Category Archives: Hepatotoxicity

Effect of mouse sex on pharmacological investigations

J. Pharm. Pharmacogn. Res., vol. 8, no. 6, pp. 569-579, November-December 2020.


Original Article

Effect of sex differences in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal activities in mice model

[Efecto de las diferencias sexuales en las actividades antinociceptiva, antipirética, hipoglucemia, hepatoprotectora y antidiarreica en modelo de ratones]

Irin Karim#, Roni Roy#, Md Rafiul Hoque, Sazzad Hosen, Tanaya Bhowmik, Israt Jahan Liya, Afroza Akter, Mohammad Anwarul Basher

Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali-3814, Bangladesh.
#These two authors contributed equally.


Context: The use of animal models is a longstanding practice in biological research. Among different models, the mouse is the most widely used and accepted model. In designing the mouse model, a male mouse is generally preferred over a female to avoid the effect of changing hormonal state in females. However, it is not known whether mouse sex affects all experiments.

Aims: To determine the effect of mouse sex on pharmacological responses in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal experiments.

Methods: Antinociceptive study was performed by three different experiments. An antipyretic experiment was performed by yeast induced hyperthermia test. The effect on hypoglycemic response was assessed by an oral glucose tolerance test. The effect on the hepatoprotective study was evaluated by carbon tetrachloride-induced liver damage. The antidiarrheal study was conducted by a castor oil-induced diarrhea test.

Results: Antinociceptive studies demonstrated mixed effects. Hot plate test showed significant differences; the licking test showed variation only in the late phase, while no significant variation was observed. In the antipyretic experiment, female mice showed higher body temperature in both control and standard that varied significantly with male mice. Hypoglycemia and hepatoprotective tests did not show significant variation between sexes; however, liver enzymes levels were found higher in males while the percentage liver weight was higher in females. In the antidiarrheal test, the male mouse was observed to have higher responses than the female.

Conclusions: Antinociceptive and antipyretic investigations should be performed separately on both male and female mice. On the other hand, hypoglycemic, hepatoprotective and antidiarrheal tests can be conducted on any mouse sex, and findings on particular sex can be extrapolated to the opposite sex.

Keywords: drug discovery; sex dimorphism; Swiss albino mice.


Contexto: El uso de modelos animales es una práctica de larga data en la investigación biológica. Entre los diferentes modelos, el ratón es el modelo más utilizado y aceptado. Al diseñar el modelo de ratón, generalmente se prefiere un ratón macho a una hembra para evitar el efecto del cambio de estado hormonal en las hembras. Sin embargo, no se sabe si el sexo del ratón afecta a todos los experimentos.

Objetivos: Determinar el efecto del sexo del ratón sobre las respuestas farmacológicas en experimentos antinociceptivos, antipiréticos, hipoglucémicos, hepatoprotectores y antidiarreicos.

Métodos: Se realizaron experimentos para demostrar efectos anti-nociceptivo (tres experimentos diferentes), antipirético (hipertermia inducida por levaduras), hipoglucémico (prueba de tolerancia a la glucosa oral), hepatoprotector (daño hepático inducido por tetracloruro de carbono) y antidiarreico (diarrea inducida por aceite de ricino).

Resultados: Los estudios antinociceptivos demostraron efectos mixtos. La prueba de la placa caliente mostró diferencias significativas; la prueba de lamido mostró variación solo en la fase tardía, mientras que no se observó variación significativa. En el experimento antipirético, las hembras mostraron una temperatura corporal más alta tanto en el control como en el estándar que varió significativamente con los ratones machos. Las pruebas de hipoglucemia y hepatoprotección no mostraron variación significativa entre sexos; sin embargo, los niveles de enzimas hepáticas se encontraron más altos en los machos mientras que el porcentaje de peso del hígado fue más alto en las hembras. En la prueba antidiarreica, se observó que el ratón macho tenía respuestas más altas que la hembra.

Conclusiones: Las investigaciones antinociceptivas y antipiréticas debían realizarse por separado en ratones machos y hembras. Por otro lado, las pruebas hipoglucémicas, hepatoprotectoras y antidiarreicas podrían realizarse en cualquier sexo de ratón, y los hallazgos sobre un sexo particular se pueden extrapolar al sexo opuesto.

Palabras Clave: dimorfismo sexual; investigación en medicamento; ratones albinos suizos.

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Citation Format: Karim I, Roy R, Hoque MR, Hosen S, Bhowmik T, Liya IJ, Akter A, Basher MA (2020) Effect of sex differences in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal activities in mice model. J Pharm Pharmacogn Res 8(6): 569–579. DOI:

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© 2020 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Hepatoprotective activity of Cordia sebestena fruit

J Pharm Pharmacogn Res 8(4): 327-335, 2020.


Original Article

Hepatoprotective response of Cordia sebestena L. fruit against simvastatin induced hepatotoxicity

[Respuesta hepatoprotectora de la fruta de Cordia sebestena contra la hepatotoxicidad inducida por simvastatina]

Sachin Chaudhary1*, Ramesh Kumar Gupta3, Mandeep Kumar Gupta3, Harish Chandra Verma3, Hitesh Kumar3, Amit Kumar4, Sudhansu Ranjan Swain3, Abdel-Nasser El-Shorbagi1,2

1Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah-27272, United Arab Emirates.
2Faculty of Pharmacy, University of Assiut, Assiut-71526, Egypt.
3Moradabad Educational Trust, Group of Institutions, Faculty of Pharmacy, Moradabad-244001, Uttar Pradesh, India.
4School of Pharmaceutical Sciences, IIMT University, Meerut-250002, Uttar Pradesh, India.

Context: Cordia sebestena fruits are traditionally used to treat wounds, boils, tumors, gout, ulcer, flu, fever, asthma, menstrual cramps, dysentery, diarrhea, headache, snakebite and liver disorders. However, information on hepatoprotective potential of Cordia sebestena fruit has not been reported in the research.

Aims: To evaluate the hepatoprotective effect of the ethanolic extract of Cordia sebestena fruit (CSFE) against simvastatin-induced hepatotoxicity in rats.

Methods: After authentication of fruit, its ethanolic extract was collected. Hepatotoxicity was induced by simvastatin in rodents. Hepatoprotective potential of CSFE was evaluated at 200 and 400 mg/kg, body weight by determining the altered levels of biochemical parameters like serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), cholesterol, bilirubin, urea, albumin, total protein and hematological indices including red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), platelets, and lymphocytes along with the impact on body and liver weight of treated rats.

Results: The treatment with CSFE at 200 mg/kg and 400 mg/kg, significantly at (p<0.05, p<0.001) and dose-dependently reversed simvastatin-induced altered level of SGOT, SGPT, cholesterol, urea, total bilirubin and restored the total protein and albumin level in rodents. Hematological indices also were significantly ameliorated at both the doses of CSFE. Histopathological study revealed the regeneration of hepatocytes.

Conclusions: The Cordia sebestena fruit extract (CSFE) at dose of 400 mg/kg reversed liver deteriorations induced by simvastatin in rats, therefore manifesting its traditional use as hepatoprotector. Future studies should be performed for isolating biologically active phytoconstituents.

Keywords: cholesterol; Cordia sebestena; hepatotoxicity; serum glutamic oxaloacetic transaminase; serum glutamic pyruvic transaminase; simvastatin.


Contexto: Las frutas de Cordia sebestena se utilizan tradicionalmente para tratar heridas, forúnculos, tumores, gota, úlcera, gripe, fiebre, asma, calambres menstruales, disentería, diarrea, dolor de cabeza, mordedura de serpiente y trastornos hepáticos. Sin embargo, no se ha investigado sobre el potencial hepatoprotector de esta fruta.

Objetivos: Evaluar el efecto hepatoprotector del extracto etanólico de fruta de Cordia sebestena (CSFE) contra la hepatotoxicidad inducida por simvastatina en ratas.

Métodos: Después de la autenticación de la fruta, se realizó su extracto etanólico. La hepatotoxicidad fue inducida por simvastatina en roedores. El potencial hepatoprotector de CSFE se evaluó a 200 y 400 mg/kg, peso corporal determinando los niveles alterados de parámetros bioquímicos como transaminasa oxaloacética glutámica sérica (SGOT), transaminasa piruvica glutámica sérica (SGPT), colesterol, bilirrubina, urea, albúmina, proteína total e índices hematológicos, incluidos los glóbulos rojos (RBC), glóbulos blancos (WBC), hemoglobina (Hb), plaquetas y linfocitos, junto con el impacto en el peso corporal y hepático de las ratas tratadas.

Resultados: El tratamiento con CSFE a 200 mg/kg y 400 mg/kg, revertió significativamente, y de manera dependiente de la dosis, los niveles alterados de SGOT, SGPT, colesterol, urea, bilirrubina total inducidos por simvastatina, restaurado los niveles totales de proteína y albúmina en roedores. Los índices hematológicos también mejoraron significativamente (p<0.05, p<0.001) en ambas dosis de CSFE. El estudio histopatológico reveló la regeneración de los hepatocitos.

Conclusiones: El extracto de fruta de Cordia sebestena (CSFE) a una dosis de 400 mg/kg protegió del deterioro hepático inducido por simvastatina en ratas, manifestando así su uso tradicional como hepatoprotector. Se deben realizar estudios futuros para aislar fitoconstituyentes biológicamente activos.

Palabras Clave: colesterol; Cordia sebestena; hepatotoxicidad; transaminasa glutámica oxaloacética sérica; simvastatina; transaminasa pirúvica glutámica sérica.

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Citation Format: Chaudhary S, Gupta RK, Gupta MK, Verma HC, Kumar H, Kumar A, Swain SR, El-Shorbagi AN (2020) Hepatoprotective response of Cordia sebestena L. fruit against simvastatin induced hepatotoxicity. J Pharm Pharmacogn Res 8(4): 327–335. DOI:

© 2020 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Subchronic toxicity of the low-dose monocrotaline in rats

J Pharm Pharmacogn Res 8(4): 308-315, 2020.


Original Article

Subchronic toxicity of the pulmonary hypertension model due to low-dose monocrotaline in rats

[Toxicidad subcrónica del modelo de hipertensión pulmonar debido a dosis bajas de monocrotalina en ratas]

Vicente Benavides-Cordoba1, Melissa Silva-Medina1, María Ximena Varela2,3, Mauricio Palacios Gómez1*

1Department of Pharmacology, Basic Sciences School, Universidad del Valle. Cali, Colombia.
2Department of Pathology, Universidad del Valle. Cali, Colombia.
3Department of Pathology, Hospital Universitario del Valle. Cali, Colombia.

Context: The study of pulmonary hypertension is mainly based on an experimental model that induces this condition using monocrotaline. Even though this model has been in use for decades, the toxic effect of low dose monocrotaline in other systems is not well described.

Aims: To evaluate the renal and hepatic effects of monocrotaline in order to be able to better predict the pharmacodynamic impact that it could have.

Methods: Two groups of rats were used, the first one received monocrotaline following pulmonary hypertension protocol (30 mg/kg) and the second one received saline 0.9%. At day 60 blood from the vena cava was obtained and liver and kidney were extracted for histologic exam. Fulton index (right ventricle hypertrophy measurement) was used to confirm pulmonary hypertension.

Results: The monocrotaline group presents focal interstitial lymphoid infiltration and regeneration foci in the kidney as well as venous congestion of the liver in some of the animals, these changes were not found in the control group. Kidney and liver function tests showed no significant differences. These results show that low-dose monocrotaline model for pulmonary hypertension generates changes on liver and kidney; however, these alterations were not consistent, making it a viable model for evaluating new drugs in this condition.

Conclusions: The present study demonstrates that the low dose of monocrotaline (30 mg/kg) in animals exposed for 60 days does not cause consistent changes in liver and kidney; there were findings in some animals that could be caused by cardiovascular changes generated by pulmonary hypertension.

Keywords: animal models; monocrotaline; pulmonary hypertension; right ventricular hypertrophy, subacute toxicity.


Contexto: El estudio de la hipertensión pulmonar se basa principalmente en un modelo experimental que induce esta condición usando monocrotalina. Aunque este modelo ha estado en uso durante décadas, el efecto tóxico de las dosis bajas de monocrotalina en otros sistemas no está bien descrito.

Objetivos: Evaluar los efectos renales y hepáticos de la monocrotalina con el fin de mejorar la predicción del impacto farmacodinámico que podría tener.

Métodos: Se utilizaron dos grupos de ratas, el primero recibió monocrotalina siguiendo el protocolo de hipertensión pulmonar (30 mg/kg) y el segundo recibió solución salina al 0.9%. En el día 60 se obtuvo sangre de la vena cava y se extrajeron hígado y riñón para examen histológico. Se utilizó el índice de Fulton (medición de hipertrofia del ventrículo derecho) para confirmar la hipertensión pulmonar.

Resultados: El grupo de monocrotalina tuvo focos de infiltración linfoide intersticial focal y focos de regeneración en el riñón, así como congestión venosa del hígado en algunos de los animales, estos cambios no se encontraron en el grupo de control. Las pruebas de función renal y hepática no mostraron diferencias significativas. Estos resultados muestran que el modelo de dosis bajas de monocrotalina para la hipertensión pulmonar genera cambios en el hígado y los riñones; sin embargo, estas alteraciones no fueron consistentes, por lo que es un modelo viable para evaluar nuevos medicamentos en esta condición.

Conclusiones: El presente estudio demuestra que la dosis baja de monocrotalina (30 mg/kg) en animales expuestos durante 60 días no ocasiona cambios consistentes en el hígado y los riñones; Hubo hallazgos en algunos animales que podrían ser causados por cambios cardiovasculares generados por la hipertensión pulmonar.

Palabras Clave: hipertensión pulmonar; hipertrofia ventricular derecha; modelos animales; monocrotalina; toxicidad subaguda.

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Citation Format: Benavides-Cordoba V, Silva-Medina M, Varela MX, Palacios Gómez M (2020) Subchronic toxicity of the pulmonary hypertension model due to low-dose monocrotaline in rats. J Pharm Pharmacogn Res 8(4): 308–315. DOI:

© 2020 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Hepatoprotective and antioxidant potential of Nyctanthes arbor-tristis L.

J Pharm Pharmacogn Res 6(3): 205-215, 2018.


Original Article

Hepatoprotective and antioxidant potential of Nyctanthes arbor-tristis L. leaves against antitubercular drugs induced hepatotoxicity

[Potencial hepatoprotector y antioxidante de hojas de Nyctanthes Arbor-tristis L. contra la hepatotoxicidad inducida por fármacos antituberculosos]

Sachin Chaudhary1, 2*, Ramesh K. Gupta2, 3, Amit Kumar4, Hamadeh Tarazi1

1College of Pharmacy, University of Sharjah, Sharjah-27272, United Arab Emirates.
2Moradabad Educational Trust Group of Institutions, Faculty of Pharmacy, Moradabad-244001, Uttar Pradesh, India.
3Sherwood College of Pharmacy, Barabanki-225001, Uttar Pradesh, India.
4College of Pharmacy, Neelkanth Group of Institutions, Meerut-250110, Uttar Pradesh, India.



Context: Nyctanthes arbor-tristis L. (Oleaceae) leaf are used in treatment of malaria, rheumatoid arthritis, chronic fever and enlargement of spleen; however, there is paucity of information on its hepatoprotective and antioxidant potential.

Aims: To evaluate hepatoprotective and antioxidant potentials of ethanolic leaf extract of Nyctanthes arbor-tristis L.

Methods: After collection and authentication of the vegetal material, ethanolic extract was collected. The combination of antitubercular drugs (isoniazid, rifampicin and pyrazinamide) was used to induce hepatotoxicity in Wistar rats. Hepatoprotective effect was evaluated at doses 125, 250 and 500 mg/kg, body weight by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects on lipid peroxidation (LPO), reduced glutathione (GSH) and catalase (CAT), superoxide dismutase (SOD) were estimated. Docking study was conducted to anticipate the probable biological targets associated with its hepatoprotective effect.

Results: The plant extract dose of 500 mg/kg, body weight significantly declined the levels of AST, ALT, ALP and TBL at (p < 0.001), which is approximately corresponding to the dose of reference compound silymarin and reversed the levels of LPO, GSH, SOD, CAT as compared to silymarin dose. Histopathological studies revealed regeneration of hepatocytes. The docking results suggested that some active constituents of plant leaves potentially interact with human pregnane X receptor, human constitutive androstane receptor and the farnesoid X receptor.

Conclusions: The extract of Nyctanthes arbor-tristis L. remarkably possesses hepatoprotective and antioxidant effect and evinced its traditional claim. Future studies should be done to isolate active phytoconstituents for use in drug discovery.

Keywords: antioxidant; docking; hepatoprotective; Nyctanthes arbor-tristis.


Contexto: Las hojas de Nyctanthes arbor-tristis L. (Oleaceae) se utilizan en el tratamiento de la malaria, artritis reumatoide, la fiebre crónica y el bazo agrandado; sin embargo, existe escasez de información sobre su potencial hepatoprotector y antioxidante.

Objetivos: Evaluar el potencial hepatoprotector y antioxidante del extracto etanol de hoja de Nyctanthes arbor-tristis L.

Métodos: Después de la colección y la autenticación del material vegetal fue realizado el extracto etanólico. La combinación de fármacos antituberculosos (isoniacida, rifampicina y pirazinamida) fue utilizada para inducir hepatotoxicidad en ratas de Wistar. El efecto hepatoprotector se evaluó en dosis 125, 250 y 500 mg/kg de peso corporal mediante la estimación de la actividad de alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), fosfatasa alcalina (ALP) y los niveles de bilirrubina total (TBL). Se estimaron los efectos sobre la peroxidación lipídica (LPO), glutatión reducido (GSH), catalasa (CAT), y superóxido dismutasa (SOD). Además, se llevó a cabo un estudio de acoplamiento para anticipar los probables blancos biológicos asociados con su efecto hepatoprotector.

Resultados: La dosis de 500 mg/kg de extracto de planta disminuyó significativamente los niveles de AST, ALT, ALP y TBL (p < 0.001), que se corresponde aproximadamente a la dosis del compuesto referencia silimarina y revertió los niveles de LPO, GSH, SOD, CAT, en comparación con la dosis de silimarina. Los estudios histopatológicos revelaron regeneración de hepatocitos. Los resultados del acoplamiento sugirieron que algunos componentes activos de las hojas de la planta potencialmente interactuarán con el receptor X de pregnano humano, el receptor androstane constitutivo humano y el receptor de farnesoid X.

Conclusiones: El extracto de Nyctanthes arbor-tristis L. posee efecto hepatoprotector y antioxidante notable y valida su uso tradicional. Estudios futuros deben llevarse a cabo para aislar fitoconstituyentes activos para su uso en el descubrimiento de medicamentos.

Palabras Clave: antioxidantes; antituberculosos; hepatoprotector; Nyctanthes arbor-tristis.

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Citation Format: Chaudhary S, Gupta RK, Kumar A, Tarazi H (2018) Hepatoprotective and antioxidant potential of Nyctanthes arbor-tristis L. leaves against antitubercular drugs induced hepatotoxicity. J Pharm Pharmacogn Res 6(3): 205–215. DOI:

© 2018 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Hepatotoxic effect of nevirapine in juvenile albino rats

J Pharm Pharmacogn Res 5(4): 217-226, 2017.


Original Article

Possible hepatotoxic consequence of nevirapine use in juvenile albino rats

[Posible consecuencia hepatotóxica del uso de nevirapina en ratas albinas juveniles]

Elias Adikwu1, Bonsome Bokolo2

1Department of Pharmacology, Faculty of Basic Medical Sciences, University of Port Harcourt, Choba, Rivers State, Nigeria.
2Department of Pharmacology, Faculty of Basic Medical Sciences, Niger Delta University Wilberforce Island, Bayelsa State, Nigeria.



Context: Nevirapine (NVP) is used in human immunodeficiency virus exposed neonates. This could present safety concern due to decreased liver metabolizing enzymes activity and renal clearance in neonates.

Aims: To determine the hepatotoxic effect of NVP in juvenile albino rats.

Methods: Juvenile albino rats were weighed, divided into groups and treated orally with 4-32 mg/kg/day of NVP for 14 days including a recovery group. The control groups were treated with water (placebo) and normal saline (solvent). At the end of NVP treatment, rats were weighed and sacrificed, blood was collected and serum extracted. Serum was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB) and conjugated bilirubin (CB). The liver was harvested via dissection, weighed and evaluated for AST, ALT, ALP, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA) levels and histological damage.

Results: The body, absolute and relative liver weights of rats in NVP treated groups were not significantly different (p>0.05) when compared to placebo. However, serum levels of AST, ALT, ALP, TB and CB were significantly increased (p<0.05) in a dose-dependent manner in NVP-treated groups. Furthermore, liver levels of ALT, ALP, AST and MDA were significantly increased (p<0.05) while SOD, CAT, and GSH were decreased in a dose dependent manner in NVP-treated groups. NVP-treated rats were characterized by varying degrees of hepatic morphological alterations. However, in the recovery group, the effects of NVP were reversed.

Conclusions: This study observed dose-dependent and reversible hepatotoxicity in nevirapine- treated juvenile albino rats.

Keywords: juvenile rats; liver; nevirapine; oxidative stress; toxicity.


Contexto: La nevirapina (NVP) se utiliza en los recién nacidos expuestos al virus de inmunodeficiencia humana. Esta podría presentar problemas de seguridad debido a la disminución de la actividad enzimática del metabolismo hepático y la depuración renal en los recién nacidos.

Objetivos: Determinar el efecto hepatotóxico de NVP en ratas albinas juveniles.

Métodos: Se pesaron ratas albinas juveniles, se dividieron en grupos y se trataron oralmente con 4-32 mg/kg/día de NVP durante 14 días, incluyendo un grupo de recuperación. Los grupos controles se trataron con agua (placebo) y solución salina normal (disolvente). Al final del tratamiento con NVP, las ratas fueron pesadas y sacrificadas, se recogió sangre y se extrajo el suero. El suero se analizó para la determinación de alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), fosfatasa alcalina (ALP), bilirrubina total (TB) y bilirrubina conjugada (CB). Los hígados fueron extraídos, pesados y evaluados los niveles de AST, ALT, ALP, superóxido dismutasa (SOD), catalasa (CAT), glutatión (GSH), malondialdehído (MDA) y daño histológico.

Resultados: Los pesos corporal, absolutos y relativos del hígado en los grupos tratados con NVP no fueron significativamente diferentes (p> 0.05) en comparación con el placebo. Sin embargo, los niveles séricos de AST, ALT, ALP, TB y CB aumentaron de forma dependiente de la dosis en los grupos tratados con NVP (p <0,05). Además, los niveles hepáticos de ALT, ALP, AST y MDA se incrementaron mientras que SOD, CAT y GSH disminuyeron de forma dependiente de la dosis en grupos tratados con NVP (p<0,05). Las ratas tratadas con NVP mostraron varios grados de alteraciones morfológicas hepáticas. Sin embargo, en el grupo de recuperación, los efectos de la NVP fueron revertidos.

Conclusiones: Este estudio observó una hepatotoxicidad dependiente de la dosis y reversible en ratas albinas juveniles tratadas con nevirapina.

Palabras Clave: estrés oxidativo; hígado; nevirapina; ratas juveniles; toxicidad.

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Citation Format: Adikwu E, Bokolo B (2017) Possible hepatotoxic consequence of nevirapine use in juvenile albino rats. J Pharm Pharmacogn Res 5(4): 217–226. DOI:

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)