Tag Archives: oxidative stress

Oxidative stress in COVID-19 infection

Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 63-75, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1535_11.1.63

Original Article

Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients

[Estrés oxidativo en diferentes condiciones clínicas de pacientes cubanos hospitalizados con SARS-CoV-2]

Lizette Gil-del Valle1*, Rosario Gravier-Hernández1, Mario M. Delgado-Guerra2, Joniel A. Sánchez-Márquez2, Olga E. López-Fernández2, Miguel A. Acosta-Suárez1, Teresa Rosell-Guerra1, Rodolfo Suárez-Iznaga3, Raiza Martínez-Casanueva3, Zullyt Zamora-Rodriguez4, Lidia A. Fernández-García4, Yusimit Bermudez-Alfonso1, María C. Hernández-Gonzalez-Abreu1, Gabino Garrido5**

1Institute “Pedro Kourí” (IPK), Havana, Cuba.

2Hospital Ernesto Guevara, University of Informatics’ Science, Havana, Cuba.

3Hospital Salvador Allende, Havana, Cuba.

4National Center of Scientific Research, BioCubaFarma, Havana, Cuba.

5Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad Católica del Norte, Antofagasta, Chile.

*E-mail: *lgil@ipk.sld.cu, **gabino.garrido@ucn.cl

Abstract

Context: COVID-19 related to SARS-CoV-2 infection generates inflammation with increased reactive oxygen species production. Drug treatment and others factors could influence systemic oxidative stress during pathogenic insult.

Aims: To determine the redox status in COVID-19 patients with different clinical conditions and explore the relationship between redox and hematological hemochemical variables.

Methods: In this comparative longitudinal study, blood samples were drawn from 160 individuals divided into four groups: COVID-19 asymptomatic, COVID-19 symptomatic (low and moderate symptoms), COVID-19 convalescent, and presumable healthy subjects. Demographic, redox, hematological, and hemochemical indices were assessed. Statistical analyses compared the median values of each variable and explored individual, simultaneous indices, and multivariate alteration.

Results: Relative to the healthy group, acute COVID-19, and convalescent groups had significant differences in global damage indices and antioxidant status (p<0.05). The convalescent group showed significantly higher damage (malondialdehyde, advanced oxidation protein products, nitric oxide) and lower antioxidant enzymatic activities and glutathione concentration compared to other groups (p<0.05). Global modification of redox indices showed that more than 80% of studied individuals in acute conditions had simultaneous detrimental differences compared to a healthy status. The discriminant analysis permitted obtaining two canonical functions (p< 0.05) that reflect 98% of redox variables with 95% of variances with successful case classifications.

Conclusions: These results corroborate that oxidative stress occurred in different COVID-19 and post-acute conditions with different molecular alterations of redox indices. Redox diagnosis should be considered in early diagnosis and treatment of infection, which would be worthwhile to conduct a more comprehensive study and management of disease evolution.

Keywords: antioxidant status; COVID-19; oxidative stress; oxidative damage; SARS-CoV-2.

Resumen

Contexto: El COVID-19 relacionado con la infección por SARS-CoV-2 genera inflamación con aumento de la producción de especies reactivas del oxígeno. El tratamiento farmacológico y otros factores podrían influir en el estrés oxidativo sistémico durante el insulto patogénico.

Objetivos: Determinar el estado redox en pacientes con COVID-19 con diferentes condiciones clínicas y explorar la relación entre las variables redox y hemoquímicas.

Métodos: En este estudio longitudinal comparativo, se extrajeron muestras de sangre de 160 individuos divididos en cuatro grupos: COVID-19 asintomáticos, COVID-19 sintomáticos (síntomas bajos y moderados), COVID-19 convalecientes y sujetos presuntamente sanos. Se evaluaron los índices demográficos, redox, hematológicos y hemoquímicos. Los análisis estadísticos compararon los valores medios de cada variable y exploraron las alteraciones en los índices individuales, simultáneos y multivariadas.

Resultados: En relación con el grupo sano, los grupos COVID-19 agudo y convaleciente presentaron diferencias significativas en los índices de daño global y en el estado antioxidante (p<0,05). El grupo convaleciente mostró un daño significativamente mayor (malondialdehído, productos proteicos de oxidación avanzada, óxido nítrico) y menores actividades enzimáticas antioxidantes y concentración de glutatión en comparación con los otros grupos (p<0,05). La modificación global de los índices redox mostró que más del 80% de los individuos estudiados tenían diferencias perjudiciales simultáneas en comparación con el estado saludable. El análisis discriminante permitió obtener dos funciones canónicas (p< 0,05) que reflejan el 98% de las variables redox con el 95% de las varianzas con clasificaciones de casos acertadas.

Conclusiones: Estos resultados corroboran que el estrés oxidativo se presentó en diferentes COVID-19 y condiciones post-agudas con diferentes alteraciones moleculares de los índices redox. El diagnóstico redox debe ser considerado en el diagnóstico y tratamiento precoz de la infección, lo que valdría la pena para realizar un estudio y manejo más exhaustivo de la evolución de la enfermedad.

Palabras Clave: daño oxidativo; COVID-19; estado antioxidante; estrés oxidativo; SARS-CoV-2.

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Citation Format: Gil-del Valle L, Gravier-Hernández R, Delgado-Guerra MM, Sánchez-Márquez JA, López-Fernández OE, Acosta-Suárez MA, Rosell-Guerra T, Suárez-Iznaga R, Martínez-Casanueva R, Zamora-Rodriguez Z, Fernández-García LA, Bermudez-Alfonso Y, Hernández-Gonzalez-Abreu MC, Garrido G (2023) Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients. J Pharm Pharmacogn Res 11(1): 63–75. https://doi.org/10.56499/jppres22.1535_11.1.63
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Effect of propolis on epirubicin-induced toxicity

Pharmaceutical Science, , , ,

J Pharm Pharmacogn Res 9(4): 549-562, 2021.

Original article

Protective effect of propolis from Tigzirt on epirubicin-induced cardiotoxicity and nephrotoxicity

[Efecto protector del propóleo de Tigzirt sobre la cardiotoxicidad y nefrotoxicidad inducidas por epirrubicina]

Sara Chaa1, Mokhtaria Yasmina Boufadi1,2*, Soumia Keddari1, Amina Hayat Benchaib3

1Faculty of Natural Sciences and Life, Université de Abdelhamid Ibn Badis, Mostaganem, Algeria.

2Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.

3Laboratory of Anatomy Pathology, Public Hospital Institution of Mostaganem, Algeria.

*E-mail: yasmina.boufadi@univ-mosta.dz, yasminaboufadi@yahoo.fr

Abstract

Context: Epirubicin (EPI), belonging to the anthracycline family, is one of the most effective chemo-therapeutic agents used in the treatment of a variety of solid and hematologic malignant tumors but Its anti-tumor efficacy is dose-dependent, but its clinical use is limited by the development of cardiac, hepatic and nephrotic toxicities.

Aims: To evaluate the protective effect of ethyl acetate extract of propolis (EAP) native to Tigzirt on selected antioxidant status parameters and biomarkers of epirubicin-induced cardiotoxicity and nephrotoxicity in rats.

Methods: Thirty male Wistar albino rats were divided into five groups. It orally dosed with (EAP) or quercetin during 15 days before being subjected to toxicity by injection (i.v) of a cumulative dose of 9 mg/kg of epirubicin to repair cardiac and renal damage.

Results: Injection of epirubicin to rats induced cardiac and renal dysfunction as evidenced by a significant increase (P<0.05) in serum levels of biochemical markers (CKmb, BNP, LDH, troponin, urea, creatinine and uric acid). This toxicity thus caused lesions, necrosis, and inflammatory infiltrate in the heart and kidneys. The administration of 250 mg/kg of EAP allowed restoring these functions by lowering the level of these parameters. Thus, a balance of oxidative stress was demonstrated with a decrease of +50% in the level of malondialdehyde and nitric oxide and an increase in superoxide dismutase, catalase and glutathione peroxidase. Therefore, significant restoration was observed on organ architecture.

Conclusions: These results show that propolis is rich in phenolic substances, which gave the protective and curative effects against epirubicin-induced cardiotoxicity and nephrotoxicity in Wistar rats.

Keywords: cardiotoxicity; epirubicin; nephrotoxicity; oxidative stress; propolis.

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Resumen

Contexto: La epirrubicina (EPI), que pertenece a la familia de las antraciclinas, es uno de los agentes quimioterapéuticos más eficaces utilizados en el tratamiento de una variedad de tumores malignos sólidos y hematológicos, pero su eficacia antitumoral depende de la dosis, pero su uso clínico es limitado por el desarrollo de toxicidades cardíacas, hepáticas y nefróticas.

Objetivos: Evaluar el efecto protector del extracto de acetato de etilo de propóleo (EAP) nativo de Tigzirt sobre parámetros seleccionados del estado antioxidante y biomarcadores de cardiotoxicidad y nefrotoxicidad inducida por epirrubicina en ratas.

Métodos: Treinta ratas albinas Wistar macho fueron divididas en cinco grupos. Se dosificó por vía oral con (EAP) o quercetina durante 15 días antes de ser sometido a toxicidad por inyección (i.v) de una dosis acumulada de 9 mg/kg de epirrubicina para reparar el daño cardíaco y renal.

Resultados: La inyección de epirrubicina a ratas indujo disfunción cardíaca y renal evidenciada por un aumento significativo (p<0.05) en los niveles séricos de marcadores bioquímicos (CKmb, BNP, LDH, troponina, urea, creatinina y ácido úrico). Esta toxicidad provocó así lesiones, necrosis e infiltrados inflamatorios en el corazón y los riñones. La administración de 250 mg/kg de EAP permitió restaurar estas funciones al disminuir el nivel de estos parámetros, por lo que se demostró un equilibrio del estrés oxidativo con una disminución de +50% en el nivel de malondialdehído y óxido nítrico, y un aumento de superóxido dismutasa, catalasa y glutatión peroxidasa. Por lo tanto, se observó una restauración significativa en la arquitectura del órgano.

Conclusiones: Estos resultados muestran que el propóleo es rico en sustancias fenólicas que dieron efectos protectores y curativos contra la cardiotoxicidad y nefrotoxicidad inducida por epirrubicina en ratas Wistar.

Palabras Clave: cardiotoxicidad; epirrubicina; estrés oxidativo; nefrotoxicidad; propóleos.

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Citation Format: Chaa S, Boufadi MY, Keddari S, Benchaib AH (2021) Protective effect of propolis from Tigzirt on epirubicin-induced cardiotoxicity and nephrotoxicity. J Pharm Pharmacogn Res 9(4): 549–562.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Melatonin and quercetin versus celecoxib-induced liver damage

Pharmaceutical Science, , , , , ,


J Pharm Pharmacogn Res 9(4): 397-408, 2021.

Original article

Molecular target mechanisms of celecoxibinduced liver damage in rats and the potential prophylactic roles of melatonin and/or quercetin

[Mecanismos diana moleculares del daño hepático inducido por celecoxib en ratas y las posibles funciones profilácticas de la melatonina y/o quercetina]

Emtenan Sami Sulimani1, Jehad Mustafa Yousef2, Azza M. Mohamed2,3*

1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

2Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.

3 Department of Therapeutic Chemistry, National Research Center, Cairo, Egypt.

*E-mail: amhassan@uj.edu.sa

Abstract

Context: Celecoxib (Cele), a nonsteroidal anti-inflammatory drug (NSAID) is linked with a spectrum of hepatotoxic influences, however the underlying mechanism (s) by which this drug induces liver damage is still unexplored.

Aims: To demonstrate the hepatotoxic mechanism (s) of Cele in rats and the prophylactic roles of melatonin (Mel) and/or quercetin(Qr).

Methods: Rats were divided into eight groups, GI, served as control group; GII, Mel (12 mg/kg/day) treated group; GIII, Qr (10 mg/kg/day) treated group; GIV, Mel and Qr treated group; GV, Cele (50 mg/kg/day) treated group; GVI, Cele treated group concurrently with Mel GVII, Cele treated group concurrently with Qr; GVIII, Cele treated group concurrently with the combination of the two agents. The efficiency of Mel and/or Qr on hepatic histomorphology was also investigated.

Results: Cele significantly reduced hepatic succinate dehydrogenase and adenosine triphosphate and increased adenosine diphosphate versus the control group. Cele also caused rising in hepatic malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, caspase-3 and hydroxyproline as well as DNA damage along with depletion in catalase and glutathione reductase. Alteration in serum liver function markers and its histologic architecture were also observed in Cele treated group. Co-treatment of Cele treated rats with Mel and/or Qr, effectively ameliorated the deteriorations in the studied parameters as well as the histomorphologic liver pictures.

Conclusions: Mel and/or Qr could protect the liver from Cele, toxicity, which was more pronounced in rats treated with the combination of the two agents.

Keywords: celecoxib; inflammation; liver; melatonin; oxidative stress; quercetin.

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Resumen

Contexto: Celecoxib (Cele), un fármaco antiinflamatorio no esteroideo (AINE) está vinculado con un espectro de influencias hepatotóxicas; sin embargo, el mecanismo o mecanismos subyacentes por los que este fármaco induce daño hepático aún no se ha explorado.

Objetivos: Demostrar los mecanismos hepatotóxicos de Cele en ratas y las funciones profilácticas de melatonina (Mel) y/o quercetina (Qr).

Métodos: Las ratas se dividieron en ocho grupos, GI, sirvió como grupo control; Grupo tratado con GII, Mel (12 mg/kg/día); Grupo tratado con GIII, Qr (10 mg/kg/día); Grupo tratado con GIV, Mel y Qr; Grupo tratado con GV, Cele (50 mg/kg/día); GVI, grupo tratado con Cele al mismo tiempo que Mel GVII, grupo tratado con Cele al mismo tiempo que Qr; GVIII, grupo tratado con Cele al mismo tiempo que la combinación de los dos agentes. También se investigó la eficacia de Mel y/o Qr en la histomorfología hepática.

Resultados: Cele redujo significativamente la succinato deshidrogenasa hepática y el trifosfato de adenosina y aumentó el difosfato de adenosina en comparación con el grupo de control. Cele también provocó un aumento de malondialdehído hepático, óxido nítrico, factor de necrosis tumoral α, factor de crecimiento transformante β, caspasa 3 e hidroxiprolina, así como daño en el ADN junto con el agotamiento de la catalasa y la glutatión reductasa. También se observaron alteraciones en los marcadores de función hepática en suero y su arquitectura histológica en el grupo tratado con Cele. El tratamiento conjunto de ratas tratadas con Cele con Mel y/o Qr mejoró eficazmente el deterioro de los parámetros estudiados, así como las imágenes histomorfológicas del hígado.

Conclusiones: Mel y/o Qr podrían proteger al hígado de la toxicidad de Cele, que fue más pronunciada en ratas tratadas con la combinación de los dos agentes.

Palabras Clave: celecoxib; estrés oxidativo; hígado; inflamación; melatonina; quercetina.

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Citation Format: Sulimani ES, Yousef JM, Mohamed AM (2021) Molecular target mechanisms of celecoxib induced liver damage in rats and the potential prophylactic roles of melatonin and/or quercetin. J Pharm Pharmacogn Res 9(4): 397–408.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Effect of GSH on human epithelial cells

Pharmaceutical Science, , , , , ,

J Pharm Pharmacogn Res 9(2): 175-181, 2021.

Original Article

The role of reduced glutathione on oxidative stress, reticulum endoplasmic stress and glycation in human lens epithelial cell culture

[Papel del glutatión reducido sobre el estrés oxidativo, el estrés endoplásmico del retículo y la glicación en el cultivo de células epiteliales del cristalino humano]

Nina Handayani1*, Nur Permatasari2, Hidayat Sujuti3, Achmad Rudijanto4

1Department of Ophthalmology, Faculty of Medicine, Brawijaya University, Saiful Anwar Hospital Malang, Malang 65145, Indonesia.

2Department of Pharmacology, Faculty of Medicine, Brawijaya University, Malang 65145, Indonesia.

3Department of Biochemistry and Molecular Biology, Faculty of Medicine, Brawijaya University, Malang 65145, Indonesia.

4Division of Endocrinology and Metabolic Disease, Department of Internal Medicine, Faculty of Medicine, Brawijaya University, Saiful Anwar Hospital Malang, Malang 65145, Indonesia.

*E-mail: nina_handayani@ub.ac.id, ninahdyn@gmail.com

Abstract

Context: Cataracts are currently the main cause of blindness worldwide. This condition caused by a low concentration of reduced glutathione (GSH) in the lens.

Aims: To evaluate the effect of glutathione (GSH) on the hyperglycemia-induced oxidative stress, reticulum endoplasmic stress, and glycation in human lens epithelial cells.

Methods: Human lens epithelial cells were cultured under high-glucose conditions. Malondialdehyde (MDA), protein carbonyl content (PCC), glucose reactive protein (GRP), and advanced glycation end product (AGE) were measured by enzyme-linked immunosorbent assay after 72 h of incubation for MDA, PCC, GRP and after 2 weeks incubation for AGE.

Results: The MDA and PCC levels increased in response to high-dose glucose administration compared to the control group.  MDA and PCC levels were decreased at all GSH doses, whereas the lowest mean MDA and PCC levels were observed at GSH doses of 10 and 100 μM, respectively.  GRP levels increased after high-glucose administration as compared to the control group. Additionally, the groups co-treated with 30 and 100 μM GSH showed reduced PCC. The AGE level was reduced at all doses of GSH compared to those in the control group.

Conclusions: The results suggest that GSH inhibits oxidative stress, reticulum endoplasmic stress, and AGE formation, which may lead to the progression of diabetic cataract. Additionally, GSH may maintain lens transparency by acting as an antiglycation and controlling the AGE formation.

Keywords: glycation; glutathione; glucose reactive protein; hyperglycemia; malondialdehyde; oxidative stress.

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Resumen

Contexto: Las cataratas son actualmente la principal causa de ceguera en todo el mundo. Esta condición es causada por una baja concentración de glutatión reducido (GSH) en el cristalino.

Objetivos: Evaluar el efecto del glutatión (GSH) sobre el estrés oxidativo inducido por la hiperglucemia, el estrés endoplásmico del retículo y la glicación en las células epiteliales del cristalino humano.

Métodos: Se cultivaron células epiteliales del cristalino humano en condiciones de alto contenido de glucosa. El malondialdehído (MDA), el contenido de carbonilo proteico (PCC), la proteína reactiva a la glucosa (GRP) y el producto final de glicación avanzada (AGE) se midieron mediante un ensayo inmunoabsorbente ligado a enzimas después de 72 h de incubación para MDA, PCC, GRP y después de 2 semanas incubación para AGE.

Resultados: Los niveles de MDA y PCC aumentaron en respuesta a la administración de glucosa en dosis altas en comparación con el grupo de control. Los niveles de MDA y PCC disminuyeron en todas las dosis de GSH, mientras que los niveles medios más bajos de MDA y PCC se observaron en dosis de GSH de 10 y 100 μM, respectivamente. Los niveles de GRP aumentaron después de la administración de glucosa alta en comparación con el grupo control. Además, los grupos tratados conjuntamente con 30 y 100 µM de GSH mostraron una reducción del PCC. El nivel de AGE se redujo en todas las dosis de GSH en comparación con las del grupo de control.

Conclusiones: Los resultados sugieren que GSH inhibe el estrés oxidativo, el estrés endoplásmico del retículo y la formación de AGE, lo que puede conducir a la progresión de la catarata diabética. Además, GSH puede mantener la transparencia de la lente actuando como antiglicación y controlando la formación de AGE.

Palabras Clave: estrés oxidativo; glicación; glutatión; hiperglucemia; malondialdehído; proteína reactiva a la glucosa.

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Citation Format: Handayani N, Permatasari N, Sujuti H, Rudijanto A (2021) The role of reduced glutathione on oxidative stress, reticulum endoplasmic stress and glycation in human lens epithelial cell culture. J Pharm Pharmacogn Res 9(2): 175–181.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)