diseases, bacterial infections, jaundice, renal lithiases and inflammation etc. The present work deals with assessment of in vitro antioxidant and in vivo hepatoprotective potential of butanolic fraction (But-LI) of Lawsonia inermis L. leaves. METHODS: Antioxidant activity was evaluated using deoxyribose degradation, lipid peroxidation inhibition and ferric reducing antioxidant power (FRAP) assay. In vivo protective potential of But-LI was assessed at 3 doses [100, 200 & 400 mg/kg body weight (bw)] against 2-acetylaminofluorene (2-AAF) induced hepatic damage in male Wistar rats. RESULTS: But-LI effectively scavenged hydroxyl radicals in deoxyribose degradation assay (IC50 149.12 µg/ml). Fraction also inhibited lipid peroxidation and demonstrated appreciable reducing potential in FRAP assay. Treatment of animals with 2-AAF resulted in increased hepatic parameters such as SGOT (2.22 fold), SGPT (1.72 fold), ALP (5.68 fold) and lipid peroxidation (2.94 fold). Different concentration of But-LI demonstrated pronounced protective effects via decreasing levels of SGOT, SGPT, ALP and lipid peroxidation altered by 2-AAF treatment. But-LI administration also restored the normal liver architecture as evident from histopathological studies. CONCLUSIONS: The present experimental findings revealed that phytoconstituents of Lawsonia inermis L. possess potential to effectively protect rats from the 2-AAF induced hepatic damage in vivo possibly by inhibition of reactive oxygen species and lipid peroxidation.
Assuntos
Lawsonia (Planta)/química , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , 2-Acetilaminofluoreno , Animais , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Peroxidação de Lipídeos , Fígado/patologia , Masculino , Ratos WistarRESUMO
The present study investigated the role of N-methyl-D-aspartate (NMDA) receptors in pioglitazone-mediated protection against renal ischemia reperfusion injury (IRI) in rats. Male wistar rats were subjected to 40 min of bilateral renal ischemia followed by reperfusion for 24 h to induce kidney injury. The renal damage was evaluated by measuring serum creatinine, creatinine clearance, blood urea nitrogen, uric acid, electrolytes, and microproteinuria in rats. Oxidative stress in renal tissues was quantified in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. Hematoxylin-eosin and periodic acid Schiff staining of renal tissues were performed to observe histological changes. Pioglitazone (20 and 40 mg/kg) was administered 1 h prior to ischemia in rats. In separate groups, NMDA agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered 1 h prior to pioglitazone treatment, followed by renal IRI in rats. Ischemia reperfusion resulted in marked renal damage with significant changes in serum and urine parameters along with marked oxidative stress and histological changes in kidneys. Pioglitazone treatment afforded anti-oxidant effect and renoprotection in a dose-dependent manner in rats. Pioglitazone-mediated renoprotection was attenuated by glutamic acid and spermidine pretreatment in rats, which indicated the role of NMDA receptors in pioglitazone-mediated protection. It is concluded that NMDA antagonism serves as one of the mechanisms in pioglitazone-mediated protection against renal IRI in rats.
Assuntos
Nefropatias , Receptores de N-Metil-D-Aspartato , Traumatismo por Reperfusão , Tiazolidinedionas/farmacologia , Animais , Nefropatias/metabolismo , Nefropatias/prevenção & controle , Masculino , Pioglitazona , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controleRESUMO
BACKGROUND: Estrogen is reported to be renoprotective agent in various preclinical studies, attributing to its antioxidant and anti-inflammatory potential. The aim of present study was to investigate the involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ) in estrogen-mediated protection against renal ischemia reperfusion injury (IRI) in rats. MATERIALS AND METHODS: The renal damage induced by IRI (40-min ischemia and 24-h reperfusion) was assessed by measuring serum creatinine, creatinine clearance, blood urea nitrogen, serum uric acid, electrolytes, and microproteinuria in rats. The myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin-eosin and periodic acid schiff staining of renal tissues were done to demonstrate histopathologic changes. Estrogen (0.2, 0.5, and 1.0 mg/kg, i.p.) was administered 1 h before subjecting rats to renal IRI. Separately, bisphenol A diglycyl ether (BADGE, 30 mg/kg, i.p.), a PPAR-γ receptor antagonist, was given before estrogen administration followed by IRI in rats. RESULTS: The ischemia reperfusion demonstrated renal damage in rats with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. Estrogen administration demonstrated marked renoprotection that was attenuated by BADGE pretreatment in rats. CONCLUSIONS: It is concluded that PPAR-γ agonism serves as one of the mechanisms in estrogen-mediated renoprotection.
Assuntos
Injúria Renal Aguda/prevenção & controle , Estrogênios/uso terapêutico , PPAR gama/agonistas , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Biomarcadores/metabolismo , Esquema de Medicação , Estrogênios/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , PPAR gama/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator-activated receptor γ (PPAR-γ) in sildenafil-mediated protection against ischemia-reperfusion-induced acute kidney injury (AKI) in rats. MATERIALS AND METHODS: The rats were subjected to ischemia-reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-γ receptor antagonist, was given before sildenafil administration followed by IRI. RESULTS: The ischemia-reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia-reperfusion-induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-γ agonism in the sildenafil-mediated renoprotective effect. CONCLUSIONS: It is concluded that sildenafil protects against ischemia-reperfusion-induced AKI through PPAR-γ agonism in rats.
Assuntos
Injúria Renal Aguda/prevenção & controle , PPAR gama/agonistas , Inibidores da Fosfodiesterase 5/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Citrato de Sildenafila/uso terapêutico , Injúria Renal Aguda/patologia , Animais , Compostos Benzidrílicos , Avaliação Pré-Clínica de Medicamentos , Compostos de Epóxi , Rim/patologia , Testes de Função Renal , Masculino , Estresse Oxidativo , Inibidores da Fosfodiesterase 5/farmacologia , Proteinúria/prevenção & controle , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/patologia , Citrato de Sildenafila/farmacologiaRESUMO
Reflection gratings enable light coupling to optical cavities without transmission through substrates. Gratings that have three ports and are mounted in a second-order Littrow configuration even allow the coupling to high-finesse cavities using low diffraction efficiencies. In contrast to conventional transmissive cavity couplers, however, the phase of the diffracted light depends on the lateral position of the grating, which introduces an additional noise coupling. Here, we experimentally demonstrate that this kind of noise cancels out once both diffracted output ports of the grating are combined. We achieve the same signal-to-shot-noise ratio as for a conventional coupler. From this perspective, three-port grating couplers in a second-order Littrow configuration remain a valuable approach to reducing optical absorption of cavity coupler substrates in future gravitational-wave detectors.
RESUMO
The present study investigated the possible involvement of nitric oxide/soluble guanylyl cyclase (NO/sGC) pathway in ascorbic acid (AA)-mediated protection against acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed in terms of measuring creatinine clearance (CrCl), blood urea nitrogen (BUN), plasma uric acid, potassium level, fractional excretion of sodium (FeNa), and microproteinuria. The NO level and oxidative stress in renal tissues were assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. AA (50 and 100 mg/kg, p.o.) was administered for 3 days before subjecting rats to AKI. In separate groups, the nitric oxide synthase inhibitor, L-NAME (20 mg/kg, i.p.) and sGC inhibitor, methylene blue (50 mg/kg, i.p.) was administered prior to AA treatment in rats. The significant decrease in CrCl and increase in BUN, plasma uric acid, potassium, FeNa, microproteinuria, and oxidative stress in renal tissues demonstrated ischemia-reperfusion-induced AKI in rats. The AA treatment ameliorated ischemia-reperfusion-induced AKI along with the increase in renal NO level. The pretreatment with L-NAME and methylene blue abolished protective effect of AA. It is concluded that AA protects against ischemia-reperfusion-induced AKI. Moreover, the NO/sGC pathway finds its definite involvement in AA-mediated reno-protective effect.
Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Guanilato Ciclase/fisiologia , Óxido Nítrico/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Injúria Renal Aguda/metabolismo , Animais , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Avaliação Pré-Clínica de Medicamentos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Estresse Oxidativo , Proteinúria/prevenção & controle , Ratos Wistar , Transdução de Sinais , Guanilil Ciclase Solúvel , Ácido Úrico/sangueRESUMO
Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.
Assuntos
Cardiomegalia/tratamento farmacológico , Cardiomegalia/fisiopatologia , Genfibrozila/farmacologia , Hipolipemiantes/farmacologia , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/fisiopatologia , Constrição , Modelos Animais de Doenças , Coração/fisiopatologia , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda , Masculino , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
The present study was designed to investigate the role of glycine in ischemia reperfusion-induced acute kidney injury (AKI) in rats. The AKI was induced in rats by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium, fractional excretion of sodium, and microproteinuria. The oxidative stress in renal tissues was assessed by quantification of myeloperoxidase activity, thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. Glycine (100, 200, and 400 mg/kg, i.p.) was administered to rats 30 min before subjecting to AKI. The glycinergic receptor blocker, strychnine (0.75 mg/kg i.p.), and glycine-binding site blocker at N-methyl-D-aspartate (NMDA) receptor, kynurenic acid (300 and 600 mg/kg i.p.), were used in the present study. The ischemia reperfusion induced AKI as witnessed by significant change in plasma, urinary, and tissue parameters employed in the present study. Glycine treatment increased ischemia reperfusion-induced AKI. The treatment with strychnine did not show any protection, whereas kynurenic acid ameliorated renal ischemia reperfusion-induced AKI. The results obtained in present study suggest that glycine increases ischemia reperfusion-induced renal damage through NMDA receptor agonism rather than strychnine-sensitive glycinergic receptors. Hence, it is concluded that glycine aggravates ischemia reperfusion-induced AKI. In addition, the activation of strychnine-insensitive glycine-binding site of NMDA receptors is responsible for its renal-damaging effect rather than strychnine-sensitive glycinergic receptors.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Glicina/administração & dosagem , Receptores de N-Metil-D-Aspartato/metabolismo , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Sítios de Ligação , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Ácido Cinurênico/administração & dosagem , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Estricnina/administração & dosagemRESUMO
BACKGROUND: Melatonin is released by pineal gland and maintains circadian rhythm in the body. It has been reported as renoprotective agent because of its antioxidant property. Recently, a cross talk between progesterone and melatonin has been observed in various preclinical studies. The present study investigated the involvement of progesterone receptors in melatonin-mediated protection against ischemia reperfusion induced acute kidney injury (AKI) in rats. MATERIALS AND METHODS: The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, potassium level, fractional excretion of sodium, lactate dehydrogenase activity, and microproteinuria. The oxidative stress in renal tissues was assessed by quantification of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, reduced glutathione level, and catalase activity. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. The melatonin (4 and 10 mg/kg, intraperitoneally) and progesterone receptor antagonist mifepristone (5 mg/kg, intraperitoneally) were used in the present study. RESULTS: The renal ischemia reperfusion induced AKI as indicated by significant change in serum, urinary, and tissue parameters that was ameliorated by prior treatment with melatonin. No significant difference in serum progesterone level was observed between various groups used in the present study. The prior administration of mifepristone abolished melatonin-mediated protection against AKI. CONCLUSIONS: It is concluded that melatonin treatment affords protection against ischemia reperfusion induced AKI. Moreover, progesterone receptors are essentially involved in mediating protective role of melatonin against AKI in rats.
Assuntos
Injúria Renal Aguda/prevenção & controle , Melatonina/farmacologia , Progesterona/fisiologia , Animais , Citoproteção , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Mifepristona/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Progesterona/sangue , Ratos , Ratos WistarRESUMO
BACKGROUND: Gallic acid is a polyphenolic compound and is reported to be renoprotective because of its antioxidant activity in various preclinical studies. Gallic acid has been reported to activate peroxisome proliferator-activated receptor gamma (PPAR-γ) in vitro. However, the relevance of the interplay between gallic acid and PPAR-γ in various pathologic conditions is yet to be established in vivo. The present study investigated the protective role of gallic acid against ischemia-reperfusion-induced acute kidney injury (AKI) and the possible involvement of PPAR-γ in gallic acid-mediated renoprotection. MATERIALS AND METHODS: The AKI was induced in rats through bilateral clamping of renal arteries for 40 min followed by reperfusion for 24 h. The AKI was assessed by the quantification of creatinine clearance, blood urea nitrogen, uric acid, potassium level, fractional excretion of sodium, and urinary microproteins. The oxidative stress in renal tissues was quantified in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. The histopathologic changes in renal tissues were assessed by hemotoxylin and eosin staining. The rats were administered gallic acid (50, 100, and 200 mg/kg) orally for 7 d before subjecting them to AKI. RESULTS: The renal ischemia-reperfusion induced significant changes in plasma, urinary, and tissue parameters. The administration of gallic acid at three dose levels offered a significant protection against renal ischemia-reperfusion-induced AKI. The prior treatment with PPAR-γ antagonist, bisphenol A diglycidyl ether, significantly abolished the renoprotective effect of gallic acid that confirms the involvement of PPAR-γ in gallic acid-mediated renoprotection. CONCLUSIONS: It is concluded that the activation of PPAR-γ significantly contributes toward gallic acid-mediated protection against ischemia-reperfusion-induced AKI.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Compostos Benzidrílicos/farmacologia , Nitrogênio da Ureia Sanguínea , Carcinógenos/farmacologia , Compostos de Epóxi/farmacologia , Masculino , Estresse Oxidativo/fisiologia , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Potássio/sangue , Proteinúria/tratamento farmacológico , Proteinúria/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Sódio/sangue , Ácido Úrico/sangueRESUMO
BACKGROUND: Ascorbic acid (AA) is an established antioxidant and has been used for treatment of various disorders. Recent reports suggest that administration of AA increases the level of steroids such as progesterone in the body. The present study investigated the protective role of progesterone against ischemia-reperfusion-induced acute kidney injury (AKI) and possible involvement of progesterone receptors in AA-mediated renoprotection in rats. MATERIALS AND METHODS: The male rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The rats were treated with progesterone (5 and 10 mg/kg, intraperitoneally) and AA (500 mg/kg, intraperitoneally for 1, 2, and 5 d) before AKI. In separate groups, mifepristone, the progesterone receptor antagonist was administered to rats before progesterone (10 mg/kg) and AA treatment (5 d). Various parameters including creatinine clearance, serum urea, uric acid, potassium level, fractional excretion of sodium, lactate dehydrogenase, and microproteinuria were used to assess kidney injury. Moreover, renal tissues were subjected to quantification of oxidative stress and evaluation of histopathologic changes. RESULTS: The exogenous administration of progesterone afforded protection against AKI in a dose-dependent manner that was abolished by mifepristone. The administration of AA for 1, 2, and 5 d induced significant increase in serum progesterone levels and afforded protection against AKI. The antioxidant and renoprotective effect of AA was abolished by prior treatment with mifepristone. CONCLUSIONS: It is concluded that exogenous administration of progesterone exerts significant antioxidant and renoprotective effect. Moreover, the progesterone receptors find their explicit involvement in AA-mediated renoprotection against ischemia-reperfusion-induced AKI in rats.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Progesterona/farmacologia , Receptores de Progesterona/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ferro/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Potássio/sangue , Progesterona/sangue , Ratos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Ureia/sangue , Ácido Úrico/sangueRESUMO
BACKGROUND: Sleep deprivation (SD) due to an unhealthy lifestyle poses an oxidative challenge and is closely associated with an increased risk and prevalence of different metabolic disorders. Although the negative consequences of SD are well reported on mental health little is known about its detrimental effects on liver function and lipid metabolism. Tinospora cordifolia is reported for its hepatoprotective activity in different pre-clinical model systems. The current study was designed to elucidate the cumulative effects of aging and acute SD on liver functions, oxidative stress, and lipid metabolism, and their management by butanol extract of T. cordifolia (B-TCE) using middle-aged female acyclic rats as the model system. RESULTS: Rats were divided into 4 groups: (1) Vehicle-undisturbed (VUD) (2) Vehicle-sleep deprived (VSD) (3) B-TCE pre-treated sleep-deprived (TSD) (4) B-TCE pre-treated undisturbed sleep (TUD). TSD and TUD groups were given 35 mg/kg of B-TCE once daily for 15 days followed by 12 h of sleep deprivation (6 a.m.-6 p.m.) of VSD and TSD group animals using the gentle-handling method while VUD and TUD group animals were left undisturbed. SD of VSD group animals increased oxidative stress, liver function disruption, and dyslipidemia which were ameliorated by B-TCE pre-treatment. Further, B-TCE was observed to target AMPK and its downstream lipid metabolism pathways as well as the p-Akt/cyclinD1/p-bad pathway of cell survival as possible underlying mechanisms of its hepatoprotective activity. CONCLUSIONS: These findings suggest that B-TCE being a multi-component extract may be a potential agent in curtailing sleep-related problems and preventing SD-associated hepatotoxicity and dyslipidemia in postmenopausal women.