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The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

Dietrich F, Pietrobon Martins J, Kaiser S, Madeira Silva RB, Rockenbach L, Albano Edelweiss MI, Ortega GG, Morrone FB, Campos MM, Battastini AM - PLoS ONE (2015)

Bottom Line: Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions.Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder.This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy.

View Article: PubMed Central - PubMed

Affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.

ABSTRACT
Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

No MeSH data available.


Related in: MedlinePlus

Effect of treatment with Mesna or QAPF from Uncaria tomentosa on the development of visceral sensitivity.The visceral sensitivity was measured by the frequency of responses to von Frey filament testing in the lower abdominal area one day before (baseline) and 1.5 h after the HE induction. Each column represents the mean of at least 8 animals, and the vertical lines show the SEM. ##p<0.01 denotes the significance levels compared to saline values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.
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pone.0131882.g002: Effect of treatment with Mesna or QAPF from Uncaria tomentosa on the development of visceral sensitivity.The visceral sensitivity was measured by the frequency of responses to von Frey filament testing in the lower abdominal area one day before (baseline) and 1.5 h after the HE induction. Each column represents the mean of at least 8 animals, and the vertical lines show the SEM. ##p<0.01 denotes the significance levels compared to saline values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.

Mentions: To confirm the effects of QAPF on nociception, we evaluated visceral sensitivity using von Frey filaments. Fig 2 summarizes the frequency of responses to von Frey filament stimulation of the lower abdominal area one day before and 1.5 h after HE induction. We observed that after the injection of CYP, mice became more sensitive to the filament and the response frequency reached almost 50% using a 0.4 g von Frey filament. Moreover, mice treated with QAPF presented a similar profile regarding behavior nociceptive score (Fig 1B) and visceral sensitivity (Fig 2) when compared to CYP-mice, suggesting that QAPF was able to inhibit hypersensitivity in the pelvic area, which may lead to reduced abdominal discomfort and/or pelvic pain. Furthermore, none of the treatments produced significant changes in locomotor parameters in the open-field arena (S1 Fig).


The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

Dietrich F, Pietrobon Martins J, Kaiser S, Madeira Silva RB, Rockenbach L, Albano Edelweiss MI, Ortega GG, Morrone FB, Campos MM, Battastini AM - PLoS ONE (2015)

Effect of treatment with Mesna or QAPF from Uncaria tomentosa on the development of visceral sensitivity.The visceral sensitivity was measured by the frequency of responses to von Frey filament testing in the lower abdominal area one day before (baseline) and 1.5 h after the HE induction. Each column represents the mean of at least 8 animals, and the vertical lines show the SEM. ##p<0.01 denotes the significance levels compared to saline values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496084&req=5

pone.0131882.g002: Effect of treatment with Mesna or QAPF from Uncaria tomentosa on the development of visceral sensitivity.The visceral sensitivity was measured by the frequency of responses to von Frey filament testing in the lower abdominal area one day before (baseline) and 1.5 h after the HE induction. Each column represents the mean of at least 8 animals, and the vertical lines show the SEM. ##p<0.01 denotes the significance levels compared to saline values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.
Mentions: To confirm the effects of QAPF on nociception, we evaluated visceral sensitivity using von Frey filaments. Fig 2 summarizes the frequency of responses to von Frey filament stimulation of the lower abdominal area one day before and 1.5 h after HE induction. We observed that after the injection of CYP, mice became more sensitive to the filament and the response frequency reached almost 50% using a 0.4 g von Frey filament. Moreover, mice treated with QAPF presented a similar profile regarding behavior nociceptive score (Fig 1B) and visceral sensitivity (Fig 2) when compared to CYP-mice, suggesting that QAPF was able to inhibit hypersensitivity in the pelvic area, which may lead to reduced abdominal discomfort and/or pelvic pain. Furthermore, none of the treatments produced significant changes in locomotor parameters in the open-field arena (S1 Fig).

Bottom Line: Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions.Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder.This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy.

View Article: PubMed Central - PubMed

Affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.

ABSTRACT
Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

No MeSH data available.


Related in: MedlinePlus